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1.
Dig Dis Sci ; 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38949750

RESUMEN

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.

2.
J Colloid Interface Sci ; 675: 84-93, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38964127

RESUMEN

In this study, we innovatively synthesized nitrogen-doped carbon microspheres (NCS) derived from oatmeal. By utilizing polyoxometalates (POM) as both reducing and linking agents, we achieved uniform loading of platinum nanoparticles (Pt NPs) onto the surface of the NCS. The composite nanoparticles constructed from Pt/polyoxometalate/nitrogen-doped carbon microspheres (Pt/POM/NCS) fully exploit the synergistic catalytic effect, demonstrating superior performance in adrenaline detection. The method has a linear range of 2.59 to 1109.59 µM, a detection limit as low as 0.25 µM (S/N = 3), and a sensitivity of 0.74 µA µM-1 cm-2. Additionally, it exhibits high stability and strong anti-interference ability. The recoveries in human serum were 98.51 % to 101.25 %.

3.
Ann Acad Med Singap ; 53(6): 371-385, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38979993

RESUMEN

Introduction: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare haematologic disease characterised by intravascular haemolysis, thrombophilia and bone marrow failure. There is a lack of established clinical guidance on the screening, diagnosis and manage-ment of PNH in Singapore. A relatively low level of awareness among healthcare professionals regarding PNH manifestations further contributes to diagnostic delays. Additionally, limited access to complement inhibitors, like eculizumab, may delay treatment and impact patient outcomes. Method: Nine haematologists from different institu-tions in Singapore convened to formulate evidence-based consensus recommendations for optimising the diagnosis and management of patients with PNH and improving access to novel treatments. The experts reviewed the existing literature and international guidelines published from January 2010 to July 2023, focusing on 7 clinical questions spanning PNH screening, diagnostic criteria, investigations, treatment and monitoring of subclinical and classic disease, PNH with underlying bone marrow disorders, and PNH in pregnancy. A total of 181 papers were reviewed to formulate the statements. All experts voted on the statements via 2 rounds of Delphi and convened for an expert panel discussion to finetune the recommendations. Results: Sixteen statements have been formulated for optimising the screening, diagnosis and management of PNH. Upon confirmation of PNH diagnosis, individuals with active haemolysis and/or thrombosis should be considered for anti-complement therapy, with eculizumab being the only approved drug in Singapore. Conclusion: The current recommendations aim to guide the clinicians in optimising the screening, diagnosis and management of PNH in Singapore.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Hemoglobinuria Paroxística , Hemoglobinuria Paroxística/diagnóstico , Hemoglobinuria Paroxística/terapia , Humanos , Singapur , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Consenso , Embarazo , Inactivadores del Complemento/uso terapéutico , Técnica Delphi , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/terapia , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Masculino
4.
Cancers (Basel) ; 16(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38893190

RESUMEN

PURPOSE: To assess the association of a polygenic risk score (PRS) for functional genetic variants with the risk of developing breast cancer. METHODS: Summary data-based Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) were used to identify breast cancer risk variants associated with gene expression and DNA methylation levels. A new SMR-based PRS was computed from the identified variants (functional PRS) and compared to an established 313-variant breast cancer PRS (GWAS PRS). The two scores were evaluated in 3560 breast cancer cases and 3383 non-cancer controls and also in a prospective study (n = 10,213) comprising 418 cases. RESULTS: We identified 149 variants showing pleiotropic association with breast cancer risk (eQTLHEIDI > 0.05 = 9, mQTLHEIDI > 0.05 = 165). The discriminatory ability of the functional PRS (AUCcontinuous [95% CI]: 0.540 [0.526 to 0.553]) was found to be lower than that of the GWAS PRS (AUCcontinuous [95% CI]: 0.609 [0.596 to 0.622]). Even when utilizing 457 distinct variants from both the functional and GWAS PRS, the combined discriminatory performance remained below that of the GWAS PRS (AUCcontinuous, combined [95% CI]: 0.561 [0.548 to 0.575]). A binary high/low-risk classification based on the 80th centile PRS in controls revealed a 6% increase in cases using the GWAS PRS compared to the functional PRS. The functional PRS identified an additional 12% of high-risk cases but also led to a 13% increase in high-risk classification among controls. Similar findings were observed in the SCHS prospective cohort, where the GWAS PRS outperformed the functional PRS, and the highest-performing PRS, a combined model, did not significantly improve over the GWAS PRS. CONCLUSIONS: While this study identified potentially functional variants associated with breast cancer risk, their inclusion did not substantially enhance the predictive accuracy of the GWAS PRS.

5.
Phys Rev Lett ; 132(23): 235001, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38905668

RESUMEN

Relativistic positron sources with high spin polarization have important applications in nuclear and particle physics and many frontier fields. However, it is challenging to produce dense polarized positrons. Here we present a simple and effective method to achieve such a positron source by directly impinging a relativistic high-density electron beam on the surface of a solid target. During the interaction, a strong return current of plasma electrons is induced and subsequently asymmetric quasistatic magnetic fields as high as megatesla are generated along the target surface. This gives rise to strong radiative spin flips and multiphoton processes, thus leading to efficient generation of copious polarized positrons. With three-dimensional particle-in-cell simulations, we demonstrate the production of a dense highly polarized multi-GeV positron beam with an average spin polarization above 40% and nC-scale charge per shot. This offers a novel route for the studies of laserless strong-field quantum electrodynamics physics and for the development of high-energy polarized positron sources.

6.
Curr Issues Mol Biol ; 46(6): 5668-5681, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38921010

RESUMEN

Based on the analgesic and anti-inflammatory effects of clonidine in previous studies, we hypothesized that clonidine could accelerate wound healing in rats by regulating the expression of related cytokines. In this study, the wound healing effect of clonidine was evaluated using an excision wound model in diabetic rats and a HaCaT cell model. The wounds were treated daily with topical clonidine. The results analyzed by ImageJ2 software show that the wounds of the rats that were treated with 15 ng/mL clonidine recovered faster, and the wound size was also significantly reduced compared to the control group. Western blot assays determined that clonidine induced an increase in the expression of vascular growth factors, namely, Ang-1, Ang-2, and VEGF. Moreover, clonidine demonstrated a rescuing effect on JAK2 within the JAK/STAT pathway by inhibiting SOCS3 expression, leading to decreased SOCS3 levels and increased expression of JAK2 and phospho-STAT3. Histopathological analysis revealed that clonidine promoted complete epithelial repair and minimized inflammation in skin tissue. Additionally, clonidine stimulated HaCaT cell proliferation in vitro and enhanced cellular energy levels in the presence of AGEs. In conclusion, clonidine promoted vascular growth and wound healing by stimulating the expression of cytokines that are beneficial for wound healing.

7.
RSC Adv ; 14(27): 19446-19458, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38919374

RESUMEN

Incomplete combustion yields a significant byproduct, known for its high toxicity to humans: gas phase carbon monoxide (CO). This study utilized several advanced theoretical methods to examine the factors contributing to the activation energy involved in CO capture by a frustrated Lewis pair (FLP) and to forecast the potential success of the CO capture reaction. The current theoretical findings indicate that among the four-membered-ring Group-13/N-FLP and B/Group-15-FLP molecules, only the B/N-based FLP-type molecule effectively captures CO, considering both thermodynamics and kinetics. According to the results obtained through energy decomposition analysis-natural orbitals for chemical valence (EDA-NOCV), it can be concluded that the donor-acceptor (singlet-singlet) model, rather than the electron-sharing (triplet-triplet) model, effectively characterizes the electronic structures in the CO trapping reaction involving four-membered-ring G13/G15-FLPs. Theoretical findings, derived from EDA-NOCV and frontier molecular orbital theory, demonstrate that the CO capture reaction by G13/G15-FLP involves two distinct bonding interactions. The first interaction is characterized by FLP-to-CO forward bonding, with the lone pair of G15 (G13/G15-FLP) donating to the empty p-π* orbital of carbon (CO), which predominates. The second interaction involves CO-to-FLP backward bonding, where the empty σ* orbital of G13 (G13/G15-FLP) accepts the lone pair of carbon (CO), albeit to a lesser extent. In summary, our theoretical findings indicate that the G13-C and G15-C bonds in the G15/G15-TS species with a four-membered ring can be classified as two dative single bonds. The importance of the interaction between Lewis bases and CO surpasses that of the interaction between Lewis acids and CO. Theoretical evidences in this study demonstrate a linear connection between the G13-G15 bond length within the four-membered-ring G13/G15-FLP and the activation barrier linked to CO capture. The activation strain model analysis in this study suggests that the activation energy required for bond formation primarily depends on the geometric deformation energy of G13/G15-FLP in capturing CO. Our DFT investigation shows that Hammond's postulate is obeyed by the CO catching reaction of the four-membered-ring G13/N-FLP, meaning that an earlier transition state is associated with a lower activation barrier, but not with the CO catching reaction of the four-membered-ring B/G15-FLP.

8.
Ann Acad Med Singap ; 53(2): 80-89, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38920232

RESUMEN

Introduction: We presented the key findings from Singapore's Changi General Hospital Breast Centre's lymphedema surveillance strategy that used patients' reported symptoms, standard arm circumference measurements and clinical assessment in the diagnosis of breast cancer-related lymphedema (BCRL). Our secondary aim was to highlight and discuss important elements of a surveillance strategy that can be implemented to track this outcome measure of breast cancer treatment for future research. Method: We conducted a cross-sectional study of 511 breast cancer patients to assess the prevalence of BCRL and its associated risk factors. We defined BCRL prevalence rates based on patients' self-reporting, objective arm circumference measure-ments and clinical diagnosis based on International Society of Lymphology (ISL) staging. Results: The median follow-up of patients was 88.8 months. The cumulative prevalence rate in the cohort was 30.9%. The cohort of BCRL patients were older (58.4 versus [vs] 54.9 years), had higher mean Body Mass Index (27.7 vs 25.2), higher proportion of mastectomy (77% vs 64.3%), axillary clearance, less likely breast reconstruction, higher-grade tumour, more lymph nodes excised, more advanced nodal disease, and had undergone adjuvant chemotherapy. However, clinically apparent BCRL was only 6.5% (33 out of 511 patients). The proportion of clinically significant BCRL in patients undergoing sentinel lymph node biopsy (SLNB) or axillary sampling was 1.7% compared to 9.9% in patients who had undergone axillary clearance. Majority of the BCRL were subclinical or mild in severity. Conclusion: Our study showed that our rates of BCRL were comparable to international rates and highlighted similar patient profiles who were at risk of developing the disease. Having a comprehensive lymphedema surveillance strategy is paramount in paving the way for future studies.


Asunto(s)
Linfedema del Cáncer de Mama , Humanos , Femenino , Persona de Mediana Edad , Prevalencia , Estudios Transversales , Factores de Riesgo , Singapur/epidemiología , Linfedema del Cáncer de Mama/epidemiología , Linfedema del Cáncer de Mama/diagnóstico , Linfedema del Cáncer de Mama/etiología , Mastectomía/efectos adversos , Anciano , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Brazo , Adulto , Índice de Masa Corporal , Escisión del Ganglio Linfático/efectos adversos , Estadificación de Neoplasias , Linfedema/epidemiología , Linfedema/etiología , Linfedema/diagnóstico , Autoinforme , Vigilancia de la Población/métodos
9.
Inorg Chem ; 63(24): 11219-11232, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38833519

RESUMEN

Computational exploration using the density functional theory framework (M06-2X-D3/def2-TZVP) was undertaken to investigate the [1 + 2] cycloaddition reaction between a five-membered-ring heterocyclic carbene analogue (G14-Rea; G14 = group 14 element) and a heavy acetylene molecule (G14G14-Rea). It was theoretically observed that exclusively Si-Rea, Ge-Rea, and Sn-Rea demonstrate the capacity to participate in the [1 + 2] cycloaddition reaction with the triply bonded SiSi-Rea. In addition, only three heavy acetylenes (SiSi-Rea, GeGe-Rea, and SnSn-Rea) can catalyze the [1 + 2] cycloaddition reaction with Si-Rea. Our theoretical findings elucidated that the reactivity trend observed in these [1 + 2] cycloaddition reactions primarily arise from the deformation energies of the distorted G14G14-Rea. Also, our study reveals that the bonding characteristics of their respective transition states are controlled by the singlet-singlet interaction (donor-acceptor interaction), rather than the triplet-triplet interaction (electron-sharing interaction). Additionally, our work demonstrates that the bonding behavior between G14-Rea and G14G14-Rea is predominantly determined by the filled p-π orbital of G14G14-Rea (HOMO) → the empty perpendicular p-π orbital of G14-Rea (LUMO), rather than the vacant p-π* orbital of G14G14-Rea (LUMO) ← the filled sp2 orbital of G14-Rea (HOMO).

10.
ACS Omega ; 9(23): 24396-24405, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38882171

RESUMEN

Aiming at the problem of transportation for heavy oil during the middle-later development stages of the Lvda oilfield, based on the self-developed design of a visual circulating flow experimental apparatus for heavy oil-water two-phase flow-the flow regime characteristics and corresponding drag properties of the two-phase flow of Lvda viscous oil, which is simulated by 500# industrial white oil and water in a horizontal pipeline are investigated experimentally. According to the Kelvin-Helmholtz instability theory, the flow pattern transition criteria from stratified flow to annular flow (AF) are proposed. The effects of 0.11-0.90 m/s oil superficial velocities, 0.06-1.49 m/s water superficial velocities, and 0.09-0.93 input water cuts on the drag reduction effect of different flow regimes are analyzed. The experimental results indicated that with the increase of mixing velocity and water volume fraction, stratified flow, AF, oil plug flow, and dispersed oil lump flow are successively observed in the horizontal heavy oil-water two-phase flow, in which AF is the main flow pattern. As the Froude number increases to 4.0, the input water volume fraction does not change any more and remains at about 10% of the total flow rate in the process of converting from stratified flow to AF. The four delivery approaches can archive the reduction of transportation resistance for heavy oil at different degrees, in which the transportation of heavy oil surrounded by a water ring has the best effect of drag reduction. At the optimal working conditions of 0.61 m/s oil superficial velocity, 0.07 m/s water superficial velocity, and 0.10 input water cut, the pressure drop of water annulus conveying for heavy oil is only 1/62.54 of that of separate transport for pure heavy oil under the same oil flow rate.

11.
Chembiochem ; : e202400254, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38757240

RESUMEN

In this work, a highly sensitive and selective method for detecting folic acid (FA) was developed using D-penicillamine (DPA) stabilized Ag/Cu alloy nanoclusters (DPA@Ag/Cu NCs). The yellow emission of DPA@Ag/Cu NCs was found to be quenched upon the addition of FA to the system. The fluorescence intensity quenching value demonstrated a linear relationship with FA concentrations ranging from 0.01 to 1200 µM, with a limit of detection (LOD) of 5.3 nM. Furthermore, the detection mechanism was investigated through various characterization analyses, including high resolution transmission electron microscopy, fluorescence spectra, ultraviolet-visible absorption spectra, and fluorescence lifetime. The results indicated that the fluorescence quenching induced by FA was a result of electron transfer from FA to the ligands of DPA@Ag/Cu NCs. The selectivity of the FA sensor was also evaluated, showing that common amino acids and inorganic ions had minimal impact on the detection of FA. Moreover, the standard addition method was successfully applied to detect FA in human serum, chewable tablets and FA tablets with promising results. The use of DPA@Ag/Cu NCs demonstrates significant potential for detecting FA in complex biological samples.

12.
Food Chem ; 454: 139796, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38797102

RESUMEN

This study aimed to present a selective and effective method for analyzing quinolones (QNs) in food matrix. Herein, a NiFe2O4-based magnetic sodium disulfonate covalent organic framework (NiFe2O4/COF) was prepared using a simple solvent-free grinding method, and was adopted as a selective adsorbent for magnetic solid phase extraction of QNs. Coupled with UHPLC-Q-Orbitrap HRMS, an efficient method for simultaneous detection of 18 kinds of QNs was established. The method exhibited good linearity (0.01-100 ng g-1), high sensitivity (LODs ranging from 0.0011 to 0.0652 ng g-1) and precision (RSDs below 9.5%). Successful extraction of QNs from liver and kidney samples was achieved with satisfactory recoveries ranging from 82.2% to 108.4%. The abundant sulfonate functional groups on NiFe2O4/COF facilitated strong affinity to QNs through electrostatic and hydrogen bonding interactions. The proposed method provides a new idea for the extraction of contaminants with target selectivity.


Asunto(s)
Compuestos Férricos , Contaminación de Alimentos , Estructuras Metalorgánicas , Quinolonas , Extracción en Fase Sólida , Extracción en Fase Sólida/métodos , Extracción en Fase Sólida/instrumentación , Quinolonas/análisis , Quinolonas/aislamiento & purificación , Quinolonas/química , Cromatografía Líquida de Alta Presión , Contaminación de Alimentos/análisis , Animales , Estructuras Metalorgánicas/química , Compuestos Férricos/química , Níquel/química , Níquel/análisis , Níquel/aislamiento & purificación , Espectrometría de Masas , Adsorción , Hígado/química
13.
Int J Surg ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38768466

RESUMEN

BACKGROUND: Robotic mastectomy has been performed worldwide since 2015. The advantages of the robotic approach in nipple-sparing mastectomy have been proven with better visualization and preservation of blood supply to the nipple-areolar complex (NAC), with a lower incidence of necrosis. It also allows smaller incisions for both mastectomy and immediate breast reconstruction. To date, no centers in Singapore and Southeast Asia offer robotic mastectomy. We believe that robotic mastectomy is a feasible and safe technique that can be utilized by our population. OBJECTIVES: This study aimed to ascertain the surgical outcomes and perform a learning curve analysis in patients undergoing robotic mastectomy in a multi-ethnic South East Asian population. METHODS: A single arm prospective pilot study of eligible patients aged 21-70 years old with early breast cancer or high-risk patients indicated for risk reducing mastectomy who were eligible and consented for robotic mastectomy were enrolled in this trial from 22nd December 2022 to 15th December 2023. RESULTS: A total of 29 consecutive robotic mastectomies were performed. The mean total operative time was 95±10.2 minutes. The average blood loss was 5.7±1.9 ml and the average length of stay was 1.05 days. The mean mastectomy specimen weight was 251 g, and there was no conversion to conventional mastectomy in any case. Furthermore, there were no 30-days morbidity or complications in terms of wound infection requiring intervention, flap and nipple-areolar complex (NAC) necrosis, and postoperative hematoma/bleeding requiring intervention. CONCLUSION: This study contributes to the current evidence that robotic mastectomy is a safe and feasible option, and could prove to be a great alternative to conventional mastectomy. Further prospective trials examining the long-term oncological outcomes of robotic mastectomy will be performed to establish the oncologic safety of this technique in breast cancer treatment.

14.
Nutrients ; 16(9)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38732573

RESUMEN

The role of selenium in the developmental process of esophageal cancer (EC) requires further investigation. To explore the relationship between selenium-related factors and EC through bioinformatic analysis, a case-control study was conducted to verify the results. Utilizing the GEPIA and TCGA databases, we delineated the differential expression of glutathione peroxidase 3 (GPx3) in EC and normal tissues, identified differentially expressed genes (DEGs), and a performed visualization analysis. Additionally, 100 pairs of dietary and plasma samples from esophageal precancerous lesions (EPLs) of esophageal squamous cancer (ESCC) cases and healthy controls from Huai'an district, Jiangsu, were screened. The levels of dietary selenium, plasma selenium, and related enzymes were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) or ELISA kits. The results showed lower GPx3 expression in tumor tissues compared to normal tissues. Further analysis revealed that DEGs were mainly involved in the fat digestion and absorption pathway, and the core protein fatty acid binding protein 1 (FABP1) was significantly upregulated and negatively correlated with GPx3 expression. Our case-control study found that selenium itself was not associated with EPLs risk. However, both the decreased concentration of GPx3 and the increase in FABP1 were positively correlated with the EPLs risk (p for trend = 0.035 and 0.046, respectively). The different expressions of GPx3 and FABP1 reflect the potential of selenium for preventing ESCC at the EPLs stage. GPx3 may affect myocardial infarction through FABP1, which remains to be further studied.


Asunto(s)
Biología Computacional , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Proteínas de Unión a Ácidos Grasos , Glutatión Peroxidasa , Selenio , Humanos , Selenio/sangre , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/sangre , Estudios de Casos y Controles , Neoplasias Esofágicas/prevención & control , Neoplasias Esofágicas/genética , Biología Computacional/métodos , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Carcinoma de Células Escamosas de Esófago/prevención & control , Carcinoma de Células Escamosas de Esófago/genética , Femenino , Masculino , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Anciano
15.
J Natl Compr Canc Netw ; 22(2D)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744306

RESUMEN

BACKGROUND: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. METHODS: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. RESULTS: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. CONCLUSIONS: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.


Asunto(s)
Adenocarcinoma Mucinoso , Neoplasias de la Mama , Receptor ErbB-2 , Receptores de Estrógenos , Humanos , Femenino , Receptor ErbB-2/metabolismo , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/metabolismo , Persona de Mediana Edad , Anciano , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidad , Pronóstico , Receptores de Estrógenos/metabolismo , Adulto , Receptores de Progesterona/metabolismo , Estadificación de Neoplasias , Carcinoma Ductal de Mama/terapia , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/metabolismo , Estudios de Cohortes , Carcinoma Lobular/terapia , Carcinoma Lobular/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/epidemiología
16.
J Am Chem Soc ; 146(21): 14410-14415, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38754079

RESUMEN

Strained cyclic tetrylones are important synthons due to various synthetic applications. Connecting two cyclic tetrylone rings through a single shared quaternary group 14 element atom to form a spirocyclic molecule has been unexplored both theoretically and experimentally. The formation of a spirocyclic motif has been a synthetic challenge. In contrast, the reaction of amidinato disilicon(I) 1, (Me3P)2SiCl4, and KC8 afforded π-delocalized spiro[3.3]heptasila-2,6-diylidone2 and tetrasilacyclobutadiene byproducts 3 and 4. Compound 2 is the smallest spirocyclic tetrylone derivative, which is composed of a σ-type lone pair and delocalized π bond in each all-silicon spirocyclic ring. The electronic property is supported by its coordination with a W(CO)5 moiety.

17.
Glob Med Genet ; 11(2): 142-149, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38606422

RESUMEN

Objectives This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. Methods This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted. Results We selected 91 patients diagnosed with acute leukemia and ICH. The overall 30-day mortality rate was 61.5%, with 56 of the 91 patients succumbing. Among those with LDH levels ≥ 570 U/L, the mortality rate was 74.4% (32 out of 43), which was higher than the 50% mortality rate of the LDH < 570 U/L group (24 out of 48) ( p = 0.017). In our multivariate regression models, the hazard ratios and their corresponding 95% confidence intervals for Log2 and twice the upper limit of normal LDH were 1.27 (1.01, 1.58) and 2.2 (1.05, 4.58), respectively. Interaction analysis revealed no significant interactive effect on the relationship between LDH levels and 30-day mortality. Conclusions Serum LDH level was associated with 30-day mortality, especially in patients with LDH ≥ 570 U/L.

18.
Nat Commun ; 15(1): 3052, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594261

RESUMEN

Derivatives of free monocoordinated borylenes have attracted considerable interest due to their ability to exhibit transition-metal-like reactivity, in particular small molecules capture. However, such complexes are rare as the formation is either endergonic, or the resulting adduct is a transient intermediate that is prone to reaction. Here, we present the synthesis of two bis(N-heterocyclic carbene)-borylene complexes capable of capturing and functionalizing carbon dioxide. The capture and subsequent functionalization of CO2 by the bis(NHC)-disilylamidoborylene 1 is demonstrated by the formation of the bis(NHC)-isocyanatoborylene-carbon dioxide complex 3. Reversible capture of CO2 is observed using the bis(NHC)-mesitylborylene 2, and the persistent bis(NHC)-mesitylborylene-carbon dioxide adduct 4 can be stabilized by hydrogen bonding with boric acid. The reactions of 4 with ammonia-borane and aniline demonstrate that the captured CO2 can be further functionalized.

19.
Inorg Chem ; 63(19): 8511-8515, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38687917

RESUMEN

A digermanium(III) 1,2-dication comprises two cationic centers located at two interconnected Ge atoms. The strong Coulombic repulsion between two positively charged germanium cations hinders their bond formation. Balancing these two oppositions was achieved by using amidinate and cyclic (alkyl)amino carbene (cAAC)-phosphinidenide ligands, where an amidinato cAAC-phosphinidenidogermylene complex, [LGeP(cAACMe)] (2, where L = PhC(NtBu)2, cAACMe = :C{C(Me)2CH2C(Me)2NAr}, and Ar = 2,6-iPr2C6H3), underwent one-electron oxidation with a bis(phosphinidene) radical cation, [(cAACMe)P]2•+, to form a digermanium(III) 1,2-dication, [LGeP(cAACMe)]22+, in compound 4.

20.
J Agric Food Chem ; 72(18): 10616-10626, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38656193

RESUMEN

Deoxynivalenol (DON) is a common food contaminant that can impair male reproductive function. This study investigated the effects and mechanisms of DON exposure on progenitor Leydig cell (PLC) development in prepubertal male rats. Rats were orally administrated DON (0-4 mg/kg) from postnatal days 21-28. DON increased PLC proliferation but inhibited PLC maturation and function, including reducing testosterone levels and downregulating biomarkers like HSD11B1 and INSL3 at ≥2 mg/kg. DON also stimulated mitochondrial fission via upregulating DRP1 and FIS1 protein levels and increased oxidative stress by reducing antioxidant capacity (including NRF2, SOD1, SOD2, and CAT) in PLCs in vivo. In vitro, DON (2-4 µM) inhibited PLC androgen biosynthesis, increased reactive oxygen species production and protein levels of DRP1, FIS1, MFF, and pAMPK, decreased mitochondrial membrane potential and MFN1 protein levels, and caused mitochondrial fragmentation. The mitochondrial fission inhibitor mdivi-1 attenuated DON-induced impairments in PLCs. DON inhibited PLC steroidogenesis, increased oxidative stress, perturbed mitochondrial homeostasis, and impaired maturation. In conclusion, DON disrupts PLC development in prepubertal rats by stimulating mitochondrial fission.


Asunto(s)
Células Intersticiales del Testículo , Mitocondrias , Dinámicas Mitocondriales , Estrés Oxidativo , Ratas Sprague-Dawley , Tricotecenos , Animales , Masculino , Dinámicas Mitocondriales/efectos de los fármacos , Ratas , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Células Intersticiales del Testículo/citología , Tricotecenos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Testosterona/metabolismo , Células Madre/efectos de los fármacos , Células Madre/metabolismo , Células Madre/citología , Humanos , Dinaminas/metabolismo , Dinaminas/genética , Potencial de la Membrana Mitocondrial/efectos de los fármacos
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