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1.
Front Oncol ; 14: 1296401, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962269

RESUMO

Introduction: Epithelioid hemangioma (EH) is an intermediate locally aggressive tumor that consists of epithelioid cells and endothelial cell differentiation, which can occur at any age, but is most common between the ages of 30 and 40 years. EH in the thoracic spine is rare, and accurate diagnosis is critical to treatment planning. Our aim was to explore the imaging and clinical data of thoracic spine EH to improve the understanding of this rare disease. Methods: From January 1, 2018 to June 30, 2023, a database of thoracic spine masses was retrospectively reviewed. Five patients with histologically proven thoracic spine EH and complete imaging available were identified and analyzed. Computed tomography (CT) and magnetic resonance imaging (MRI) findings were evaluated separately by two radiologists with more than 10 years of experience. Positron emission tomography (PET)/CT was conducted by two nuclear medicine diagnostic technologists with at least 5 years of experience. Results: The patients included three male and two female patients aged 23 to 56 years (mean age was 38.4 ± 14.3 years). All patients underwent CT, MRI, and 18F-FDG PET/CT examination before treatment. Four patients were limited to one vertebral involvement, only one patient had multiple vertebral involvement, and all tumors involved the accessories, including one involving the posterior ribs. The maximum diameter of the tumor ranged from 2.7 to 4.3. Conclusions: CT, MRI, and 18F-FDG PET/CT findings of thoracic spine EH have certain characteristics, and understanding these imaging findings will help to obtain accurate diagnosis before surgery.

2.
Nat Immunol ; 25(6): 969-980, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38831104

RESUMO

Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117L variant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.


Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico , Receptor 7 Toll-Like , Lúpus Eritematoso Sistêmico/genética , Humanos , Animais , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Camundongos , Criança , Feminino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Masculino , Idade de Início , Variação Genética , NF-kappa B/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Adolescente , Células THP-1 , Interferon Tipo I/metabolismo
3.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167290, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38866113

RESUMO

N6-methyladenosine (m6A) is the most abundant modification controlling RNA metabolism and cellular functions, but its roles in placental development are still poorly understood. Here, we characterized the synchronization of m6A modifications and placental functions by mapping the m6A methylome in human placentas (n = 3, each trimester), revealing that the dynamic patterns of m6A were associated with gene expression homeostasis and different biological pathways in placental development. Then, we generated trophoblast-specific knockout mice of Wtap, a critical component of methyltransferase complex, and demonstrated that Wtap was essential for trophoblast proliferation, placentation and perinatal growth. Further in vitro experiments which includes cell viability assays and series molecular binding assays demonstrated that WTAP-m6A-IGF2BP3 axis regulated the RNA stability and translation of Anillin (ANLN) and VEGFA, promoting trophoblast proliferation and secretion. Dysregulation of this regulatory axis was observed in placentas from pregnancies with fetal growth restriction (FGR) or preeclampsia, revealing the pathogenic effects of imbalanced m6A modifications. Therefore, our findings provide novel insights into the functions and regulatory mechanisms of m6A modifications in placental development and placental-related gestational diseases.

4.
Opt Express ; 32(10): 17667-17688, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858944

RESUMO

We propose a high-resolution, broad-spectral-range spatial heterodyne Raman spectrometer (SHRS) having separate filters and multi-gratings (SFMG). A prototype of the SFMG-SHRS is built using multi-gratings with four sub-gratings having groove densities of 320, 298, 276, and 254 gr/mm and separate filters with filter bands corresponding to the sub-gratings. We use the SFMG-SHRS to measure the Raman spectra of inorganic and organic compounds with various integration times, laser power, and transparent containers, compare measurements of microplastics with and without the separate filters, and measure mixtures of inorganic powders and organic solutions. The designed SFMG-SHRS makes high-resolution, broad-spectral-range Raman measurements with improved signal-to-noise ratios and visibility of weak Raman peaks even in the presence of fluorescence.

5.
Opt Express ; 32(10): 17819-17836, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858953

RESUMO

We propose a spatial heterodyne Raman spectrometer (SHRS) based on a field-widened grating-echelle (FWGE). A normal grating is combined with an echelle grating in a conventional spatial heterodyne spectrometer to eliminate ghost images without using masks, and prevents interference among the spatial frequencies of different diffraction orders. Mathematical expressions and derivation processes are given for the spectral parameters in the FWGE-SHRS and a verification breadboard system is fabricated. The FWGE-SHRS measures Raman spectra of single chemicals and mixed targets with different integration times, laser powers, concentrations, and transparent containers. The results of the experiments demonstrate that the FWGE-SHRS is suitable for high-resolution, broadband Raman measurements for a wide range of applications.

6.
Curr Med Imaging ; 20(1): e15734056259418, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38918998

RESUMO

BACKGROUND: Accurately predicting the hepatocellular carcinoma (HCC) grade may facilitate the rational selection of treatment strategies. The diagnostic efficacy of the combination of Gadolinium ethoxybenzy diethylenetriamine pentaacetic (Gd-EOB-DTPA) enhancement T1 mapping and apparent diffusion coefficient (ADC) values in predicting HCC grade needs further validation. OBJECTIVES: This study aimed to assess the capacity of Gd-EOB-DTPA-enhanced T1 mapping and ADC values, both individually and in combination, to discriminate between different grades of HCC. MATERIALS AND METHODS: From July 2017 to February 2020, 96 patients (male, 83; mean age, 53.67 years; age range, 29-71 years) clinically diagnosed with HCC were included in the present study. All patients underwent Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI, including T1 mapping sequence) before surgery or biopsy. All the patients were categorized into 3 groups according to the pathological results (including 24 cases of well-differentiated HCCs, 59 cases of moderately differentiated HCCs, 13 cases of and poorly differentiated HCCs). The mean Gd-EOB-DTPA enhanced T1 values (ΔT1=[(T1pre-T1post)/T1pre]×100%) and ADC values between different grading groups of HCC were calculated and compared. The area under the characteristics curve (AUC), the diagnostic threshold, sensitivity, and specificity of ΔT1 and ADC for differential diagnosis were analyzed. RESULTS: Mean ΔT1 was 58% for well-differentiated HCCs, 50% for moderately-differentiated HCCs, and 43% for poorly-differentiated HCCs. ΔT1 showed statistical differences between the groups (P<0.001). The mean ADC values of the 3 groups were 1.11×10-3 mm2/s, 0.91×10-3 mm2/s, and 0.80×10-3mm2/s, respectively. ADC showed statistical differences between the groups (P<0.001). In discriminating well- differentiated group from the moderately differentiated group, the AUC of ΔT1 was 0.751 (95% CI: 0.642, 0.859), the AUC of ADC was 0.782 (95% CI: 0.671, 0.894), the AUC of combined model was 0.811 (95% CI: 0.709, 0.914). In discriminating the poorly differentiated group from the moderately differentiated group, the AUC of ΔT1 was 0.768 (95% CI: 0.634, 0.902), the AUC of ADC was 0.754 (95% CI: 0.603, 0.904), and the AUC of the combined model was 0.841 (95% CI: 0.729, 0.953). CONCLUSION: Gd-EOB-DTPA enhanced T1 mapping, and ADC values have complementary effects on the sensitivity and specificity for identifying different HCC grades. A combined model of Gd-EOB-DTPA-enhanced MRI T1 mapping and ADC values could improve diagnostic performance for predicting HCC grades.

.


Assuntos
Carcinoma Hepatocelular , Meios de Contraste , Gadolínio DTPA , Neoplasias Hepáticas , Gradação de Tumores , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Adulto , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Curva ROC
7.
Eur J Radiol ; 176: 111514, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776804

RESUMO

PURPOSE: To assess the utility of apparent diffusion coefficients (ADCs) of whole tumor volume (WTV) and functional tumor volume (FTV) in determining the pathologicalprognostic factors in epithelial ovarian cancers (EOCs). METHODS: A total of 155 consecutive patients who were diagnosed with EOC between January 2017 and August 2022 and underwent both conventional magnetic resonance imaging and diffusion-weighted imaging were assessed in this study. The maximum, minimum, and mean ADC values of the whole tumor (ADCwmax, ADCwmin, and ADCwmean, respectively) and functional tumor (ADCfmax, ADCfmin, and ADCfmean, respectively) as well as the WTV and FTV were derived from the ADC maps. The univariate and multivariate logistic regression analyses and receiver operating characteristic curve (ROC) analysis were used to assess the correlation between these ADC values and the pathological prognostic factors, namely subtypes, lymph node metastasis (LNM), Ki-67 index, and p53 expression. RESULTS: The ADCfmean value was significantly lower in type II EOC, LNM-positive, and high-Ki-67 index groups compared to the type I EOC, LNM-negative, and low-Ki-67 index groups (p ≤ 0.001). Similarly, the ADCwmean and ADCfmean values were lower in the mutant-p53 group compared to the wild-type-p53 group (p ≤ 0.001). Additionally, the ADCfmean showed the highest area under the ROC curve (AUC) for evaluating type II EOC (0.725), LNM-positive (0.782), and high-Ki-67 index (0.688) samples among the given ROC curves, while both ADCwmean and ADCfmean showed high AUCs for assessing p53 expression (0.694 and 0.678, respectively). CONCLUSION: The FTV-derived ADC values, especially ADCfmean, can be used to assess preoperative prognostic factors in EOCs.


Assuntos
Carcinoma Epitelial do Ovário , Imagem de Difusão por Ressonância Magnética , Neoplasias Ovarianas , Carga Tumoral , Humanos , Feminino , Imagem de Difusão por Ressonância Magnética/métodos , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Carcinoma Epitelial do Ovário/patologia , Prognóstico , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Idoso , Adulto , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Metástase Linfática/diagnóstico por imagem
8.
Front Cell Infect Microbiol ; 14: 1382145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736748

RESUMO

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a new threat in recent years, owing to its rapidly increasing resistance to antibiotics and new effective therapies are needed to combat this pathogen. Phage therapy is considered to be the most promising alternative for treating CRAB infections. In this study, a novel phage, Ab_WF01, which can lyse clinical CRAB, was isolated and characterized from hospital sewage. The multiplicity of infection, morphology, one-step growth curve, stability, sensitivity, and lytic activity of the phage were also investigated. The genome of phage Ab_WF01 was 41, 317 bp in size with a GC content of 39.12% and encoded 51 open reading frames (ORFs). tRNA, virulence, and antibiotic resistance genes were not detected in the phage genome. Comparative genomic and phylogenetic analyses suggest that phage Ab_WF01 is a novel species of the genus Friunavirus, subfamily Beijerinckvirinae, and family Autographiviridae. The in vivo results showed that phage Ab_WF01 significantly increased the survival rate of CRAB-infected Galleria mellonella (from 0% to 70% at 48 h) and mice (from 0% to 60% for 7 days). Moreover, after day 3 post-infection, phage Ab_WF01 reduced inflammatory response, with strongly ameliorated histological damage and bacterial clearance in infected tissue organs (lungs, liver, and spleen) in mouse CRAB infection model. Taken together, these results show that phage Ab_WF01 holds great promise as a potential alternative agent with excellent stability for against CRAB infections.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Carbapenêmicos , Genoma Viral , Terapia por Fagos , Filogenia , Esgotos , Acinetobacter baumannii/virologia , Acinetobacter baumannii/efeitos dos fármacos , Esgotos/virologia , Esgotos/microbiologia , Animais , Carbapenêmicos/farmacologia , Bacteriófagos/genética , Bacteriófagos/fisiologia , Bacteriófagos/classificação , Bacteriófagos/isolamento & purificação , Infecções por Acinetobacter/microbiologia , Camundongos , Antibacterianos/farmacologia , Fases de Leitura Aberta , Modelos Animais de Doenças , Mariposas/virologia , Mariposas/microbiologia , Composição de Bases
9.
ACS Appl Mater Interfaces ; 16(21): 27419-27428, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38743926

RESUMO

Phenolic resin (PF) is considered a promising precursor of hard carbon (HC) for advanced-performance anodes in sodium-ion batteries (SIBs) because of its facile designability and high residual carbon yield. However, understanding how the structure of PF precursors influences sodium storage in their derived HC remains a significant challenge. Herein, the microstructure of HC is controlled by the degree of cross-linking of resorcinol-benzaldehyde (RB) resin. We reveal that robust molecular cross-linking in RB resin induced by hydrothermal treatment promotes closed-pore formation in the derived HC. The mechanism is devised for the decomposition of a highly cross-linked RB three-dimensional network into randomly stacked short-range graphitic microcrystals during high-temperature carbonization, contributing to the abundant closed pores in the derived HC. In addition, the high cross-linking degree of RB resin endows its derived HC with a small-sized spherical morphology and large interlayer spacing, which improves the rate performance of HC. Consequently, the optimized hydrothermal treatment HC anode shows a higher specific capacity of 372.7 mAh g-1 and better rate performance than the HC anode without hydrothermal treatment (276.0 mAh g-1). This strategy can provide feasible molecular cross-linking engineering for the development of closed pores in PF-based HC toward enhanced sodium storage.

10.
J Hypertens ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38780189

RESUMO

BACKGROUND: Unhealthy sleep patterns are common during pregnancy and have been associated with an increased risk of developing hypertensive disorders of pregnancy (HDPs) in observational studies. However, the causality underlying these associations remains uncertain. This study aimed to evaluate the potential causal association between seven sleep traits and the risk of HDPs using a two-sample Mendelian randomization study. METHODS: Genome-wide association study (GWAS) summary statistics were obtained from the FinnGen consortium, UK Biobank, and other prominent consortia, with a focus on individuals of European ancestry. The primary analysis utilized an inverse-variance-weighted MR approach supplemented by sensitivity analyses to mitigate potential biases introduced by pleiotropy. Furthermore, a two-step MR framework was employed for mediation analyses. RESULTS: The data analyzed included 200 000-500 000 individuals for each sleep trait, along with approximately 15 000 cases of HDPs. Genetically predicted excessive daytime sleepiness (EDS) exhibited a significant association with an increased risk of HDPs [odds ratio (OR) 2.96, 95% confidence interval (95% CI) 1.40-6.26], and the specific subtype of preeclampsia/eclampsia (OR 2.97, 95% CI 1.06-8.3). Similarly, genetically predicted obstructive sleep apnea (OSA) was associated with a higher risk of HDPs (OR 1.27, 95% CI 1.09-1.47). Sensitivity analysis validated the robustness of these associations. Mediation analysis showed that BMI mediated approximately 25% of the association between EDS and HDPs, while mediating up to approximately 60% of the association between OSA and the outcomes. No statistically significant associations were observed between other genetically predicted sleep traits, such as chronotype, daytime napping, sleep duration, insomnia, snoring, and the risk of HDPs. CONCLUSION: Our findings suggest a causal association between two sleep disorders, EDS and OSA, and the risk of HDPs, with BMI acting as a crucial mediator. EDS and OSA demonstrate promise as potentially preventable risk factors for HDPs, and targeting BMI may represent an alternative treatment strategy to mitigate the adverse impact of sleep disorders.

11.
Front Med (Lausanne) ; 11: 1408967, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818401

RESUMO

Primary clear cell carcinoma of liver (PCCCL) is a special and relatively rare subtype of hepatocellular carcinoma (HCC), which is more common in people over 50 years of age, with a preference for men and a history of hepatitis B or C and/or cirrhosis. Herein, we present a case of a 60-year-old woman who came to our hospital for medical help with right upper abdominal pain. The imaging examination showed a low-density mass in the right lobe of his liver. In contrast enhanced computed tomography (CT) or T1-weighted imaging, significant enhancement can appear around the tumor during the arterial phase, and over time, the degree of enhancement of the tumor gradually decreases. The lession showed obviously increased fluorine-18 fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography/CT. These imaging findings contribute to the diagnosis of PCCCL and differentiate it from other types of liver tumors.

12.
Front Med (Lausanne) ; 11: 1346647, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576707

RESUMO

Schwannomatosis is a rare autosomal dominant hereditary syndrome disease characterized by multiple schwannomas throughout the body, without bilateral vestibular schwannoma or dermal schwannoma. The most common location of schwannomatosis is the head and neck, as well as the limbs, while multiple schwannomas in the lumbosacral canal and lower extremities are relatively rare. In this study, we report a 79-year-old woman diagnosed with schwannomatosis. MRI and contrast-enhanced imaging revealed multiple schwannomas in both lower extremities. An 18F-FDG PET/CT examination revealed that in addition to multiple tumors with increased 18F-FDG uptake in both lower extremities, there was also an increased 18F-FDG uptake in a mass in the lumbosacral canal. These masses were confirmed to be schwannomas by pathology after surgery or biopsy. 18F-FDG PET/CT findings of schwannomas were correlated with MRI and pathological components. Antoni A area rich in tumor cells showed significant enhancement on contrast-enhanced T1WI, and PET/CT showed increased uptake of 18F-FDG in the corresponding area, while Antoni B region rich in mucus showed low enhancement on contrast-enhanced T1WI, accompanied by a mildly increased 18F-FDG uptake.

13.
Int Immunopharmacol ; 133: 112131, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38669945

RESUMO

BACKGROUND: Osthole is a natural active ingredient extracted from the traditional Chinese medicine Cnidium monnieri. It has been demonstrated to have anti-inflammatory, anti-fibrotic, and anti-hyperglycemic properties. However, its effect on diabetic kidney disease (DKD) remains uncertain. This study aims to assess the preventive and therapeutic effects of osthole on DKD and investigate its underlying mechanisms. METHODS: A streptozotocin/high-fat and high-sucrose diet induced Type 2 diabetic rat model was established. Metformin served as the positive drug control. Diabetic rats were treated with metformin or three different doses of osthole for 8 weeks. Throughout the treatment period, the progression of DKD was assessed by monitoring increases in urinary protein, serum creatinine, urea nitrogen, and uric acid, along with scrutinizing kidney pathology. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors and oxidative stress levels. At the same time, immunohistochemical staining was utilized to evaluate changes in alpha-smooth muscle actin, fibronectin, E-cadherin, and apoptosis. The alterations in TGF-ß1/Smads signaling pathway were ascertained through western blot and immunofluorescence. Furthermore, we constructed a high glucose-stimulated HBZY-1 cells model to uncover its molecular protective mechanism. RESULTS: Osthole significantly reduced fasting blood glucose, insulin resistance, serum creatinine, uric acid, blood urea nitrogen, urinary protein excretion, and glomerular mesangial matrix deposition in diabetic rats. Additionally, significant improvements were observed in inflammation, oxidative stress, apoptosis, and fibrosis levels. The increase of ROS, apoptosis and hypertrophy in HBZY-1 cells induced by high glucose was reduced by osthole. Immunofluorescence and western blot results demonstrated that osthole down-regulated the TGF-ß1/Smads signaling pathway and related protein expression. CONCLUSION: Our findings indicate that osthole exhibits potential preventive and therapeutic effects on DKD. It deserves further investigation as a promising drug for preventing and treating DKD.


Assuntos
Cumarínicos , Diabetes Mellitus Experimental , Nefropatias Diabéticas , Estresse Oxidativo , Transdução de Sinais , Animais , Humanos , Masculino , Ratos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Linhagem Celular , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Inflamação/tratamento farmacológico , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
14.
BMJ Open ; 14(4): e074493, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631826

RESUMO

INTRODUCTION: Pre-eclampsia (PE) affects about 5% of Chinese pregnant women and is a major cause of maternal and perinatal morbidity and mortality. The first trimester screening model developed by the Fetal Medicine Foundation, which uses the Bayes theorem to combine maternal characteristics and medical history together with measurements of biomarkers, has been proven to be effective and has superior screening performance to that of the traditional risk factor-based approach for the prediction of PE. Prophylactic use of low-dose aspirin in women at risk for PE has resulted in a lower incidence of preterm-PE. However, there is no consensus on the preferred aspirin dosage for the prevention of preterm-PE. Evidence has also suggested that metformin has the potential benefit in preventing PE in pregnant women who are at high risk of the disorder. METHOD AND ANALYSIS: We present a protocol (V.2.0, date 17 March 2022) for the AVERT trial, which is a multicentre, double-blinded, 3-arm randomised controlled trial (RCT) that uses an effective PE screening programme to explore the optimal dosage of aspirin and the role of metformin for the prevention of PE among high-risk pregnant women in China. We intend to recruit 66 000 singleton pregnancies without treatment of low-dose aspirin and metformin at 11-13 weeks' gestation and all eligible women attending for their first trimester routine scan will be invited to undergo screening for preterm-PE by the combination of maternal factors, mean arterial pressure and placental growth factor. Women found to be at high risk of developing preterm-PE will be invited to take part in the RCT. This study will compare the incidence of preterm-PE with delivery at <37 weeks' gestation, as the primary outcome, of three different interventional groups: (1) aspirin 75 mg daily, (2) aspirin 150 mg daily and (3) aspirin 75 mg with metformin 1.5 g daily. 957 participants per treatment group are required to detect a significant difference of 59% in the reduction of the incidence of preterm-PE with 80% power and type I error of 5%. Pregnancy and neonatal outcomes will be collected and analysed. ETHICS AND DISSEMINATION: Ethical approval for the study was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No. 2021.406) in Hong Kong and the Ethics Committee of each participating hospital in Mainland China. The study is registered at ClinicalTrials.gov. The results of the AVERT trial will be disseminated at international academic conferences and published in high-impact factor journals. TRIAL REGISTRATION NUMBER: NCT05580523.


Assuntos
Metformina , Pré-Eclâmpsia , Gravidez , Feminino , Recém-Nascido , Humanos , Aspirina , Pré-Eclâmpsia/epidemiologia , Método Duplo-Cego , China , Biomarcadores , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
15.
Soc Sci Med ; 348: 116785, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569281

RESUMO

Identifying environmental determinants of health and clarifying their variations is crucial for health promotion in different cities by providing tailored intervention strategies. Although the association between perceived urban environment and health (e.g., self-rated health) has been repeatedly explored, most studies have focused on cities of a specific size, and it is still unknown whether either significant environment variables or the magnitude of the association would vary across different-sized cities. This study investigated how perceived urban environment variables significantly associated with individuals' self-rated health varied from small cities to mega cities in China, based on a national survey including 5963 valid respondents. The results showed that the relationship between self-rated health and city size was U-shaped, with respondents in medium and large cities reporting a low-level self-rated health. Perceived greenness, public facilities, housing supply, and medical services were positively and significantly associated with self-rated health, with the odds ratio (OR) of 1.37 (95%CI: 1.29-1.46), 1.27 (95%CI: 1.19-1.35), 1.14 (95%CI: 1.09-1.20), and 1.17 (95%CI: 1.10-1.24), respectively. Furthermore, the magnitude of the association was significantly larger in mega cities. These findings provide useful evidence for promoting public health in cities of different sizes for achieving health equity and indicate that smaller cities and their health-supportive environment need further attention.


Assuntos
Cidades , Humanos , China , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Adulto , Autorrelato , Percepção , Nível de Saúde , Idoso , Inquéritos e Questionários , Adolescente
16.
Br J Radiol ; 97(1158): 1139-1145, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38662891

RESUMO

OBJECTIVE: This study aimed to explore the value of apparent diffusion coefficient (ADC) histogram based on whole lesion volume in distinguishing stage IA endometrial carcinoma from the endometrial polyp. METHODS: MRI of 108 patients with endometrial lesions confirmed by pathology were retrospectively analysed, including 65 cases of stage IA endometrial carcinoma and 43 cases of endometrial polyp. The volumetric ADC histogram metrics and general imaging features were evaluated and measured simultaneously. All the features were compared between the 2 groups. The receiver operating characteristic curve was utilized to evaluate the diagnostic performance. RESULTS: The mean, max, min, and percentiles (10th, 25th, 50th, 75th, 95th) ADC values of endometrial carcinoma were significantly lower than that of polyp (all P < .05). The skewness and kurtosis of ADC values in the endometrial carcinoma group were significantly higher than those in the endometrial polyp group, and the variance of ADC values in the endometrial carcinoma group was lower than those in the endometrial polyp group (all P < .05). Endometrial carcinoma demonstrated more obvious myometrial invasion combined with intralesion haemorrhage than polyp (all P < .05). The 25th percentile of ADC values achieved the largest areas under the curve (0.861) among all the ADC histogram metrics and general imaging features, and the sensitivity and specificity were 83.08% and 76.74%, with the cut-off value of 1.01 × 10-3 mm2/s. CONCLUSION: The volumetric ADC histogram analysis was an effective method in differentiating endometrial carcinoma from an endometrial polyp. The 25th percentile of ADC values has satisfactory performance for detecting malignancy in the endometrium. ADVANCES IN KNOWLEDGE: The ADC histogram metric based on whole lesion is a promising imaging-maker in differentiating endometrial benign and malignant lesions.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias do Endométrio , Pólipos , Humanos , Feminino , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Pólipos/diagnóstico por imagem , Pólipos/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Idoso , Adulto , Sensibilidade e Especificidade , Estadiamento de Neoplasias , Endométrio/diagnóstico por imagem , Endométrio/patologia , Curva ROC
17.
Nat Sci Sleep ; 16: 369-379, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638411

RESUMO

Purpose: While there is a rising focus on sleep issues among athletes, a notable gap exists in the comparative analysis of sleep patterns between male and female athletes. This study aims to evaluate the sleep patterns of collegiate swimmers during a specific period (pre-competition training phase) based on the National Sleep Foundation's recommendations and compares sleep differences between males and females. Patients and Methods: 15 swimmers (6 males and 9 females) completed the Athlete Sleep Screening Questionnaire (ASSQ) and wore actigraphy devices for 8 consecutive nights to record objective sleep patterns including bedtime, wake time, sleep onset latency, total sleep time, wake after sleep onset, and sleep efficiency. Results: The total sleep time of collegiate male (5.0±0.4 h, 4.6 to 5.4h) and female (6.0±0.7 h, 5.5 to 6.5h) swimmers was less than 7 hours per night, and male swimmers' sleep efficiency (76.7±8.9%, 67.4 to 86.0%) was lower than the 85% standard. Male swimmers had less objectively measured sleep duration (p=0.006, d=1.66, large effect), lower sleep efficiency (p=0.013, d=1.51, large effect), and longer wake after sleep onset (p=0.096, d=0.94, moderate effect). Female swimmers had higher sleep difficulty scores (p=0.06, d=1.08, moderate effect), and there was a significant difference in the distribution of sleep difficulty scores between male and female swimmers (p=0.033, V=0.045, small effect). Conclusion: Collegiate swimmers exhibited poor sleep patterns during pre-competition preparation, and the sleep fragmentation of male swimmers was more pronounced. There were sex differences in both subjective and objective measured sleep patterns, with male swimmers having less sleep and low efficiency, while female swimmers experienced more significant sleep disturbances.

18.
Ecotoxicol Environ Saf ; 276: 116300, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583312

RESUMO

Bisphenol AF (BPAF), an analogue of bisphenol A (BPA), is commonly found in manufacturing industries and known for its endocrine-disrupting properties. Despite potential similarities in adverse effects with BPA, limited toxicological data exist specifically for BPAF and its impact on male reproductive physiology. This mini-review aims to elucidate the influence of BPAF on the male reproductive system, focusing on estrogenic effects, effects on the hypothalamus-pituitary-gonad (HPG) axis, steroidogenesis, spermatogenesis, and transgenerational reproductive toxicity. Additionally, we outline the current insights into the potential mechanisms underlying BPAF-induced male reproductive disorders. BPAF exposure, either directly or maternally, has been associated with detrimental effects on male reproductive functions, including damage to the blood-testis barrier (BTB) structure, disruptions in steroidogenesis, testis dysfunction, decreased anogenital distance (AGD), and defects in sperm and semen quality. Mechanistically, altered gene expression in the HPG axis, deficits in the steroidogenesis pathway, activation of the aromatase pathway, cascade effects induced by reactive oxygen species (ROS), activation of ERK signaling, and immunological responses collectively contribute to the adverse effects of BPAF on the male reproductive system. Given the high prevalence of male reproductive issues and infertility, along with the widespread environmental distribution of bisphenols, this study provides valuable insights into the negative effects of BPAF. The findings underscore the importance of considering the safe use of this compound, urging further exploration and regulatory attention to decrease potential risks associated with BPAF exposure.


Assuntos
Compostos Benzidrílicos , Disruptores Endócrinos , Fluorocarbonos , Fenóis , Masculino , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidade , Humanos , Animais , Saúde Reprodutiva , Reprodução/efeitos dos fármacos , Genitália Masculina/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Testículo/efeitos dos fármacos
19.
Clin Transl Med ; 14(3): e1627, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38515274

RESUMO

PURPOSE: Our preclinical studies showed that lycopene enhanced the anti-prostate cancer efficacy of docetaxel in animal models. A phase I trial (NCT0149519) was conducted to identify an optimum dose of synthetic lycopene in combination with docetaxel (and androgen blockade [androgen deprivation therapy, ADT]), and to evaluate its effect on the safety and pharmacokinetics of docetaxel in men with metastatic prostate cancer. METHODS: Subjects were treated with 21-day cycles of 75 mg/m2 docetaxel (and ADT), plus lycopene at 30, 90 or 150 mg/day. A Bayesian model averaging continual reassessment method was used to guide dose escalation. Pharmacokinetics of docetaxel and multiple correlative studies were carried out. RESULTS: Twenty-four participants were enrolled, 18 in a dose escalation cohort to define the maximum tolerated dose (MTD), and six in a pharmacokinetic cohort. Docetaxel/ADT plus 150 mg/day synthetic lycopene resulted in dose-limiting toxicity (pulmonary embolus) in one out of 12 participants with an estimated probability of .106 and thus was chosen as the MTD. Lycopene increased the AUCinf and Cmax of plasma docetaxel by 9.5% and 15.1%, respectively. Correlative studies showed dose-related changes in circulating endothelial cells and vascular endothelial growth factor A, and reduction in insulin-like growth factor 1R phosphorylation, associated with lycopene therapy. CONCLUSIONS: The combination of docetaxel/ADT and synthetic lycopene has low toxicity and favourable pharmacokinetics. The effects of lycopene on biomarkers provide additional support for the toxicity-dependent MTD definition. HIGHLIGHTS: The maximum tolerated dose was identified as 150 mg/day of lycopene in combination with docetaxel/ADT for the treatment of metastatic prostate cancer patients. Small increases in plasma exposure to docetaxel were observed with lycopene co-administration. Mechanistically significant effects were seen on angiogenesis and insulin-like growth factor 1 signalling by lycopene co-administration with docetaxel/ADT.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Docetaxel , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Licopeno/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Teorema de Bayes , Células Endoteliais/patologia
20.
Front Cell Infect Microbiol ; 14: 1360880, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529472

RESUMO

Metal ions are essential trace elements for all living organisms and play critical catalytic, structural, and allosteric roles in many enzymes and transcription factors. Mycobacterium tuberculosis (MTB), as an intracellular pathogen, is usually found in host macrophages, where the bacterium can survive and replicate. One of the reasons why Tuberculosis (TB) is so difficult to eradicate is the continuous adaptation of its pathogen. It is capable of adapting to a wide range of harsh environmental stresses, including metal ion toxicity in the host macrophages. Altering the concentration of metal ions is the common host strategy to limit MTB replication and persistence. This review mainly focuses on transcriptional regulatory proteins in MTB that are involved in the regulation of metal ions such as iron, copper and zinc. The aim is to offer novel insights and strategies for screening targets for TB treatment, as well as for the development and design of new therapeutic interventions.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Tuberculose/microbiologia , Metais/metabolismo , Homeostase/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Íons/metabolismo
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