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Objective: In order to explore the relationship between mammographic density of breast mass and its surrounding area and benign or malignant breast, this paper proposes a deep learning model based on C2FTrans to diagnose the breast mass using mammographic density. Methods: This retrospective study included patients who underwent mammographic and pathological examination. Two physicians manually depicted the lesion edges and used a computer to automatically extend and segment the peripheral areas of the lesion (0, 1, 3, and 5 mm, including the lesion). We then obtained the mammary glands' density and the different regions of interest (ROI). A diagnostic model for breast mass lesions based on C2FTrans was constructed based on a 7: 3 ratio between the training and testing sets. Finally, receiver operating characteristic (ROC) curves were plotted. Model performance was assessed using the area under the ROC curve (AUC) with 95% confidence intervals (CI), sensitivity, and specificity. Results: In total, 401 lesions (158 benign and 243 malignant) were included in this study. The probability of breast cancer in women was positively correlated with age and mass density and negatively correlated with breast gland classification. The largest correlation was observed for age (r = 0.47). Among all models, the single mass ROI model had the highest specificity (91.8%) with an AUC = 0.823 and the perifocal 5mm ROI model had the highest sensitivity (86.9%) with an AUC = 0.855. In addition, by combining the cephalocaudal and mediolateral oblique views of the perifocal 5 mm ROI model, we obtained the highest AUC (AUC = 0.877 P < 0.001). Conclusions: Deep learning model of mammographic density can better distinguish benign and malignant mass-type lesions in digital mammography images and may become an auxiliary diagnostic tool for radiologists in the future. [ABSTRACT FROM AUTHOR]

Background: Early detection, diagnosis, and treatment of children with CHD has been the focus of research attention. Hainan is the southernmost underdeveloped province in China, where the technology of screening, diagnosis, and treatment for children with CHD has not been fully developed. Objectives: This study aimed to introduce and promote an appropriate technology system for screening, diagnosis, and evaluation of neonatal CHD. Methods: Two indicators, namely cardiac auscultation plus pulse oximetry (POX), were used by screening staff to screen live newborns within six to 72 hours afterbirth at all screening institutions in Hainan province from January 1, 2019, to December 31,2021. Diagnosis procedure for the screened-positive newborns was performed in 31 certified medical institutions, and evaluation procedure for the newborns confirmed with CHD was performed in six certified medical institutions. Data about screening, diagnosis, evaluation, and treatment were obtained, uploaded, and managed online through a neonatal CHD screening information management net. Results: A total of 321447 live births were included in the CHD screening project, and an overall screening rate of 97.59% (321447/329387) was determined. According to our results, 8032 cases were screened-positive. A total of 1099 cases of CHD were confirmed, suggesting a CHD prevalence of 3.419 per 1000 live births. Atrial septal defect (ASD) was the most common CHD lesion, with a prevalence of 1.313 per 1000 live births. The sensitivity of cardiac auscultation, POX, and two indicators' combination (i.e., cardiac auscultation plus POX) for CHD detection were 69.15%, 33.49%, and 91.90%, respectively; and the specificity of them were 98.36%, 99.43%, and 97.81%, respectively. The ratio of both positive in two indicators among the children with major (serious and critical) CHD at the initial screening was significantly higher than that of single positive in any indicator (χ² = 59.455, P < 0.001). All children with CHD were evaluated, out of who 154 children with major CHD were treated promptly. Only 15 cases of children with major CHD died, and the standardized mortality of children aged 0-1 years with CHD was 4.67/100,000. Conclusions: It was concluded that the combination of two indicators (i.e., cardiac auscultation plus POX) for CHD screening was reliable as well as non-invasive, simple, and easy to operate so that it was conducive for promotion. It was also found that introducing and promoting an appropriate technology for screening, diagnosis, and evaluation of neonatal CHD were extremely significant since they may have contributed to the timely diagnosing and treating children with CHD, especially those with major CHD. [ABSTRACT FROM AUTHOR]

Despite the apparent clinical benefits of high-dose cytarabine (Ara-C) over lower dose Ara-C in acute myeloid leukemia (AML) therapy, the mechanism behind high-dose Ara-C therapy remains uncertain. In this study, a LC-MS-based method was carried out to investigate the metabolic alteration of ribonucleotide and deoxyribonucleotide in human promyelocytic leukemia cells (HL-60) after treatment with Ara-C to reveal its antitumor mechanism. The metabolic results revealed that four nucleotides (ATP, ADP, CDP, and dCTP) could be used as potential biomarkers indicating the benefit of high-dose Ara-C over lower dose Ara-C treatment. Combining metabolic perturbation and cell cycle analysis, we conjectured that, apart from the acknowledged mechanism of Ara-C on tumor inhibition, high-dose Ara-C could present a specific action pathway. It was suggested that the pronounced rise in AMP/ATP ratio induced by high-dose Ara-C can trigger AMP-activated protein kinase (AMPK) and subsequently Forkhead Box, class O (FoxO), to promote cell cycle arrest. Moreover, the significant decrease in CDP pool induced by high-dose Ara-C might further accelerate the reduction of dCTP, which then aggravates DNA synthesis disturbance. As a result, all of these alterations led to heightened tumor inhibition. This study provides new insight in the investigation of potential mechanisms in the clinical benefits of high-dose Ara-C in therapy for AML. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide reductase (RR) proteins were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) method, flow cytometry andWestern blot analysis, respectively. Our standardized PHA extract showed toxicity to HepG2 cells at high concentrations after 72 h exposure and induced G2/M cell cycle arrest. Combined use of 5-FU with PHA resulted in significant decreases in ATP, CTP, GTP, UTP and dTTP levels, while AMP, CMP, GMP and dUMP levels increased significantly compared with use of 5-FU alone. Further, PHA could increase the role of cell cycle arrest at S phase induced by 5-FU. Although PHA alone had no direct impact on TS and RR, PHA could change the levels of RNs and dRNs when combined with 5-FU. This may be due to cell cycle arrest or regulation of key enzyme steps in intracellular RNs and dRNs metabolism. [ABSTRACT FROM AUTHOR]

Background: Published studies have yielded inconsistent results on the relationship between p53 status and the progression of stage T1 non-muscle invasive bladder cancer (NMIBC). Therefore, we performed a meta-analysis to evaluate the prognostic value of p53 in T1 NMIBC. Methods: We systematically searched for relevant literatures in MEDLINE, EMBASE, and Web of Science. Data were pooled together from individual studies, and meta-analysis was performed. Study quality was assessed using the Newcastle-Ottawa Scale. Pooled risk ratios (RRs) and 95 % CI were calculated to estimate the effect sizes. Moreover, subgroup analyses were carried out. Results: A total of 12 studies comprising 712 patients were subjected to the final analysis. p53 overexpression was significantly associated with higher progression rate of T1 NMIBC (RR 2.32, 95 % CI 1.59-3.38). Moderate heterogeneity was observed across the studies (I2 = 39 %, P < 0.0001). In a subgroup analysis stratified by stage, p53 overexpression was a predictor of progression in T1 grade 3 NMIBC (RR 2.71, 95 % CI 1.31-5.64). In addition, in a subgroup analysis stratified by intravesical therapy, p53 overexpression was a predictor of progression in T1 NMIBC received Bacillus Calmette-Guérin intravesical therapy (RR 3.35, 95 % CI 1.89-5.93). Furthermore, after excluding the study that possibly contributed to the heterogeneity by the sensitivity analysis, the association p53 overexpression was significantly correlated with progression of T1 NMIBC (RR 2.74, 95 % CI 2.05-3.65) without evidence of heterogeneity (I2 = 0 %, P < 0.0001). Conclusions: This meta-analysis suggested that p53 overexpression may be associated with progression of T1 NMIBC patients. Because of the heterogeneity and other limitations, further studies with rigid criteria and large populations are still warranted to confirm our findings. [ABSTRACT FROM AUTHOR]

PerforalactoneA (1), a new 20S quassinoid with a unique cagelike 2,4-dioxaadamantane ring system and a migrated side chain, was isolated from the plant Harrisonia perforata together with two biosynthetically related new quassinoids. The structures of these natural products were elucidated by NMR spectroscopy, X-ray diffraction analysis, computational modeling, and the CD excitation chirality method. The compounds exhibited notable biological properties, including insecticidal activity against Aphis medicaginis Koch and antagonist activity at the nicotinic acetylcholine receptor of Drosophila melanogaster. The structural features of these compounds may be related to their promising biological characteristics. Their biosynthesis and an alternative origin of quassinoid-type natural products are also discussed. [ABSTRACT FROM AUTHOR]

Perforalactone A (1), a new 20S quassinoid with a unique cagelike 2,4-dioxaadamantane ring system and a migrated side chain, was isolated from the plant Harrisonia perforata together with two biosynthetically related new quassinoids. The structures of these natural products were elucidated by NMR spectroscopy, X-ray diffraction analysis, computational modeling, and the CD excitation chirality method. The compounds exhibited notable biological properties, including insecticidal activity against Aphis medicaginis Koch and antagonist activity at the nicotinic acetylcholine receptor of Drosophila melanogaster. The structural features of these compounds may be related to their promising biological characteristics. Their biosynthesis and an alternative origin of quassinoid-type natural products are also discussed. [ABSTRACT FROM AUTHOR]

Crohn's Disease (CD) is a chronic immune-mediated disorder with progressive and destructive course. Current guidelines on the treatment strategy still recommend a step-up approach with sequential prescription of corticosteroids and immunosuppressives. However, mounting evidences manifested that top-down therapy with early administration of anti-TNF or combination of immunosuppressives can achieve more rapid and higher rate of mucosal healing and has the potential of modifying the natural course of disease. Therefore, who is suitable to accept and when to start anti-TNF therapy have attracted the attention of gastroenterologists. And what benefit/risk can be expected from the two strategies should be carefully taken into account by clinicians. Age stratification, special patients, disease location and extension, genetic and serologic testing are predictors of disease progression and complication and thus guide a personalized treatment approach in CD. A definition of early CD has been proposed to select an algorithm for treatment of moderate-to-severe CD with a suitable strategy. To date mucosal healing has been widely used, the Lémann score, which assesses the extent and severity of bowel damage at a specific time-point and over time, and is a new disability index for patients with CD, will be considered as a new endpoint for future studies of treatment strategies. Besides medicines of the two strategies, surgery, vaccine, Leukocytapheresis and stem cell therapy are all effective therapeutic approaches which lead to another thinking about what should they be putted in the conditional pyramid. However, we are trying to answer these questions. [ABSTRACT FROM AUTHOR]