Carbonized Platycladus orientalis Derived Carbon Dots Accelerate Hemostasis through Activation of Platelets and Coagulation Pathways.

Achieving rapid and effective hemostasis remains a multidisciplinary challenge. Here, distinctive functional carbon dots derived from carbonized Platycladus orientalis (CPO-CDs) are developed using one-step hydrothermal method. The negatively charged surface of CPO-CDs retains partial functional groups from CPO precursor, exhibiting excellent water solubility and high biocompatibility. Both rat liver injury model and tail amputation model have confirmed the rapid and effective hemostatic performance of CPO-CDs on exogenous hemorrhage. Further, on endogenous blood-heat hemorrhage syndrome rat model, CPO-CDs could inhibit hemorrhage and alleviate inflammation response. Interestingly, the excellent hemostasis performance of CPO-CDs is ascribed to activate exogenous coagulation pathway and common coagulation pathway. More importantly, metabolomics of rat plasma suggests that the hemostasis effect of CPO-CDs is closely related to platelet functions. Therefore, the designed in vitro experiments are performed and it is discovered that CPO-CDs significantly promote platelets adhesion, activation, and aggregation. Further, the underlying mechanism investigation suggests that Src/Syk signal pathway plays a key role in platelets activation triggered by CPO-CDs. Overall, CPO-CDs with rapid and excellent hemostatic performance are discovered for the first time, which could be an excellent candidate for the treatment of hemorrhagic diseases.

Imaging features of sentinel lymph node mapped by multidetector-row computed tomography lymphography in predicting axillary lymph node metastasis.

INTRODUCTION: Accurately assessing axillary lymph node (ALN) status in breast cancer is vital for clinical decision making and prognosis. The purpose of this study was to evaluate the predictive value of sentinel lymph node (SLN) mapped by multidetector-row computed tomography lymphography (MDCT-LG) for ALN metastasis in breast cancer patients. METHODS: 112 patients with breast cancer who underwent preoperative MDCT-LG examination were included in the study. Long-axis diameter, short-axis diameter, ratio of long-/short-axis and cortical thickness were measured. Logistic regression analysis was performed to evaluate independent predictors associated with ALN metastasis. The prediction of ALN metastasis was determined with related variables of SLN using receiver operating characteristic (ROC) curve analysis. RESULTS: Among the 112 cases, 35 (30.8%) cases had ALN metastasis. The cortical thickness in metastatic ALN group was significantly thicker than that in non-metastatic ALN group (4.0 ± 1.2 mm vs. 2.4 ± 0.7 mm, P < 0.001). Multi-logistic regression analysis indicated that cortical thickness of > 3.3 mm (OR 24.53, 95% CI 6.58-91.48, P < 0.001) had higher risk for ALN metastasis. The best sensitivity, specificity, negative predictive value(NPV) and AUC of MDCT-LG for ALN metastasis prediction based on the single variable of cortical thickness were 76.2%, 88.5%, 90.2% and 0.872 (95% CI 0.773-0.939, P < 0.001), respectively. CONCLUSION: ALN status can be predicted using the imaging features of SLN which was mapped on MDCT-LG in breast cancer patients. Besides, it may be helpful to select true negative lymph nodes in patients with early breast cancer, and SLN biopsy can be avoided in clinically and radiographically negative axilla.

Global Epidemiologic Trends and Projections to 2030 in Non-Rheumatic Degenerative Mitral Valve Disease from 1990 to 2019: An Analysis of the Global Burden of Disease Study 2019.

Background: No studies have updated the epidemiologic changes in non-rheumatic degenerative mitral valve disease (DMVD) since 2019, thus this study utilized data from the Global Study of Diseases, Injuries, and Risk Factors 2019 (GBD2019) to assess the burden of DMVD in 204 countries and territories over the period 1990-2019, as well as changes in the prevalence, incidence, deaths and changes in disability-adjusted life years (DALYs). Methods: Using the results from the GBD2019, analyzing the incidence, prevalence, deaths, and DALYs rates, as well as their age-standardized rates (ASR). Based on the human development index (HDI), the socio-demographic index (SDI), age, and sex. Results: In 2019, there were 24.229 million (95% uncertainty interval (UI) 23.081-25.419 million) existing cases of DMVD worldwide, with 1.064 million (95% UI 1.010-1.122 million) new cases and 0.034 million (95% UI 0.028-0.043 million) deaths, and 0.883 million (95% UI 0.754-1.092 million) disability-adjusted life years. The incidence, prevalence, deaths, and DALYs of DMVD and their ASR showed significant differences across sex, age groups, regions, and countries from 1990 to 2019. It is projected that by 2030, the incidence of DMVD in females will be 0.72 million with an ASR of 15.59 per 100,000 population, 0.51 million in males with an ASR of 11.75 per 100,000 population, and a total incidence of 1.23 million with an ASR of 14.03 per 100,000 population. Conclusions: DMVD remains a significant public health problem that cannot be ignored, despite a decreasing trend in the ASR of global incidence, prevalence, deaths and DALYs from 1990 to 2019. However, we note an adverse development trend in countries with low socio-demographic indexes and seriously aging societies, and sex inequality is particularly prominent. This indicates the need to reposition current prevention and treatment strategies, with some national health administrations developing corresponding strategies for preventing an increase in DMVD based on local health, education, economic conditions, sex differences, and age differences.

Macrophages induce AKT/ß-catenin-dependent Lgr5+ stem cell activation and hair follicle regeneration through TNF.

Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen-anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro. TNF-induced ß-catenin accumulation is dependent on AKT but not Wnt signalling. Inhibition of PI3K/AKT blocks depilation-induced HF TAT. Notably, Pten loss in Lgr5+ HF stem cells results in HF TAT independent of injury and promotes HF neogenesis after wounding. Thus, our results suggest that macrophage-TNF-induced AKT/ß-catenin signalling in Lgr5+ HF stem cells has a crucial role in promoting HF cycling and neogenesis after wounding.

Combination of celecoxib and doxorubicin increases growth inhibition and apoptosis in acute myeloid leukemia cells.

Cyclooxygenase-2 (COX-2) inhibitors have been shown to enhance antitumor activity of therapeutic agents in a variety of solid tumor cells. However, this has not been well established in hematopoietic tumors, especially in acute myeloid leukemia (AML). This study was designed to investigate the effects of the combination of celecoxib, a specific COX-2 inhibitor, and doxorubicin on cell growth and apoptosis in human leukemia cells. Co-treatment with celecoxib and doxorubicin significantly inhibited cell growth and induced cell apoptosis in the acute leukemia cell line HL60 and primary AML cells. The growth inhibition effect was accompanied by down-regulation of the expression of cyclin E and cyclin-dependent kinase 2 (CDK2), the key regulators of cell cycle progression, which was associated with arrest of cells at G0/G1 phase. The pro-apoptotic effect was accompanied by down-regulation of the expression of survivin, an inhibitor of apoptosis protein, which mediated anti-apoptosis in AML cells. These results provide the first evidence that the growth inhibitory and pro-apoptotic effects of celecoxib and doxorubicin on AML cells are synergistic.

Human genome-specific real-time PCR method for sensitive detection and reproducible quantitation of human cells in mice.

Xenotransplantation of human cells into immunodeficiency mice has been frequently used to study stem cells in tissue repair and regeneration and cancer cell metastasis. However, a sensitive and reproducible method to quantify cell engraftment lacks. Here, we developed a Real-Time PCR-based method which facilitated consistent detection and quantification of small amounts of human cells distributed in mouse organs after infusion. The principle of the method was to directly detect a humans-specific sequence in the human-murine genomic DNA mixture. In a mouse myocardial infarction model, the Real-Time PCR-based method consistently determined the amounts of human mesenchymal stem cells (hMSCs) engrafted into the heart and other organs 7 days after infusion of as little as 2.5 × 10(5) cells, indicating a high sensitivity, and the amounts of hMSCs detected in mice highly correlated to the numbers of hMSCs transplanted. Importantly, different from previous PCR-based methods, our method produced highly consistent and reproducible results. The reliability of the method was further proven by parallel analyses of DiI-labeled hMSCs in tissue sections and in single cell suspensions of mice. Our data show that the present human genomic DNA-specific primers-based Real-Time PCR method is sensitive and highly reproducible in determining the amount of xenotransplanted human cells in murine tissues.