ABSTRACT
Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.
ABSTRACT
Objective To explore the scientificity and feasibility of using weighted rank-sum ratio (RSR) method based on diagnosis-related groups ( DRGs) indicators in nursing performance evaluation. Methods Homepage data of medical records were extracted from inpatients discharged in 2017, and " CN-DRGs" burster was used to obtain the DRGs data. Data of medical safety were obtained from the nursing adverse event management system, while data of nursing grading information and medical expenses were obtained from the hospital information system, and the patient satisfaction was obtained in a questionnaire survey. Based on the indicators available, the weighted RSR was applied to evaluate the nursing performance from the 11 dimensions, namely workload, nursing competence, nursing quality, nursing personnel allocation, patient satisfaction, etc. Results The results of the weighted RSR showed that 43, 39, and 6 wards of total 88 wards of the hospital were rated as excellent, medium and poor grades respectively. The results of ANOVA showed that the difference of the 3 grades was significant (F=170. 391, P<0.001). The nursing performance evaluation results were consistent with the actual situation. Conclusions The evaluation of nursing performance with weighted RSR method based on DRGs indicators prove its practical application value, as this method can not only provide data support for nursing personnel allocation, but also provide reference for nursing quality evaluation and supervision.
ABSTRACT
The paper follows the preparation rules of health information data element standards,studies the catalog of statistical data element of Traditional Chinese Medicine (TCM) and the preparation contents,ideas and methods of value field code,prepares and forms Comprehensive Statistical Data Element Dictionary of Traditional Chinese Medicine and Classification and Coding for Value Domain of Comprehensive Statistical Data Element of Traditional Chinese Medicine,so as to provide reference standard and basis for the standardization and informatization in the statistical field of TCM.