The 1St Affiliated Hosp of Guangdong Pharm University

Diabetic nephropathy (DN) is a diabetes mellitus (DM)-induced complication that poses high morbidity and mortality risks. The Astragalus and Salvia miltiorrhiza couplet medicines (AS) are commonly employed in DN clinical treatment in China, but their clinical efficacy and potential pharmacological mechanisms are yet to be evaluated.

A meta-analysis of 15 studies involving 1,443 patients was conducted. Furthermore, network pharmacology predicted components and targets, which were verified by molecular docking and in vivo validation.

In our meta-analysis, AS notably elevated clinical outcomes and renal function among patients with DN. Meanwhile, when the treatment duration exceeds 12 weeks, AS demonstrated a significant reduction in fasting blood glucose levels, indicating a time-dependent effect. Moreover, based on network pharmacology results, AS likely enhanced clinical outcomes by interacting with vital signaling pathways, including PI3K/Akt, MAPK, and NF-kappa B. Molecular docking studies have confirmed that PTGS2, the key therapeutic target of AS, can be closely combined with bioactive components GLY, quercetin, apigenin, and daidzein. Additionally, in vivo experiments have corroborated that AS can ameliorate renal function, UACR, and biomarkers associated with iron metabolism, such as GPX4, PTGS2, FTH1, and FTL1.

Through rigorous experimental validation, our study demonstrates AS's significant clinical efficacy in managing DN. Specifically, AS has been shown to enhance renal function, ameliorate renal fibrosis, and positively influence iron metabolism. Despite these promising outcomes, future research with a larger sample size must be conducted to further substantiate these findings.

Existing literature highlights the benefits of organizational climate, but research gaps exist regarding how a patient-oriented organizational climate captures the sub-dimensions of physicians' patient-centered behavior. We explored the mediating role of patient-centeredness self-efficacy between them.

Utilizing the Patient-Oriented Organizational Climate Scale, Self-efficacy in Patient-Centeredness Questionnaire, and Doctor Interaction Behavior Evaluation Scale, we surveyed 1394 physicians from grade ⅢA general hospitals in Guangdong Province, China from July to September 2022, employing stratified proportional sampling.

Patient-oriented organizational climate was positively associated with patient-centered behavior. Patient-centeredness self-efficacy partially mediated their relationship, with varying effects on different dimensions of patient-centered behavior; further, it could partially mediate the association between patient-oriented organizational climate and dialogue and transparency dimensions, but played a full mediating role between patient-oriented organizational climate and access and risk assessment dimensions.

These findings underscore the importance of establishing a patient-oriented organizational climate and fostering patient-centeredness self-efficacy in shaping patient-centered behavior, as they differ in impact on the dimensions of patient-centered behavior.

Targeted interventions are necessary to clarify the definitions of patient-centered behavior and consider it as a multidimensional construct.

At the heart of cancer pathology lies the dysregulated cell cycle, which is often driven by aberrant activities of the cell cycle regulating, cyclin-dependent kinases (CDKs). Efforts to harness the therapeutic potential of modulating CDK activities have led to the development of inhibitors with tailored CDK selectivity. However, uniformity in the methods used to evaluate CDK inhibitor selectivity has been lacking and consequently, direct comparison and interpretation of selectivity profiles determined under different assay conditions is difficult. Determination of the inhibition modalities crucial to profiling selectivity of a CDK inhibitor requires thorough kinetic analysis carried out under comparable assay conditions. In this study, we employed a streamlined series of in vitro assays for profiling CDK inhibitors wherein intrinsic inhibition constants and cellular binding parameters were measured by using strategically designed enzymatic inhibition and complementary biophysical assays. Our findings demonstrate the effectiveness of this strategy in determining and quantitatively analyzing the selectivity and inhibition modality of a set of representative CDK inhibitors towards the major oncogenic, cell cycle CDKs. In addition, the assay results provide insights into the inhibitor-target interactions that extend beyond potency and selectivity.