Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

Drug therapy is a common method to cure diseases and relieve symptoms.The value of patient-reported outcome(PRO)in evaluating the effect of drug therapy has been increasingly paid attention.The PRO scale is a standardized questionnaire,which can scientifically evaluate the experiences and subjective effects of drug use from a patient-centered perspective,and help patients and clinicians make more reasonable medication decisions.By reviewing and sorting out relevant global literature,this paper found that the content of the PRO scales relevant to drug therapy focused on five fields:"medication satisfaction""medication adherence""drug treatment burden""medication-related quality of life"and"adverse drug reactions".This paper described the basic information,measurement characteristics and application of common scales in recent years respectively,and summarized and analyzed the problems and enlightenment of scale development,aiming to provide theoretical reference for the selection,application and development of PRO scales.

【Objective】 To explore the application value of free prostate specific antigen density(fPSAD) based on rectal ultrasound in the prediction of prostate biopsy results. 【Methods】 Data of 578 patients undergoing transrectal ultrasound guided prostate biopsy during Jan.2014 and Jul.2021 were retrospectively analyzed, including prostate specific antigen(PSA) level, free prostate specific antigen(fPSA) level, fPSA/total prostate specific antigen(tPSA), prostate specific antigen density(PSAD), combined prostate specific antigen density(cPSAD), fPSAD, prostate volume and other clinical parameters. 【Results】 There were 253 cases of prostate cancer and 325 cases of prostatic hyperplasia. The positive puncture rate was 43.8%. The critical value of fPSAD was 0.05, the corresponding area under receiver operating characteristic (ROC) curve was 0.830, and the Yoeden index was 0.539. The sensitivity, specificity, diagnosis accordance rate and Kappa value of fPSAD to predict prostate cancer were 0.76, 0.77, 76.7% and 0.529, respectively. Compared with PSA, fPSA/tPSA and PSAD, PSA had the highest sensitivity (92.5%), fPSAD had the highest specificity (77.2%), and fPSAD had the highest diagnostic accordance rate (76.7%). 【Conclusion】 When transrectal prostate volume measurement is used to predict prostate cancer, fPSAD has relatively high specificity and diagnosis accordance rate, which is obviously better than using PSA, fPSA/tPSA ratio and PSAD alone in the differential diagnosis and prediction of prostate cancer and prostatic hyperplasia.

Correspondence between man and nature theory is the core of TCM chronomedicine, and also plays an important role in ancient Chinese philosophy. The theory believes that distinguishing the rhythm is the foundation of treatment; complying with nature is the core of treatment; taking advantage of wane and wax is the method of treatment. This article combined the physiological and pathological characteristics of children to review the prevention and treatment of pediatric diseases based on chronomedicine, with a purpose to provide inspirations for clinical treatment.