Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

Objective:To establish a nomogram to predict overall survival(OS)of Uterine carcinosarcoma(UCS)patients.Methods:A total of 2635 UCS patients were selected from the Surveillance,Epidemiology and End Results(SEER)database between 2000 and 2020.The patients were randomly divided into a training cohort and a validation cohort in a 7∶3 ratio.Univariate Cox regression analysis,Lasso regression and multivariate Cox analysis was conducted to screen for independent risk factors affecting OS in UCS patients.We established a no-mogram for predicting the 1-and 3-year OS of UCS patients and evaluate the discrimination and calibration of the nomogram using receiver operating characteristic curve(ROC),calibration plots and decision curve analysis(DCA).According to the nomogram scores,patients were divided into low,medium,and high-risk groups and compared with the International Federation of Gynecology and Obstetrics(FIGO)staging system.Results:Age,race,tumor size,tumor stage,surgery,radiotherapy,chemotherapy and lymph node metastasis were identified as independent prognostic factors affecting patient OS(P＜0.05),and the above eight key variables were selected to establish the nomogram for predicting 1-and 3-year OS in UCS patients.The C-index and the area under the ROC curve(AUC)values of both the training and validation cohorts were greater than 0.7,indicating good discriminative capabilities of the nomogram.The calibration curves showed high consistency between the predicted probability and actual survival results.Moreover,the DCA curves suggested the clinical utility and application value of the model were superior to those of the FIGO staging system.The total risk score of each patient was calculated ac-cording to the nomogram model.UCS patients were divided into the low-risk group(score＜80),middle-risk group(score 80-130),and high-risk group(score＞130).Kaplan-Meier survival analysis demonstrated that the nomo-gram had a good ability to identify high-risk individuals.Conclusions;The model is a useful tool for accurately predicting OS in UCS patients and can assist in making individualized interventions by providing valuable prognos-tic information.

Objective:To establish a nomogram to predict overall survival(OS)of Uterine carcinosarcoma(UCS)patients.Methods:A total of 2635 UCS patients were selected from the Surveillance,Epidemiology and End Results(SEER)database between 2000 and 2020.The patients were randomly divided into a training cohort and a validation cohort in a 7∶3 ratio.Univariate Cox regression analysis,Lasso regression and multivariate Cox analysis was conducted to screen for independent risk factors affecting OS in UCS patients.We established a no-mogram for predicting the 1-and 3-year OS of UCS patients and evaluate the discrimination and calibration of the nomogram using receiver operating characteristic curve(ROC),calibration plots and decision curve analysis(DCA).According to the nomogram scores,patients were divided into low,medium,and high-risk groups and compared with the International Federation of Gynecology and Obstetrics(FIGO)staging system.Results:Age,race,tumor size,tumor stage,surgery,radiotherapy,chemotherapy and lymph node metastasis were identified as independent prognostic factors affecting patient OS(P＜0.05),and the above eight key variables were selected to establish the nomogram for predicting 1-and 3-year OS in UCS patients.The C-index and the area under the ROC curve(AUC)values of both the training and validation cohorts were greater than 0.7,indicating good discriminative capabilities of the nomogram.The calibration curves showed high consistency between the predicted probability and actual survival results.Moreover,the DCA curves suggested the clinical utility and application value of the model were superior to those of the FIGO staging system.The total risk score of each patient was calculated ac-cording to the nomogram model.UCS patients were divided into the low-risk group(score＜80),middle-risk group(score 80-130),and high-risk group(score＞130).Kaplan-Meier survival analysis demonstrated that the nomo-gram had a good ability to identify high-risk individuals.Conclusions;The model is a useful tool for accurately predicting OS in UCS patients and can assist in making individualized interventions by providing valuable prognos-tic information.

, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of remains obscure. In this study, to explore the active constituents of , we compared pharmacodynamics and chemical profiles / of EES/WES for the first time using multiple chemical analysis, pharmacological and data processing approaches. It was proved that there was no significant difference in the anti-depressive effects between WES and EES. However, the contents of most components and in plasma were higher in EES than those in WES, which was unconvincing for their similar efficacy. Therefore, we further explored components of targeted onto brain and the results showed that 5 lignans were identified with definite absorptivity respectively both in EES and WES caused by the limitation of blood-brain barrier. Moreover, bioinformatic analysis predicted their anti-depressive action. Above all, the systematic strategy screened 5 brain-targeted effective substances of and it was suggested that exploring the components into nidi would promote the studies on herbs effective material basis.