Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

Single-cell analysis of phenotypic plasticity could improve the development of more effective therapeutics. Still, the development of tools to measure single-cell heterogeneity has lagged due to difficulties in manipulating and culturing single cells. Here, we describe a single-cell culture and phenotyping platform that employs a starburst microfluidic network and automatic liquid handling system to capture single cells for long-term culture and multi-dimensional analysis and quantify their clonal properties via their surface biomarker and secreted cytokine/growth factor profiles. Studies performed on this platform found that cells derived from single-cell cultures maintained phenotypic equilibria similar to their parental populations. Single-cell cultures exposed to chemotherapeutic drugs stochastically disrupted this balance to favor stem-like cells. They had enhanced expression of mRNAs and secreted factors associated with cell signaling, survival, and differentiation. This single-cell analysis approach can be extended to analyze more complex phenotypes and screen responses to therapeutic targets.

Purpose To compare the 5.0T gradient echo coronary magnetic resonance angiography(CMRA)using compressed sensing(CS)acceleration technology(5.0TCS-CMRA)vs.3.0T gradient echo-CMRA(3.0TCS-CMRA)using CS.Materials and Methods Twenty-five healthy volunteers aged 23 to 30 years from December 16,2023 to January 14,2024 at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences were prospective enrolled in this study.The interval between 3.0TCS-CMRA and 5.0TCS-CMRA was within two weeks.3.0TCS-CMRA used T2 preparation and 5.0TCS-CMRA did not use T2 preparation.The image quality scores,coronary artery length,signal-to-noise ratio(SNR)and contrast-to-noise ratio between coronary blood and adjacent myocardium or tissue(CNRmyo-blood)were evaluated.Results On 5.0TCS-CMRA,the SNR and CNRmyo-blood of the proximal right coronary artery(RCA)in 25 healthy volunteers were significantly higher than those of 3.0TCS-CMRA(SNR:318.07±94.06 vs.223.81±51.19,t=-5.609,P<0.001;CNRmyo-blood:212.75±91.44 vs.149.70±59.53,Z=-3.619,P<0.001),while the SNR and CNRmyo-blood of proximal left anterior descending coronary artery(LAD)and left circumflex coronary artery(LCX)were not significantly higher than those of 3.0TCS-CMRA(SNR:315.52±102.49 vs.306.35±92.85,t=-0.627,P=0.536;289.72±88.79 vs.272.87±84.68,t=-1.226,P=0.232;CNRmyo-blood:135.83±93.53 vs.203.94±74.30,t=4.132,P<0.001;117.66±79.63 vs.161.60±78.91,t=3.127,P=0.005).The length of the three coronary arteries measured by 5.0TCS-CMRA was significantly shorter than that of 3.0TCS-CMRA[RCA:(126.04±31.54)mm vs.(137.20±29.93)mm,t=2.911,P=0.008;LAD:(122.68±24.63)mm vs.(134.24±23.38)mm,Z=-3.026,P=0.002;LCX:(57.07±26.70)mm vs.(68.27±24.02)mm,t=2.552,P=0.018].There was no significant difference in the scanning time required between 3.0TCS-CMRA and 5.0TCS-CMRA[(8.60±2.84)min vs.(8.30±2.32)min,Z=-0.183,P=0.855].The image scores of the three major coronary arteries of 5.0TCS-CMRA were significantly lower than those of 3.0TCS-CMRA(RCA:2.52±0.59 vs.3.16±0.69,Z=-3.258,P=0.001;LAD:2.72±0.74 vs.3.24±0.66,Z=-2.540,P=0.011;LCX:2.44±0.71 vs.3.00±0.87,Z=-2.462,P=0.014).Conclusion In the absence of T2 preparation,5.0TCS-CMRA can still show obvious advantages in the SNR and CNRmyo-blood of proximal RCA compared with 3.0TCS-CMRA,which suggests the application potential of 5.0TCS-CMRA.In the future,a suitable T2 preparation pulse or potential alternative may significantly improve the performance of the 5.0TCS-CMRA.

Objective:To study the functional characteristics of protective,barrier,and controlled release of film forming pharmaceutical excipients in formulations,establish a method for measuring the properties of film forming pharmaceutical excipients,and evaluate their performance.Methods:By preparing free films of different film forming pharmaceutical excipients and referring to national standards and literature research systems,a testing sys-tem covering key indicators such as tensile strength and elongation,water vapor permeability,flexibility,and solu-bility was constructed.Results:Through comparative testing of multiple brands of excipients,all detection methods showed good discriminability and reproducibility,indicating the applicability and stability of the methods.Conclusion:Evaluating the properties of film forming pharmaceutical excipients through a successfully constructed method not only reveals the structure-activity relationship between material structure and functional characteristics,but also provides technical support for the construction of functional index databases for pharmaceutical excipients.This research result can be used to guide the development of new film forming pharmaceutical excipients and pro-vide experimental basis for industry standard setting,meeting the needs of drug research and quality supervision.

Objective:To study and establish the quality standard of Polyoxyl 15 hydroxystearate(HS15),a phar-maceutical excipient,and systematically evaluate its functionality-related characteristics and safety.HS15 was applied to the preparation of docetaxel(DTX)injection to further investigate the safety and pharmacokinetic char-acteristics of the injection in vitro and in vivo.Methods:Based on the general USP-NF2024,EP11.0 and the fourth general rules of the Chinese Pharmacopoeia 2020 edition,the quality standards of HS15 were studied.Combined with the functional properties of surfactants,the critical micelle concentration of HS15 was investigated,and its safety was investigated by hemolysis test and vascular irritation test in vitro.HS15 was further applied to the preparation of DTX injection,and the safety and efficacy of the preparation were comprehensively evaluated by in vitro cytotoxicity test and in vivo pharmacokinetic study.Results:According to the experimental results and the pharmacopoeia of various countries,the quality standard of HS15 was preliminarily formulated.When the concen-tration of HS15 was 1 mg·mL-1,the hemolysis rate was about0.2%,the vascular irritation was small,and the DTX injection was safe in vitro and in vivo.The pharmacokinetic behavior was in line with expectations.Conclusion:This study successfully established the quality standard of HS15,and its functional correlation index research and safety evaluation strategy can provide reference for the quality control of similar excipients.The appli-cation of HS15 in the preparation of DTX injection provides a theoretical and experimental basis for its application in the development of insoluble antitumor drug injection.

Objective:To establish a method for evaluating the material attributes and skeletal performance of 2208 hydroxypropyl methylcellulose(HPMC),to clarify the influence of different material attributes on the skeletal per-formance of HPMC,to compare the differences between the products of different manufacturers,and to analyze the factors affecting the process.Methods:In this study,the material attributes such as powder chemical properties,viscosity,gelation temperature,thermodynamic properties,weight-average molecular weight,methoxy and hydroxypropoxy contents of different manufacturers were firstly investigated.Then,the water absorption,swelling,and dissolution properties of HPMC blank skeleton tablets were determined using the weighing method.Finally,Principal Component Analysis(PCA)and Orthogonal Partial Least-Squares Discrimination Analysis(OPLS-DA)were used to systematically evaluate the material attributes and skeleton performance of HPMC.The systematic evaluation of each material attribute and skeleton performance of HPMC was carried out to elucidate the intrinsic relationship between each material attribute and skeleton performance of HPMC.Results:The results showed that there were obvious differences in the material attributes of HPMC from different manufacturers,such as the proper-ties of powder,viscosity,and weight-average molecular weight,and that there were differences in the corrosion performance,water absorption,and swelling performance of the skeleton tablets prepared from different manufactur-ers,with the most obvious differences between K4Mand K100M.The results of the PCA and OPLS-DA analyses indicated that these 19 variables showed some correlation with each other.Both mathematical models showed better differentiation and classification effects on HPMC samples,and the OPLS-DA model had better classification effects than the PCA model.Conclusion:Based on the PCA and OPLS-DA models,this study conducted systematical research on HPMC,clarified the degree of influence of different material attributes on the skeletal performance of HPMC,and suggested the addition of HPMC particle size and size distribution,and weight-average molecular weight as the quality standards,which provide a basis for the quality control of the related excipients,the screening of formulation prescriptions,and the improvement of performance.