Objective To develop a system achieving automated real-time tracking and localizing of tumor center in radiotherapy. Methods High-accuracy infrared tracking cameras' coordinate system was calibrated with the treatment machine. A kind of passive marker was introduced, which can be imaged by computed tomography and can be localized by the infrared cameras during radiotherapy. Several markers on the surface of the thermal-shaped film were fixed, and then the real-time co-ordinates of the markers was compared with those obtained from the computed tomography. With subsequent space registration, the position biases could be shown finally, which could help achieving the real-time tracking and localizing of the tumor center. Results With infrared tracking cameras and appropriate software, the system can achieve automated and real-time localization in radiotherapy. Conclusion The system is more automated, accurate and speedy than the traditional localization method.

Objective To investigate the morphological and proteomic differences in exosomes(EXOs)during the stor-age of leukocyte-free apheresis platelets(LFA-Plt),evaluate the quality of platelets in storage and predict the function of EXOs at different storage periods.Methods EXOs were isolated by ultracentrifugation,then the morphological observation was performed by electron microscope.Particle size analysis and WB protein index detection were performed.4D Label-free quantitative proteomics technology was used to perform quantitative and bioinformatics analysis on identified proteins.Protein differential analysis on the LFA-Plt EXO between group day 3 and day 5 was performed,and GO function and KEGG path-way enrichment analysis on differential proteins was conducted.Results Cup shaped,CD9/TSG101 enriched and Calnexin(-)EXO was successfully obtained.The particle size(nm)of LFA-Plt EXO for day 3 and day 5 were(82.2±19.6)and(83.4±19.4)respectively,and the protein concentration(μ g/uL)were(0.55±0.13)and(0.51±0.08)respectively,with no statistically significant difference between two groups(P＞0.05).1 504 proteins were identified in all samples.GO func-tional enrichment analysis showed that the LFA-Plt EXO proteins were mainly concentrated in the cell membrane,extracel-lular domain and proteasome core complex,and were related to the binding ability of proteins,ATP,calcium ions and GTP,and mainly participated in processes such as redox,protein hydrolysis and signal transduction.KEGG functional annotation showed that the EXO proteins mainly participated in material transportation and catabolism,genetic information processing,and were closely related to human tumors and viral bacterial infections,affecting the metabolism of human immune system.Compared with day 3,day 5 EXO showed significant up-regulation in 16 proteins.The GO enrichment analysis showed that 16 upregulated proteins were mainly associated with adenosine homocysteine activity and 6-phosphofructose kinase activity,and were mainly involved in the metabolism of organic nitrogen compound.KEGG enrichment pathway analysis showed that the most important function of upregulated proteins was participating in signaling pathway for oocyte maturation mediated by progesterone.Conclusion Under the preparation and storage conditions of LFA-Plt in our center,platelet quality can be relatively stable.The functions of EXO proteins varies with different storage periods,which may affect the effectiveness of platelet transfusion.

Objective To explore the value of multi-modal MRI in the differential diagnosis of pure fibroadenosis and mixed fibroadenosis in the breast. Methods Forty female patients who underwent 3.0 T MRI within 1 week before sugery and confirmed as breast fibroadenosis by pathology in the General Hospital of the PLA Rocket Force from January 2014 to May 2016 were retrospectively analyzed in this study. There were 20 cases of pure fibroadenosis which including mass type and non-tumor type, 10 cases per type. Twenty cases of mixed fibrous adenosis which including 4 cases of mass type and 16 cases of non-mass type. According to the breast imaging reporting and data system-MRI standard, conventional MRI features, time intensity curve (TIC) types and ADC values of the lesions were observed. MRI features and ages of pure fibroadenosis and mixed fibroadenosis were compared using χ2 test (qualitative data) and independent sample t test (quantitative data), P<0.05 was considered statistically significant. Statistically significant parameters were then used to perform logistic regression analysis to evaluate predictive value . The efficacy of each MRI parameter in the differential diagnosis of pure fibroadenosis and mixed fibroadenosis was analyzed by ROC. Results Statistically significant differencein the size(P<0.05) but no differences in the shape, T2WI manifestation, marginal, internal enhancement, early enhancement curve, and late enhancement (P>0.05) were observed between pure fibroadenosis and mixed fibroadenosis. There was no significant differences in distribution, internal enhancement, early enhancement curve and late enhancement curve between non-tumor type pure fibroadenosis and mixed fibroadenosis (P>0.05). There were significant differences in age, ADC value and peak signal intensity(P<0.05) while no significant differences in early enhancement rate, maximum enhancement rate and peak time (P>0.05) between patients with pure fibroadenosis and mixed fibroadenosis. Logistic regression analysis suggested that the peak signal intensity was closely related to age. It revealed a positive correlation between ADC value, peak signal intensity and the possibility of mixed fibroadenosis. The regression coefficient value, Wals value, and P value of the ADC value were 3.652, 4.363 and 0.034, respectively. The regression coefficient value, Wals value, and P value of the peak signal intensity were 0.005, 5.463 and 0.019, respectively. The area under ROC curve of ADC value, peak signal intensity, ADC value combined with peak signal intensity were 0.697, 0.701 and 0.786, respectively. Conclusions Significantly differences of peak signal intensity and ADC value were observed in mixed fibroadenosis compared with pure fibroadenosis. The combination of ADC value and peak signal intensity had the highest efficacy in predicting pure and mixed fibroadenosis.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

OBJECTIVE： To optimize the processing technology of fried Radix Paeoniae， and to provide reference for quality control of the processed products. METHODS： The content of paeoniflorin in fried Radix Paeoniae was determined by HPLC. The determination was performed on Agilent ZORBAX SB-C18 column with mobile phase consisted of acetonitrile-0.05 mol/L potassium dihydrogen phosphate solution （15 ∶ 85， V/V） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃， and detection wavelength was set at 230 nm. The sample size was 10 μL. The appearance character of fried Radix Peaoniae were investigated by appearance color， crosssection color， hardness and smell. Taking the comprehensive score of appearance character and paeoniflorin content as evaluation index， the dosage， stir-frying temperature and stir-frying time were investigated. According to the results of single factor test， Box-Behnken response surface methodology was used to optimize above 3 factors. The optimized processing technology was validated. RESULTS： The linear range of paeoniflorin were 0.02-4.15 mg/mL （r＝0.999 9）； precision， stablity， repeatability and sample recovery rate meet the requirements. The optimal technology of fried Radix Paeoniae included the dosage of 374.60 g， frying temperature of 101.61 ℃， frying time of 20 min. Under optimal technology， comprehensive score of fried Radix Paeoniae ranged 97.39-98.82 in 6 times of parallel verification tests （RSD＝0.54％）， which was close to predicted value 98.18. The color of fried Radix Paeoniae was slightly deeper than Radix Paeoniae， which was crisp and fragrant. CONCLUSIONS： The optimized processing technology of fried Radix Paeoniae is stable and feasible， and is suitable for the preparation of the processed products.