Patients with metastatic castration-resistant prostate cancer (mCRPC) face poor prognoses due to tumor heterogeneity and drug resistance. Antibody-drug conjugates (ADCs) have been under development for over two decades for mCRPC treatment. Several clinical trials have demonstrated promising antitumor activity and acceptable safety profiles for ADCs in this setting. Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 and DXC008 (both dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, an international multicenter phase Ⅲ clinical trial (NCT06925737) for mCRPC has been initiated in May 2025 for evaluating B7-H3-targeted ADC ifinatamab deruxtecan. This review summarizes recent advances in ADCs targeting key antigens in mCRPC (including PSMA, B7-H3, STEAP1, TROP2, SLC44A4, and others) and explores combination strategies, offering insights to inform the clinical management of mCRPC.
Humans ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Male ; Immunoconjugates/therapeutic use* ; Glutamate Carboxypeptidase II/immunology* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; B7 Antigens/immunology* ; Neoplasm Metastasis ; Prostate-Specific Antigen ; Antigens, Neoplasm/immunology* ; Antigens, Surface ; Camptothecin/analogs & derivatives* ; Oxidoreductases

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To explore the predictive value of 3D quantitative shape features based on enhanced CT for disease-free survival(DFS)of primary gastric gastrointestinal stromal tumors(GIST)patients receiving curative resection.Methods From January 2010 to December 2016,a total of 154 patients with primary gastric GIST who received curative resection in Zhongshan Hospital,Fudan University were retrospectively collected.The conventional CT imaging features and 3D quantitative shape features of tumors were evaluated,and the influencing factors of DFS were analyzed by univariate and multivariate Cox regression.Cut-off values were extracted,and Kaplan-Meier curves were used for survival analysis.Results Maximum 3D diameter(HR=1.829,95% CI 1.389-2.408,P＜0.001)and spherical disproportion(HR=2.153,95% CI 1.474-3.146,P＜0.001)were independent risk factors for DFS in primary gastric GIST.Kaplan-Meier curves showed that patients with maximum 3D diameter＞90.5 mm and spherical disproportion＞1.5 showed shorter DFS after curative resection(P＜0.001).Conclusion Maximum 3D diameter and spherical disproportion based on preoperative enhanced CT are valuable in the diagnosis of postoperative DFS in primary gastric GIST.

To explore the application of humanistic care in children's fever clinics,the children's fever clinics of Guangzhou Women and Children's Medical Center conducted relevant research using narrative medicine as a guiding concept.This paper elaborated on the medical humanistic dilemmas and narrative care needs in children's fever clinics,and focused on exploring the practice paths of narrative medicine in pediatric with Chinese characteristics from five dimensions,including the cultivation of nursing staff's abilities of professional narrative and humanistic care,the establishment of health lectures featuring narrative patient education,the alleviation of medical anxiety for children and their families,related support of narrative nursing,and caring services.The aim was to improve the narrative care ability of nurses in children's fever clinics,develop methods for pediatric patients that can eliminate the fear of seeking medical treatment,and protect children's physical and mental health.A carrier of care,support,and emotional expression can be provided for parents.The foundation for nursing staff to achieve professional growth through narrative reflection can be laid.Thus,it can assist in establishing a life narrative community relationship between doctors and patients,and jointly explore the meaning of life.

Objective To investigate the predictive efficacy of serum aminoterminal brain natriuretic pep-tide precursor(NT-proBNP),hypersensitive C-reactive protein(hs-CRP),D-dimer(D-D)and procalcitonin(PCT)in heart failure after acute myocardial infarction(AMI),Methods A total of 100 AMI patients admit-ted to the hospital from July 2021 to July 2023 were enrolled in the study as the observation group,In addi-tion,100 healthy people who underwent physical examination in the hospital during the same period were en-rolled as the control group,The serum levels of NT-proBNP,hs-CRP,D-D and PCT were detected and com-pared between the observation group and the control group,The AMI patients enrolled in the study were fur-ther divided into the heart failure group(31 cases)and the non-heart failure group(69 cases)according to the presence or absence of heart failure.The serum levels of NT-proBNP,hs-CRP,D-D,and PCT were compared between the two groups,Univariate analysis and multivariate Logistic regression analysis were used to analyze the risk factors of heart failure after AMI,Receiver operating characteristic(ROC)curve and decision curve a-nalysis(DCA)were used to analyze the predictive efficacy of serum NT-proBNP,hs-CRP,D-D and PCT for heart failure after AMI.Results The levels of serum NT-proBNP,hs-CRP,D-D and PCT in the observation group were higher than those in the control group(P＜0.05).The serum levels of NT-proBNP,hs-CRP,D-D and PCT in the complicated heart failure group were higher than those in the non-heart failure group(P＜0.05),Body mass index(BMI),smoking history,hypertension,number of diseased vessels,serum uric acid(SUA),low-density lipoprotein cholesterol(LDL-C),NT-proBNP,hs-CRP,D-D and PCT were risk factors for heart failure after AMI(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of combined detection of serum NT-proBNP,hs-CRP,D-D and PCT for predicting heart failure after AMI was 0.857(95％CI:0.811-0.948),the sensitivity was 96.12％,and the specificity was 91.28％,which were higher than the corresponding efficacy indexes of single detection(P＜0.05).DCA analysis showed that when the high-risk threshold was 0-0.99,the net benefit rate was greater than 0,which had clinical significance,When the threshold was 0-0.76,the net benefit rate of combined detection of serum NT-proBNP,hs-CRP,D-D and PCT was better than that of serum NT-proBNP,hs-CRP,D-D and PCT alone.Conclusion Combined detection of serum NT-proBNP,hs-CRP,D-D and PCT can improve the predictive efficiency of AMI compli-cated with heart failure,BMI,smoking history,hypertension,number of diseased vessels,SUA,LDL-C,NT-proBNP,hs-CRP,D-D and PCT are risk factors for AMI complicated with heart failure.

Purpose/Significance To apply the 5G ward round robot platform in primary hospitals,so as to effectively improve the treatment capability and management service level of patients with critical and severe diseases.Method/Process Based on technologies such as 5 G,internet of things(IoT)and robotics,the researchers build and deploy a 5 G ward round robot platform and collaborate with domestic experts to provide mobile ward round,remote consultation,intensive care,health education and other services for patients.Re-sult/Conclusion Real time sharing of patient clinical data and efficient collaboration in the diagnosis and treatment process can be a-chieved,multi-mode,accurate and standardized remote ward round and treatment guidance can be carried out according to patients'conditions.

Objective To achieve personalized assessment of cumulated activity distribution in patients undergoing 18F-FDG PET scans using the biokinetic model based on the single-time-point PET images.Methods A biokinetic compartmental model for the organs of interest was established,and the variation of activities in each compartment was described as a set of differential equations.The PET image data at a specific time point of each patient was used to obtain the kinetic model parameters which were then optimized by a simulated annealing algorithm to calculate the cumulated activity of each organ.Additionally,the effects of different voiding patterns on the cumulated activity of the bladder were analyzed.Considering the heterogeneity of radioactive nuclide distribution in organs,a whole-body cumulated activity distribution map was computed,and the accuracy of the proposed method was evaluated by comparison with the existing methods.Results For the 11 cases analyzed in the study,the calculation results of the biokinetic model generally showed a good agreement with experimental data,with an average deviation of less than 15%.Meanwhile,under different urinary excretion conditions,the average cumulated activity in the bladder differed by up to 2.4 times,indicating the positive significance of enforced urination in reducing radiation exposure.The comparison with the biokinetic data obtained from ICRP Publication 128 revealed relatively large deviations for certain organs such as the brain and heart,with standard deviations of 61.0%and 46.3%,respectively.Conclusion The constructed biokinetic model can effectively estimate the individualized cumulated activity distribution in patients undergoing PET scans,providing valuable insights for the internal dosimetry assessment.

Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.