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

Objective:To investigate the incidence and influencing factors of allergic reactions to cephalosporins.Methods:A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021.The incidence of allergic reactions to cephalosporins was investigated,and the influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression.Results:A total of 56 155 patients were included in this study.The total incidence of allergic reactions to cephalosporin was 1.67‰,the highest incidence of anaphylaxis occurred for ceftizoxime(4.27‰),followed by ceftriaxone(3.49‰)and cefotaxime(2.40‰).There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests(1.75％o vs.1.63‰,RR=1.07,95％CI:0.70-1.63,P＞0.05).Poisson regression showed that body mass index(BMI)＜18.5 kg/m2(RR=2.43,95％CI:1.23-4.82,P＜0.05)and history of β-lactam antibiotics allergy(RR=33.88,95％CI:1.47-781.12,P＜0.05)increased cephalosporin-induced anaphylaxis.Compared with cefuroxime,the risk of allergic reactions was increased for ceftriaxone(RR=3.08,95％CI:1.70-5.59,P＜0.01),ceftazidime(RR=1.89,95％CI:1.03-3.47,P＜0.05),and ceftizoxime(RR=3.74,95％CI:1.64-8.50,P＜0.01).Conclusions:Lower BMI and history of β-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions.The routine skin test may not reduce the occurrence of allergic reactions to cephalosporins. This study has been registered at Chinese Clinical Trial Registry(ChiCTR2200064314).

Objective To explore the effectiveness of virtual autopsy-based postmortem computed tomography(PMCT)liver three dimensional slicer(3D slicer)artificial intelligence(AI)volume reconstruction to assist forensic practice.Methods Twenty cases of the deceased who underwent both virtual autopsy and traditional autopsy in our center were selected and subjected to liver volume segmentation by 3D slicer method,Tada's formula method and literature method,and the data obtained from the traditional autopsy were compared and analyzed to obtain the accuracy rate.Results The 3D slicer method yielded higher consistency(95%confidence interval),lower volumetric variability(standard deviation),and a smaller region(variance)of uncertainty than the Tada formula method and the methods mentioned in the literature.Conclusion 3D slicer AI reconstruction based on virtual autopsy can visualize virtual anatomy,help increase the diagnostic accuracy of traditional autopsy,assist in pathological diagnosis,and provide new directions and tools for the development of imaging histology of virtual autopsy.

OBJECTIVE: To establish the finite element model of varus-type ankle arthritis and to implement the finite element mechanical analysis of different correction models for tibial anterior surface angle (TAS) in supramalleolar osteotomy. METHODS: A female patient with left varus-type ankle arthritis (Takakura stage Ⅱ, TAS 78°) was taken as the study object. Based on the CT data, the three-dimensional model of varus-type ankle arthritis (TAS 78°) and different TAS correction models [normal (TAS 89°), 5° valgus (TAS 94°), and 10° valgus (TAS 99°)] were created by software Mimics 21.0, Geomagic Wrap 2021, Solidworks 2017, and Workbench 17.0. The 290 N vertical downward force was applied to the upper surface of the tibia and 60 N vertical downward force to the upper surface of the fibula. Von Mises stress distribution and stress peak were calculated. RESULTS: The finite element model of normal TAS was basically consistent with biomechanics of the foot. According to biomechanical analysis, the maximum stress of the varus model appeared in the medial tibiotalar joint surface and the medial part of the top tibiotalar joint surface. The stress distribution of talofibular joint surface and the lateral part of the top tibiotalar joint surface were uniform. In the normal model, the stress distributions of the talofibular joint surface and the tibiotalar joint surface were uniform, and no obvious stress concentration was observed. The maximum stress in the 5° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress distribution of medial tibiotalar joint surface was uniform. The maximum stress of the 10° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress on the medial tibiotalar joint surface increased. CONCLUSION With the increase of valgus, the stress of ankle joint gradually shift outwards, and the stress concentration tends to appear. There was no obvious obstruction of fibula with 10° TAS correction. However, when TAS correction exceeds 10° and continues to increase, the obstruction effect of fibula becomes increasingly significant.
Humans ; Female ; Tibia/surgery* ; Finite Element Analysis ; Ankle ; Arthritis ; Fibula/surgery* ; Ankle Joint/surgery*

Objective:To understand the current status of foreign dual-degree programs of Medical Doctor (MD) and Master of Public Health (MPH) and provide evidence-based decision-making reference for promoting the education of high-level applied public health talents in China.Methods:The list of involved institutions and information of foreign MD-MPH dual-degree programs was collected through literature retrieval, online information searching, and additional survey of key figures. We extracted the details of each project regarding professional fields, core competence, length of schooling, teaching and learning arrangement, internship eligibility, and graduation assessment. Python 3.8.0 was used for data cleaning, and the occurrence frequency of related items in each dimension was calculated.Results:A total of 99 MD-MPH programs from 104 foreign institutions were included, among which 97.1% of them were implemented in universities from the United States. The School of Public Health provided 42.4% (42/99) of the programs. Epidemiology was the major discipline set up among most programs, accounting for 12.0% (29/241) of all the specialties involved. Epidemiological research methods, health policy management and practice, and public health practice were the top 3 core competencies to be mastered. Of the 99 programs, 87 gave information on the length of the program, of which 74.7% (65/87) were five years, 6.9% (6/87) were four years, and 18.4% (16/87) included both 4-year and 5-year programs.Conclusions:The international MD-MPH programs were sophisticated and mainly organized by the School of Public Health alone or in conjunction with the School of Medicine. Epidemiology is the core course and competence objective, with a length of 4-5 years. Through learning experience from international MD-MPH programs and the Chinese unique medical development background, China should optimize its medical education system to develop a suitable talent training strategy for MD-MPH dual-degree programs in the new era.

Objective:To investigate the clinical characteristics and change trend of patients with perianal lesions before or after Crohn′s disease (CD) diagnosed.Methods:From January 2008 to September 2018, at The Tenth People′s Hospital Affiliated to Tongji University, the clinical data of 747 hospitalized CD patients were retrospectively collected, 293 patients were PCD patients. The clinical characteristics of PCD patients before or after CD diagnosed were analyzed and the change trend was followed. T test, Mann-Whitney U test, and Chi-square test were performed for statistical analysis. Multivariate logistic regression analysis was used to analyze factors associated with perianal lesions onset time. Spearman correlation analysis was used to analyze the change trend of clinical characteristics. Results:Before CD diagnosis, 86.3% (253/293) PCD patients had perianal lesions. The median follow-up time (range) was 72 months (36 to 108 months). Compared with the patients presented with perianal lesions after CD diagnosis, the onset age of patients with perianal lesions before CD diagnosis was younger ((36.0±12.6) years vs. (24.2±10.2) years), and the rates of male (62.5%, 25/40 vs. 77.9%, 197/253), non-structuring and non-penetrating type (32.5%, 13/40 vs. 56.9%, 144/253) and perianal surgery (55.0%, 22/40 vs.76.7%, 194/253) were high, but low rate of abdominal surgery (37.5%, 15/40 vs. 13.0%, 33/253), and the differences were statistically significant ( t=2.630, χ2=4.442, 8.379, 8.379 and 15.081; all P<0.05). The results of logistic multivariate analysis showed that before CD diagnosis, non-structuring and non-penetrating type was more common than structuring type (odds ratio ( OR)=0.447, 95% confidence interval ( CI) 0.207 to 0.962, P=0.039) and penetrating type ( OR=0.264, 95% CI 0.089 to 0.780, P=0.016). The short disease duration of CD ( OR=0.981, 95% CI 0.968 to 0.995, P=0.008), structuring type ( OR=2.239, 95% CI 1.040 to 4.822, P=0.039) and penetrating type ( OR=3.788, 95% CI 1.281 to 11.198, P=0.016) were the risk factors of perianal lesions after CD diagnosed. The number of PCD patients ( r=0.964, P<0.01) and the proportion of biological agents ( r=0.879, P<0.01) increased with years, while PCD duration ( r=-0.828, P<0.01) and the rate of abdominal surgery significantly decreased with years ( r=-0.882, P<0.01). The proportion of biological agents was negatively correlated with the rate of abdominal surgery ( r=-0.770, P=0.006). Conclusions:The perianal lesions should be closely monitored in adult CD patients with short disease duration, structuring type and penetrating type for early diagnosis and treatment. Biological agents can improve the clinical outcomes of PCD.

Objective To analyze tumor immune microenvironment and related mechanisms in liver cancer.Methods We included 10 cases of hepatocellular carcinoma,hepatitis B patients and healthy volunteers from January 2015 to December 2017 in Shanxi Grand Hospital.We first detected the peripheral and local GM-CSF level in each group,detected myeloid-derived suppressor cells (MDSCs) GM-CSF and pathway-related protein expression.from liver cancer,tumor margin and normal liver tissue through flow cytometry and immunohistochemistry,Finally,we transfected the CCR4-NOT transcriptional complex subunit 7 (CNOT7) recombinant plasmid in the hepatoma cell line,and then detected the related protein expression.Results There was no significant difference for peripheral blood GM-CSF level between liver cancer group,hepatitis group and control group (P＞0.05).The level of local GM-CSF was (32.2±8.9) ng/L,which was higher than that of hepatocellular carcinoma (9.7±2.7) ng/L and normal liver tissue (11.6±2.9) ng/L.The difference was statistically significant (P＜0.05).The proportion of MDSCs at the edge of the tumor was (9.9 ±3.6) ％,which was higher than that of liver cancer (4.0± 1.5) ％ and normal liver tissue (6.3±2.3) ％,and the difference was statistically significant (P＜0.05).Immunohistochemistrydata was consistent with previous data.Compared with normal liver tissue,CNOT7 and STAT3 were highly expressed in liver cancer tissues,while STAT1 was lowly expressed.HepG2 human hepatoma cells were selected for transfection.Compared with the empty plasmid group,CNOT7 expression was decreased in the knocking out group at the same time STAT1 expression was increased,STAT3 and GM-CSF expression was decreased.Conclusion In hepatocellular carcinoma,the secretion of GM-CSF increased and the number of MDSCs increased.Knocking out CNOT7 reduced GM-CSF secretion and activate the JAK/STAT signaling pathway.

Objective: To investigate the safety and efficacy of needle-tract assisted standard percutaneous nephrolithotomy (PCNL) for the treatment of complicated upper urinary tract calculi. Methods: The clinical data of 1 562 patients with complicated upper urinary calculi who received standard PCNL from December 2013 to December 2017 at Department of Urology, the First Affiliated Hospital of Xiamen University were retrospectively analyzed. There were large residual stones in 256 patients through B-ultrasound exploration after standard PCNL, could′t be detected with nephoscope in standard PCNL tracts. 16 F mini PCNL tract were established in 120 cases for treatment of residual stones, while needle-tract were established in order to guide nephroscope to find residual stones in 126 cases. Needle-tract were transferred to 16 F mini PCNL tract for treatment of residual stones in 10 patients if these residual stones could′t be detected through needle-tract. Operation time, change of hemoglobin level after operation, incidence of postoperative complications, time of hospitalization and rate of stone clearance were measured in two groups. The statistical methods used included t test, Wilcoxon rank sum test, and χ² test. Results: There were 1 to 3 mini tracts (M(Q_R): 1(1)) established in the mini tracts group and 1 to 7 needle-tracts (M(Q_R): 3(2)) established in the needle-tract group (Z=-10.57, P=0.000). Compared with mini tract group, the operation time ((62.0±18.0) minutes vs. (84.0±15.5) minutes, t=10.242, P=0.000), hospitalization time ((4.40±0.86) days vs. (5.20±0.81) days, t=7.570, P=0.049), hemoglobin dropped ((1.31±0.47) g/L vs. (2.74±0.63) g/L, t=20.12, P=0.000), and incidence of postoperative complications (7.9% (10/126) vs. 19.2% (23/120), χ²=6.674, P=0.01) of needle-tract group were lower, while postoperative stone clearance rate was higher (89.7% vs. 76.7%, χ²=7.497, P=0.006). No perioperative severe complications such as pleural injury, pneumatothorax, perforation of renal, trauma of abdominal organ occurred in two groups. Conclusion Needle-tract assisted standard PCNL for the treatment of complicated upper urinary calculi can significantly improve stone clearance rate, reduce operation time, decrease risk of kidney and surrounding organs damage.

Objective To investigate the serum γ-glutamyl transferase(γ-GT)level and its clinical significances in hepatitis B virus(HBV)-liver failure(LF)patients.Methods γ-GT levels were detected in 89 LF patients,30 cases with cirrhosis and 30 healthy controls.Difference of serum γ-GT between survival group and death group in LF patients and dynamics of γ-GT after hospitalization were studied. Survival rate between γ-GT increase group and decrease group were compared.The associations of γ-GT with model for end stage live disease(MELD)and prealbumin were calculated.Results At baseline,the γ-GT levels in LF,cirrhosis and healthy control groups were(149.61 ± 69.86),(123.96 ± 59.52)and (48.28 ± 10.25)U/L,respectively,the difference among groups was significant(F= 178.150,P<0.05).The survival group in LF patients showed significant increase of γ-GT one week after hospitalization compared with death group([75.27 ± 10.34]vs[29.47 ± 5.05],t=5.40,P<0.05). The γ-GT increase group showed higher survival rate than γ-GT decrease group[76.19%(48/63)vs 23.08%[6/26],χ2=21.76,P<0.05].Serum γ-GT level in LF patients was positively correlated with both MELD score and prealbumin(r=0.709 and -0.627,respectively,both P<0.05).Conclusions The rise of γ-GT may indicate a better prognosis in LF patients.Serum γ-GT positively correlates with prealbumin and both could reflect the regeneration of hepatocytes.

Objective To compare the long-term outcomes of the retropubic tension-free vaginal tape (TVT) versus the transobturator tension-free vaginal tape (TVT-O) for women with stress urinary incontinence (SUI).Methods From July 2001 to June 2011,data of 120 female patients with SUI were retrospectively reviewed,of which 45 patients received TVT treatment,while 75 patients received TVT-O.The median age in TVT group was 45.1 years (range 35-72 years),and the median age in TVT-O group was 50.5 years (range 39-76 years).We retrospectively analyzed the long-term subjective effect,objective effect and the rate of complications in the two groups.Results Median follow-up period was 121 months (range 72-192 months).The complete satisfaction rate was 89％ (40/45) in TVT group,and 92％(69/75) in TVT-O group,with no statistical difference between the two groups.The negative rate of cough test was 84.4％ (38/45) in TVT group,and 76.0％ (57/75)in TVT-O group,with a statistically significant difference.The rate of urinary tract injury was 8.9％ (4/45) in TVT group,and 4.0％ (3/75) in TVT-O group.The rate of thigh pain was 0 in TVT group,and 6.7％ (3/45) in TVT-O group.The rate of micturition frequency and urinary incomplete emptying after operations was 6.7％ (5/75) in TVT group,and 5.3％ (4/75) in TVT-O group.Conclusions The long-term subjective effect between TVT and TVT-O groups was similar.The objective effect in TVT group was better.There was no statistical difference in complication rate between the two groups,which showed different types of complications in different procedures.