ObjectiveTo introduce visual teaching into the course design of medical humanistic care based on the concept of implementation science， evaluate the teaching implementation effect and feedback， and provide references for optimizing course teaching outcomes and improving students’ humanistic care competence. MethodsA visual teaching program for medical humanistic care was designed， with key steps including clarifying teaching objectives， content， methods， and curriculum assessment. This program was implemented in the medical humanistic care course teaching involving 50 elective students. Multi-dimensional evaluation of teaching effectiveness was conducted through course grades， visual teaching evaluation， and humanistic workshop assessment， combined with inductive content analysis of students’ learning experiences in the workshops. ResultsThe 50 students achieved above-average course grades （89.60±3.41） and demonstrated high satisfaction with the overall course and visual teaching. All the 6 groups obtained relatively high scores in the medical humanistic care workshops. Four themes were extracted， namely， enhancing humanistic care competencies， deepening familial and interpersonal relationships， realizing emotional expression and self-growth， and strengthening integration of humanistic care concepts with practice. ConclusionThe teaching of medical humanistic care course has achieved favorable effects， which contributes to deepening students’ understanding of humanistic care and enhancing their humanistic care competence. Students demonstrate high levels of recognition and satisfaction with the course.

FH-deficient renal cell carcinoma(FH-dRCC) is a rare and highly aggressive subtype of renal cell carcinoma. This tumor is often associated with hereditary leiomyomatosis and renal cell carcinoma(HLRCC) syndrome. Its pathogenesis involves biallelic inactivation of the FH gene, leading to the accumulation of fumarate, which disrupts cellular metabolic balance and DNA repair processes, thereby driving tumorigenesis. This paper reports a patient with FH-dRCC. The patient underwent radical nephrectomy but experienced early postoperative recurrence and liver metastasis. Despite multiple lines of systemic therapy, including targeted and combination immunotherapy, which initially achieved radiographic response, the patient eventually died as the disease progressed with extensive metastases. This case highlights the highly aggressive nature of FH-dRCC, its propensity for early recurrence and metastasis, and the limited duration of response to current systemic therapies. There is a clinical need for enhanced early detection and active exploration of more effective combination treatment strategies.

Objective To investigate the prognostic differences among pure urothelial carcinoma,squamous-differentiated urothelial carcinoma,and pure squamous cell carcinoma,so as to provide reference for postoperative risk stratification.Methods The clinical data of bladder cancer patients who visited the Department of Urology,Peking University First Hospital and underwent radical cystectomy during Jan.2005 and Jun.2024 were retrospectively analyzed.Patients were categorized into the pure urothelial carcinoma group(n=725),squamous-differentiated urothelial carcinoma group(n=189),and pure squamous cell carcinoma group(n=36).General characteristics,surgical approaches,pathological staging,muscle invasion status,and lymph node positivity were compared among the three groups.Kaplan-Meier survival curves were plotted,and prognostic differences among the groups were compared after 1∶1 propensity score matching between each pair.Independent risk factors of prognosis were identified with Cox multivariable regression.Results The pure squamous cell carcinoma group had a higher proportion of female patients(50.00％vs.25.24％vs.22.75％,P=0.002 4).Compared with the pure urothelial carcinoma group,the other two groups demonstrated higher proportions of stage Ⅲ+Ⅳ,higher rates of muscle invasion,and higher lymph node positivity,with the pure squamous cell carcinoma group showing the highest overall staging(69.45％vs.58.20％vs.29.38％,P＜0.000 1).Kaplan-Meier analysis showed that squamous-differentiated urothelial carcinoma group and pure squamous cell carcinoma group had significantly worse survival than the pure urothelial carcinoma group(P＜0.05),while the former two groups exhibited similar outcomes(P=0.85).After propensity score matching,postoperative survival curves among the three groups were not significantly different(all P＞0.05).In multivariable Cox proportional hazards models adjusting for confounders,prognosis was primarily associated with age,muscle invasion,and lymph-node positivity(P＜0.05);pathological subtype was not an independent predictor of postoperative survival.Conclusion In a cohort of non-metastatic patients undergoing radical cystectomy,pure squamous cell carcinoma and squamous-differentiated urothelial carcinoma presented with higher clinical and pathological staging and poorer unadjusted prognosis compared with pure urothelial carcinoma.However,postoperative survival did not differ significantly among the three groups in the same clinicopathological conditions.

Objective To investigate the prognostic differences among pure urothelial carcinoma,squamous-differentiated urothelial carcinoma,and pure squamous cell carcinoma,so as to provide reference for postoperative risk stratification.Methods The clinical data of bladder cancer patients who visited the Department of Urology,Peking University First Hospital and underwent radical cystectomy during Jan.2005 and Jun.2024 were retrospectively analyzed.Patients were categorized into the pure urothelial carcinoma group(n=725),squamous-differentiated urothelial carcinoma group(n=189),and pure squamous cell carcinoma group(n=36).General characteristics,surgical approaches,pathological staging,muscle invasion status,and lymph node positivity were compared among the three groups.Kaplan-Meier survival curves were plotted,and prognostic differences among the groups were compared after 1∶1 propensity score matching between each pair.Independent risk factors of prognosis were identified with Cox multivariable regression.Results The pure squamous cell carcinoma group had a higher proportion of female patients(50.00％vs.25.24％vs.22.75％,P=0.002 4).Compared with the pure urothelial carcinoma group,the other two groups demonstrated higher proportions of stage Ⅲ+Ⅳ,higher rates of muscle invasion,and higher lymph node positivity,with the pure squamous cell carcinoma group showing the highest overall staging(69.45％vs.58.20％vs.29.38％,P＜0.000 1).Kaplan-Meier analysis showed that squamous-differentiated urothelial carcinoma group and pure squamous cell carcinoma group had significantly worse survival than the pure urothelial carcinoma group(P＜0.05),while the former two groups exhibited similar outcomes(P=0.85).After propensity score matching,postoperative survival curves among the three groups were not significantly different(all P＞0.05).In multivariable Cox proportional hazards models adjusting for confounders,prognosis was primarily associated with age,muscle invasion,and lymph-node positivity(P＜0.05);pathological subtype was not an independent predictor of postoperative survival.Conclusion In a cohort of non-metastatic patients undergoing radical cystectomy,pure squamous cell carcinoma and squamous-differentiated urothelial carcinoma presented with higher clinical and pathological staging and poorer unadjusted prognosis compared with pure urothelial carcinoma.However,postoperative survival did not differ significantly among the three groups in the same clinicopathological conditions.

This article reviews the latest research on urothelial carcinoma presented at the 2024 ASCO-GU conference, focusing primarily on the treatment strategies for node-positive muscle-invasive bladder cancer (N + MIBC) and adjuvant therapy post-surgery for muscle-invasive bladder cancer. Patients with N + MIBC are at a higher risk of recurrence and require a comprehensive treatment approach. The combination of neoadjuvant chemotherapy and immunotherapy has demonstrated significant efficacy. Additionally, bladder-sparing treatment and immuno-maintenance therapy show promise in improving disease-free survival. The results from the AMBASSADOR and CheckMate-274 studies indicate that postoperative immuno-adjuvant therapy for high-risk MIBC is beneficial in delaying disease recurrence. These advancements offer new hope for the treatment of patients with high-risk MIBC and may potentially improve patient outcomes.

Muscle-invasive bladder cancer (MIBC) is the predominant type of muscle-invasive urothelial carcinoma (MIUC). MIBC features an unfavorable prognosis with limited treatment approaches. The backbone of treatment strategy was neoadjuvant chemotherapy followed by radical cystectomy before 2021. Immunotherapy represented by nivolumab has gained breakthrough results in adjuvant setting, demonstrating significant improvement in disease free survival in high-risk MIUC population, and become a standard of care for MIUC adjuvant therapy since 2021. Immunotherapy has both efficacy and safety advantages compared to adjuvant chemotherapy. Predictors for adjuvant therapy response in MIUC have yet not been identified. The most evaluated predictive biomarkers to date for immune checkpoint inhibitor treatment response are programmed death ligand 1 (PD-L1) expression and circulating tumour DNA (ctDNA), etc. Further research is crucial to assess the value of the biomarkers. Studies of perioperative immunotherapy combined with chemotherapy or antibody-drug conjugate are ongoing. Combined immunotherapy as part of bladder-sparing treatment regimen for MIUC is limited to small scale studies and has shown promising early outcomes. Further phase 3 clinical trials are underway to add mature data to bladder-sparing strategies incorporating immune checkpoint inhibitors in adjuvant setting.

Muscle-invasive bladder cancer (MIBC) is the predominant type of muscle-invasive urothelial carcinoma (MIUC). MIBC features an unfavorable prognosis with limited treatment approaches. The backbone of treatment strategy was neoadjuvant chemotherapy followed by radical cystectomy before 2021. Immunotherapy represented by nivolumab has gained breakthrough results in adjuvant setting, demonstrating significant improvement in disease free survival in high-risk MIUC population, and become a standard of care for MIUC adjuvant therapy since 2021. Immunotherapy has both efficacy and safety advantages compared to adjuvant chemotherapy. Predictors for adjuvant therapy response in MIUC have yet not been identified. The most evaluated predictive biomarkers to date for immune checkpoint inhibitor treatment response are programmed death ligand 1 (PD-L1) expression and circulating tumour DNA (ctDNA), etc. Further research is crucial to assess the value of the biomarkers. Studies of perioperative immunotherapy combined with chemotherapy or antibody-drug conjugate are ongoing. Combined immunotherapy as part of bladder-sparing treatment regimen for MIUC is limited to small scale studies and has shown promising early outcomes. Further phase 3 clinical trials are underway to add mature data to bladder-sparing strategies incorporating immune checkpoint inhibitors in adjuvant setting.

Silver nanoparticles (AgNPs) is known as one of the most valuable metal nanoparticles in antibacterial and anticancer application. AgNPs-resistant bacteria has been documented, but it is unclear whether cancer cells can also escape the anti-cancer effect of AgNPs. In this study, we aimed to investigate this phenomenon and its underlying mechanism. The antibacterial activity and cytotoxicity of AgNPs were measured in the presence of HeLa cell metabolites. The status of AgNPs in the system associated with metabolites were characterized by UV-Vis, Zetasizer Nano ZS, and transmission electron microscopy. Non-targeted metabolomics was used to reveal the metabolites components that bind with AgNPs. HeLa cells were injected intraperitoneally to establish the tumor-bearing mice model, and the stability of AgNPs in mice serum was analyzed. The results manifested that HeLa cell metabolites inhibited the anticancer and antibacterial effects of AgNPs in a dose-dependent manner by causing AgNPs aggregation. Effective metabolites that inhibited the biological activity of AgNPs were stable in 100 ℃, insoluble in chloroform, containing sulfur elements, and had a molecular weight less than 1 kDa in molecular weight. There were 115 compounds bound with AgNPs. In vitro experiments showed that AgNPs aggregation occurred only when the concentration of α-ketoglutarate (AKG) and glutathione (GSH) together reached a certain threshold. Interestingly, the concentration of AKG and GSH in HeLa cellular metabolites was 10 and 6 times higher than that in normal cervical epithelial cells, respectively, which explained why the threshold was reached. Furthermore, the stability of AgNPs in the serum of tumor-bearing mice decreased by 20% (P < 0.05) compared with the healthy mice. In conclusion, our study demonstrates that HeLa cells escaped the anti-cancer effect of AgNPs through the synergistic effect of AKG and GSH, suggesting the need to develop strategies to overcome this limitation.
Humans ; Animals ; Mice ; HeLa Cells ; Silver/pharmacology* ; Ketoglutaric Acids/pharmacology* ; Metal Nanoparticles ; Anti-Bacterial Agents/pharmacology* ; Glutathione ; Microbial Sensitivity Tests

Objective:To evaluate risk factors for local recurrence and prognosis in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy combined with lymph node dissection (LND).Methods:The data of 237 patients who were diagnosed with UTUC in Peking University First Hospital and received radical nephroureterectomy combined with LND during January 2010 and March 2022 were retrospectively reviewed. Clinicopathologic characteristics and oncological outcomes were compared according to lymph node metastasis. There were 122 males and 115 females. The tumors of 122 cases were located on the left, while 115 cases were on the right. The tumors of 102 cases were in the renal pelvic, 124 cases in the ureter and 11 cases in both sites. The mean age was (65.52±10.14) years old. The overall survival (OS), cancer-specific survival (CSS), local recurrence-free survival (LRFS) of all patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between two groups were analyzed by log-rank test. Univariate and multivariate Cox proportional hazards regressions were performed to identify the independent risk factors for CSS and LRFS.Results:There were 122 males and 115 females. According to the lymph node metastasis, the patients were divided into lymph node negative group ( n=180, 75.9%) and lymph node positive group ( n=57, 24.1%). Lymph node positive group had a higher percentage in renal tumor [57.9%(33/57) vs. 38.1% (69/180)], stage T 3-4 [84.2%(48/57) vs. 32.8%(59/180)], G 3 [91.2%(52/57) vs. 55.6%(100/180)], glandular differentiation [17.5%(10/57) vs. 4.4%(8/180)], sarcomatoid differentiation [22.8%(13/57) vs. 9.4%(17/180)], necrosis [47.4%(27/57) vs. 16.1%(29/180)], lymphovascular invasion [40.4%(23/57) vs. 12.2%(22/180)] and the number of lymph node dissection [ 4(1, 10) vs. 2(1, 5)]. There were significant differences between the two groups ( P<0.05). Of 237 patients, 42 lost of follow up. The median follow-up time was 46(22, 79) months. Among the 195 patients, 52 patients died, and 42 died due to the tumor. Of all patients, 58(29.7%) had local recurrence, 34 had local recurrence alone, and 24 had concurrent distant metastasis. The 5-year OS and CSS were 67.4% and 71.3%, respectively. The 5-year OS and CSS were 70.5% and 75.1% respectively in the lymph node negative group, 57.5% and 59.4% respectively in the lymph node positive group ( P < 0.05). The 3-year LRFS was 68.0% for all the patients. The 3-year LRFS was 75.6% in the lymph node negative group and 44.5% in the lymph node positive group ( P<0.05). Multivariate analysis showed that tumor stage T 3-4( HR =3.924, 95% CI 2.045-7.529, P<0.001) and G 3( HR=2.871, 95% CI 1.193-6.909, P =0.019) were independent risk factors for LRFS. Multivariate analysis showed that age ≥70 years ( HR = 3.578, 95% CI 1.917-6.678, P<0.001) and pathological stage T 3-4 ( HR =2.366, 95% CI 1.278-4.381, P =0.006) were independent risk factors for CSS. Multivariate analysis showed that age ≥70 years ( HR = 3.874, 95% CI 2.190-6.853, P<0.001) and pathological stage T 3-4 ( HR = 2.757, 95% CI 1.565-4.857, P<0.001) were independent risk factors for OS. Conclusions:Patients with high T stage, high grade, as well as glandular differentiation, sarcomatoid differentiation, necrosis, lymphovascular invasion are more likely to have positive lymph node detection. Age ≥70 years and stage T 3-4 were independent risk factors for CSS and OS. Stage T 3-4 and G 3were independent risk factors for LRFS.

Objective:To study the value of urine-based multi-dimensional bioinformatics evaluation model (utLIFE model) in early diagnosis and postoperative monitoring of upper urinary tract urothelial carcinoma (UTUC).Methods:Morning urine samples of patients clinically diagnosed with UTUC without bladder cancer from Peking University First Hospital from August 2022 to October 2022 were collected. Urine samples were collected before and after surgery, and DNA was extracted for gene sequencing. The utLIFE model previously constructed by our center was used to calculate the score, based on 155 gene mutation sites and copy number variation, and the score ≥60 was defined as utLIFE positive. The sensitivity of utLIFE model in diagnosis of UTUC was analyzed with postoperative pathology as the gold standard. The utLIFE scores before and after operation were also compared.Results:A total of 53 patients were included in this study, all of whom were confirmed as UTUC by postoperative pathology. The median age of patients was 66 (59, 72) years. Twenty-four cases (45.3%) of UTUC tumors were located in the renal pelvis, 26 cases (49.1%) were located in the ureter, and 2 cases (5.7%)involved both ureter and renal pelvis. There were 27 patients (50.9%) at T 1stage and 26 patients (49.1%) at ≥T 2 stage. Preoperative utLIFE score of 53 patients was 79 (70, 84). The sensitivity of preoperative utLIFE diagnosis of UTUC was 96.2% (51/53). utLIFE showed similar high sensitivity in T 1 stage and ≥T 2 stage [100.0% (27/27) vs. 92.3% (24/26), P=0.236], in N 0 and ≥N 1 stage [ 95.0% (38/40) vs. 100.0% (5/5), P=1.000]. In addition, the sensitivity of preoperative utLIFE was higher than that of urine cytology [ 95.2% (20/21) vs. 23.8% (5/21). P<0.001], fluorescence in situ hybridization (FISH) [ 92.6% (25/27) vs. 55.5% (15/27), P=0.004] and ureteroscopy [ 86.7% (13/15) vs. 60.0% (9/15), P=1.000]. A total of 45 patients postoperative utLIFE samples were collected, and the postoperative utLIFE score was significantly lower than that of preoperative [ 36 (18, 61) vs. 79 (70, 84), P<0.001]. Conclusions:utLIFE, as a non-invasive urine DNA bioinformatics assessment model, is significantly superior to cytology and FISH in early detection and has high sensitivity in diagnosis of UTUC, and can reflect perioperative minimal residual disease levels.