Urothelial carcinoma (UC), including bladder urothelial carcinoma and upper tract urothelial carcinoma (UTUC), is the most common malignant tumor in the urinary system. Traditional cell line models fall short in simulating its tumor microenvironment and in vivo behavior. Patient-derived organoid (PDO) models offer a new way to overcome these shortcomings. This paper reviews the construction techniques of PDO models in UC, their biological simulation capabilities, and their applications in preclinical research. It also analyzes the technical limitations of these models. PDO models can retain the histological, genomic, and transcriptomic features of the parent tumor and accurately simulate the tumor microenvironment and biological behavior. They have been widely used in bladder cancer research, providing a precise platform for drug screening, personalized treatment, and immunotherapy evaluation. However, their use in UTUC research is still in its infancy. In the future, through technological optimization, PDO models are expected to enhance their value in UC research, advancing precision medicine research and clinical translation.

Objective:To investigate the clinical outcomes of nephron-sparing surgery (NSS) for tuberous sclerosis complex(TSC) -associated renal angiomyolipoma (RAML). Methods:This retrospective case-series study analyzed the clinical data of 15 TSC-RAML patients who underwent NSS at the Department of Urology, Peking Union Medical College Hospital between April 2013 and July 2024. The cohort included 4 males and 11 females. The age at TSC diagnosis was (28.5±14.5) years (range: 5 to 62 years), and the age at first surgery was (33.3±10.8) years (range: 18 to 62 years). The maximum tumor diameter( M(IQR)) was 6.4(7.9)cm (range: 3.5 to 31.5 cm). Patient baseline characteristics, surgical approach, TSC-RAML staging, imaging findings, and laboratory data were collected. Relationships between variables were analyzed using Generalized Estimating Equations with post-hoc tests. Results:A total of 18 surgical procedures were performed on the 15 patients. These included 7 open surgeries, 9 laparoscopic surgeries, and 2 laparoscopic procedures converted to open surgery. The mean preoperative serum creatinine level was (70.2±14.2) μmol/L (range: 50 to 101 μmol/L), which increased to (99.2±29.8) μmol/L (range: 47 to 171 μmol/L) on postoperative day 1. However, at one year postoperatively, serum creatinine was (76.8±13.5)μmol/L (range: 55 to 106 μmol/L),showed no significant difference from preoperative levels ( P>0.05). At the 6-month postoperative follow-up, the Utrecht Interventional Classification stage for all treated tumors had decreased to grade 1 or 2. At the 12-month follow-up (available for 13 patients), 11 patients showed no disease progression. Conclusions:NSS is a viable treatment option for rigorously selected patients with high-stage TSC-RAML. Although NSS causes transient renal function impairment, it provides effective tumor burden control. In stringently selected patients with high-stage disease and under long-term follow-up, NSS is associated with limited long-term renal impairment.

The sirtuin protein family represents a highly conserved group of NAD+-dependent protein deacetylases,comprising seven isoforms in mammals,each with distinct subcellular localizations and biological functions.They play important roles in regulating metabolic reprogramming,cell death,and the development of tumor phenotypes.Consequently,modulating deacetylase activity is regarded as a promising therapeutic option in pathology.This article focuses on elucidating the roles and molecular mechanisms of sirtuins in tumor evolution,as well as the application of sirtuin activators and inhibitors in oncology,to guide targeted therapy and drug development for related malignancies.

Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

Objective:To explore the efficacy and safety of mitotane in adrenal cortical carcinoma (ACC) at high risk of recurrence.Methods:A prospective observational study was designed from September 2022 to November 2023. ACC patients undergoing surgery with high recurrence risk (positive margin or Ki-67 index >10% or capsule rupture or large size or high-grade ACC) in Peking Union Medical College Hospital were enrolled in this study. All patients started mitotane treatment within 3 months after surgery, with a dose of 1.5 g/d, increased by 0.5 g per week. Once the dose reached 3 g/day, adjustments were made based on blood concentration levels. All patients received mitotane therapy for at least 1 year, and CT was performed every 12 weeks to evaluate the efficacy. The primary endpoint was 1-year progression-free survival (PFS) and safety. The efficacy was analyzed by Kaplan-Meier method for survival, and the occurrence of treatment-related adverse events was summarized.Results:A total of 12 ACC patients at high risk of recurrence were screened, comprising 6 males and 6 females. Tumors were located on the left side in 8 patients, on the right in 3, and bilaterally in 1. Five patients were classified as ENSAT stageⅡ, while 7 were classified as ENSAT stage Ⅲ. The maximum diameter of tumor was (9.07 ± 2.86) cm; the median age at diagnosis was 48 (35, 51) years, and the median Ki-67 index was (28.9 ± 16.1)%. The median time from surgery to initiation of mitotane therapy was 31 (23.0, 43.2) days, and 9 patients had blood drug concentrations of 14-20 mg/L. The median follow-up time was 16.7 (12.4, 25.2) months. At 1 year after mitotane therapy, 10 (83.8%) patients were still in disease-free survival state, with a median mitotane PFS of 27.6 months (95% CI 16.4-not reached). All ACC patients experienced 1-2 grade adverse events after taking mitotane. One patient (8.3%) experienced grade 3 adverse event, including the increasing of alanine aminotransferase and aspartate aminotransferase, as well as anorexia. No grade 4-5 adverse events occurred. The most common adverse events were gastrointestinal symptoms (10 cases), including nausea, vomiting, anorexia, and diarrhea, followed by liver function damage(9 cases) and neurotoxicity(4 cases). Conclusions:Mitotane has shown the prospect of improving the prognosis of ACC patients at high risk of recurrence after surgery. Because of its serious toxic and side effects, it is necessary to monitor its blood concentration to adjust the dosage, and take measures for adverse reactions to ensure the safety of patients.

Adrenocortical carcinoma（ACC）is a rare and highly aggressive malignant tumor. Currently，mitotane is the first-line treatment. However，reports on neoadjuvant therapy for ACC using mitotane combined with immune checkpoint inhibitors remain scarce. This article reports a case of ACC. The patient was asymptomatic，and a right adrenal mass was detected during examination. Diagnostic imaging and endocrine evaluation confirmed the diagnosis of ACC. Due to the large tumor size，radical resection was initially considered unfeasible. After 7 months of mitotane therapy and two courses of tislelizumab，significant tumor shrinkage was achieved，allowing for successful open resection of the large right adrenal tumor combined with right nephrectomy. Postoperative histopathological examination confirmed the diagnosis of ACC. During the 3-month postoperative follow-up，no evidence of recurrence or metastasis was observed.

Objective:To investigate the efficacy of unilateral adrenalectomy combined with contralateral partial adrenalectomy in patients with bilateral macronodular adrenal cortical disease（BmacAD）.Methods:Retrospective analysis was performed on the clinical data of 41 patients with bilateral macronodular adrenal disease（BmacAD）who underwent unilateral total adrenalectomy plus contralateral partial adrenalectomy at Peking Union Medical College Hospital，Chinese Academy of Medical Sciences，between January 1990 and December 2018. The cohort comprised 27 men（65.9%）and 14 women（34.1%），with a mean age of（48.5 ± 9.3）years. The median disease duration was 60（25，108）months . Twenty-six patients（63.4%）presented with clinical features of Cushing’s syndrome（CS），while 15 patients（36.6%）did not exhibit typical CS symptoms. Endocrine evaluation revealed a median 24-hour urinary free cortisol（24h-UFC）level of 429.1（255.3，799.2）μg/24h. Plasma adrenocorticotropic hormone（ACTH）was normal in 5 patients（12.2%）and suppressed in 36 patients（87.8%）. Computed tomography（CT）imaging demonstrated typical multinodular involvement of both adrenal glands in all patients. The mean volume of the left adrenal gland was（57.4 ± 31.8）ml，the mean volume of the right adrenal gland was（48.8 ± 18.0）ml，and the mean total volume was（106.2 ± 42.1）ml. The mean maximum nodule diameter was（2.4 ± 1.0）cm. All 41 patients underwent unilateral total adrenalectomy plus contralateral partial adrenalectomy. Postoperatively，patients were followed up every 3 to 6 months to monitor symptoms and hormonal changes. Residual adrenalectomy was performed if symptoms or hormone levels did not improve or recurred.Results:Of the 41 patients，2 underwent simultaneous unilateral total adrenalectomy plus contralateral partial adrenalectomy，while 39 underwent staged procedures. The median follow-up was 56 months（range 2 to 199 months）. During the follow-up period，82.9%（34/41）of patients achieved normalization of clinical symptoms and biochemical markers postoperatively. The median time to improvement of CS symptoms was 19 months. The median 24h-UFC level at 1 week postoperatively was 385.48（219.95，525.04）μg/24h，decreasing to 56.96（37.38，88.70）μg/24h at 3 months postoperatively. All 41 patients received routine glucocorticoid supplementation postoperatively，with gradual tapering until discontinuation. The median duration of hormone replacement was 29 months（3，72）months. Among the 34 patients who did not experience recurrence，30（88.2%）were eventually able to discontinue hormone replacement，with a median duration of supplementation of 24（3，36）months，while 4（11.8%）required long-term hormone replacement. The final outcome showed that 73.2%（30/41）of patients achieved control of CS symptoms with preservation of normal adrenal function following unilateral total adrenalectomy plus contralateral partial adrenalectomy. Seven patients（17.1%）required completion adrenalectomy for residual disease. There were no statistically significant differences（ P > 0.05）in preoperative clinical symptoms，hormone levels，adrenal gland volume，or maximum nodule diameter between patients who experienced recurrence after unilateral total adrenalectomy plus contralateral partial adrenalectomy and those who did not. Conclusions:Unilateral adrenalectomy with contralateral partial adrenalectomy represents a feasible treatment strategy for BmacAD，but requires careful patient selection. This approach may offer a balance between therapeutic efficacy and preservation of adrenal function，providing a novel perspective for clinical decision-making.

Objective:To explore the differences in clinicopathological features and prognosis between conventional adrenocortical carcinoma（ACC）and oncocytic ACC.Methods:The clinical and pathological data of patients with conventional ACC and oncocytic ACC who were admitted to Peking Union Medical College Hospital from March 2012 to Fabruary 2025 were retrospectively analyzed. Differences in clinical and pathological characteristics between the two groups were compared. Survival curves were plotted using the Kaplan-Meier method，and differences in survival rates were compared using the log-rank test.Results:The conventional ACC group comprised 137 cases，with a mean age of（47.5 ± 12.6）years and 37.2%（51/137）being male. The oncocytic ACC group included 22 cases，with a mean age of（49.1 ± 15.3）years and 59.1%（13/22）being male. No statistically significant differences were observed in age or gender distribution between the two groups（ P > 0.05）. The conventional ACC group exhibited a significantly higher prevalence of classic Cushing’s syndrome symptoms compared to the oncocytic ACC group［35.2%（45/128）vs. 5.3%（1/19）； χ2 = 6.876， P < 0.01］. Additionally，the proportion of hypertension was higher in the conventional ACC group［49.2%（65/132）vs. 22.2%（4/18）； χ2 = 5.319， P < 0.05］，whereas the prevalence of adrenal sex characteristics was lower［22.0%（28/127）vs. 63.2%（12/19）； χ2 = 14.043， P < 0.01］. The Ki-67 proliferation index was significantly higher in conventional ACC patients［20%（10%，40%）vs. 12%（9%，20%）； Z = -2.113， P < 0.05］. Furthermore，the conventional ACC group demonstrated a lower 5-year overall survival rate than the oncocytic ACC group（44.5% vs. 67.3%， P < 0.05）. Conclusions:Conventional ACC patients have a higher proportion of Cushing’s symptoms and hypertension，and oncocytic ACC patients have a higher proportion of adrenal sexual characteristics abnormalities. The prognosis of oncocytic ACC is better than that of conventional ACC.

This article focuses on the deepening and innovation of grassroots party building work in public hospitals,tak-ing Sijing Hospital in Songjiang District,Shanghai as a case study.It explores how public hospitals can improve service quality and promote high-quality development through party building work in the new era.By analyzing the main problems faced by party building work,this article proposes practical paths for innovative party building work,including establishing a party building grid management organizational framework,formulating and improving party building management standards and systems,standardi-zing party building project processes,and strengthening party building assessment and supervision.Through the deepening and innovation of party building work,the integration of party building work and hospital business is achieved,thereby enhancing the overall service capacity and management level of the hospital,cultivating high-quality medical and health personnel,and provi-ding solid political guarantees and organizational support for the sustainable development of public hospitals.