Miao Wang

Antibody-drug conjugates (ADCs) have made important advances in the treatment of bladder cancer (BC) in recent years and have demonstrated significant clinical benefit in locally advanced or metastatic urothelial carcinoma (UC). However, the emergence of resistance remains a key factor limiting the durability of their therapeutic efficacy. Current evidence indicates that resistance to ADCs in BC is a complex process driven by multiple tumor-intrinsic and tumor-extrinsic factors. This review systematically summarizes the major mechanisms underlying ADC resistance in BC and outlines potential strategies to overcome it, including the development of next-generation ADCs, combination therapies, and predictive biomarkers. A deeper understanding of BC-specific mechanisms of ADC resistance will help promote the development of more precise and individualized ADC-based treatment strategies.

Women presenting with urinary tract symptoms such as bladder stones are often presumed to have primary urological disease. However, urogynecologic conditions—including vesicovaginal fistula (VVF) and retained vaginal foreign bodies—can rarely manifest with predominant urological symptoms, leading to diagnostic delay. A 20-year-old female presented with persistent lower urinary tract discomfort and urinary leakage for 2 years. She denied abdominal pain, distension, or menstrual irregularities. No psychiatric or surgical history was reported, and renal function was within normal limits [serum creatinine 73.9 µmol/L; estimated glomerular filtration rate (eGFR) 100.96 mL/min/1.73 m²]. Contrast-enhanced computed tomography (CT) suggested mildly reduced right renal excretory function, raising concern for possible early functional compromise in the setting of chronic hydronephrosis. Imaging further revealed a bladder stone associated with a retained vaginal foreign body and a 2-cm vesicovaginal fistulous tract, complicated by bilateral upper urinary tract dilatation/giant ureters. The patient underwent a combined transabdominal–transvaginal procedure for complete removal of the stone and foreign body, multilayer fistula repair, and bilateral double-J ureteral stenting. The ureteral stents were removed 1 month postoperatively. CT urography performed 5 months after stent removal demonstrated marked improvement of upper urinary tract dilatation with no evidence of contrast extravasation into the vagina. This case underscores that an apparently straightforward urological presentation may conceal complex urogynecologic pathology. Early cross-disciplinary assessment between urology and gynecology, supported by targeted imaging and functional evaluation, is essential for timely diagnosis and comprehensive management.

Lymphangioleiomyomatosis (LAM) is an uncommon systemic disease that primarily affects women during their reproductive years and is often linked with renal angiomyolipoma (AML). In this report, we describe a case involving a 30-year-old female patient who presented with a large AML in her right kidney. Imaging revealed diffuse pulmonary cysts, raising clinical suspicion of LAM. The procedure was initially planned as a minimally invasive partial nephrectomy performed with robotic assistance but was converted to open radical nephrectomy due to excessive intraoperative bleeding. Histopathological analysis confirmed epithelioid AML, and genetic testing revealed a somatic TSC2 mutation, further supporting the diagnosis of sporadic LAM. This case highlights the need to consider LAM in young women with renal AML and emphasizes the value of multidisciplinary management in addressing such complex clinical scenarios.

Kidney stone disease is a multifactorial disease with increasing incidence worldwide. Trans-ancestry GWAS has become a popular strategy to dissect genetic structure of complex traits. Here, we conduct a large trans-ancestry GWAS meta-analysis on kidney stone disease with 31,715 cases and 943,655 controls in European and East Asian populations. We identify 59 kidney stone disease susceptibility loci, including 13 novel loci and show similar effects across populations. Using fine-mapping, we detect 1612 variants at these loci, and pinpoint 25 causal signals with a posterior inclusion probability >0.5 among them. At a novel locus, we pinpoint TRIOBP gene and discuss its potential link to kidney stone disease. We show that a cross-population polygenic risk score, PRS-CSx_EAS&EUR, exhibits superior predictive performance for kidney stone disease than other polygenic risk scores constructed in our study. Relative to individuals in the third quintile of PRS-CSx_EAS&EUR, those in the lowest and highest quintiles exhibit distinct kidney stone disease risks with odds ratios of 0.57 (0.51–0.63) and 1.83 (1.68–1.98), respectively. Our results suggest that kidney stone disease patients with higher polygenic risk scores are younger at onset. In summary, our study advances the understanding of kidney stone disease genetic architecture and improves its genetic predictability.

Background: Zinner syndrome is a rare congenital malformation of the male genitourinary system, characterized by a triad: seminal vesicle cyst, unilateral renal agenesis, and ipsilateral ejaculatory duct obstruction. The etiology of this uncommon disease remains largely elusive; however, genetic mutations may contribute to its development. In this report, we present a case of symptomatic Zinner syndrome that was surgically treated, alongside an investigation into the potential genetic basis of the syndrome via whole exome sequencing. Case presentation: We report the case of an 18-year-old male presenting with urinary pain and was diagnosed with right renal agenesis and a left seminal vesicle cyst following comprehensive imaging. The patient also experienced perineal pain and urgency, without symptoms of frequent urination, dysuria, or hematuria, and no familial history of genitourinary anomalies was documented. He successfully underwent laparoscopic resection of a pelvic mass, with pathological examination confirming a seminal vesicle cyst. Postoperative recovery was uneventful. Whole exome sequencing of blood and tissue samples highlighted myeloma overexpressed gene (MYEOV), B melanoma antigen family member (BAGE), and N-acetylated-alpha-linked acidic dipeptidase 2 (NAALAD2) as potential mutated genes related to Zinner syndrome. Additionally, two predisposing genetic variants were identified. Conclusions: Zinner syndrome is a rare condition commonly diagnosed via various imaging modalities. Surgical resection remains the most effective treatment for symptomatic cases. Gene sequencing provides valuable insights into the genetic etiology of Zinner syndrome, enhancing our understanding and potentially guiding future diagnostic approaches.

The adverse effects of early-life tobacco smoke exposure on chronic kidney disease (CKD) risk remain unclear. This study aimed to investigate the associations of early-life tobacco smoke exposure with CKD incidence in adulthood, and further explore the modification effects of physical activity (PA). A total of 352,883 participants were included from the UK Biobank. The information on early-life tobacco smoke exposure was assessed by employing in utero tobacco smoke exposure and age of smoking initiation. Weekly moderate-to-vigorous physical activity (MVPA) was calculated for each individual. Cox proportional hazard regression was fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI) of CKD risk, and to investigate the modification effects of MVPA. CKD incidence significantly increased in participants with in utero tobacco smoke exposure (HR: 1.08, 95% CI: 1.04, 1.12). Compared with never-smokers, we found a monotonic increase in the risk of CKD with smoking initiation across adulthood (HR: 1.21, 95% CI: 1.16, 1.27), adolescence (HR: 1.29, 95% CI: 1.24, 1.35), and childhood (HR: 1.34, 95% CI: 1.25, 1.43) (P trend < 0.001). Additionally, we identified joint cumulative effects of MVPA and early-life tobacco smoke exposure on incident CKD. Compared with never-smokers with recommended MVPA, prenatal or childhood tobacco smokers without recommended MVPA had the highest CKD risk, and the HRs (95% CIs) were 1.17 (1.10, 1.24) and 1.51 (1.36, 1.68), respectively. Early-life tobacco smoke exposure may contribute to CKD incidence in adulthood, and the observed associations could be modified by MVPA. These findings provide important information on CKD prevention in the participant’s early life while urging a more rapid and powerful need for tobacco control among pregnant couples, children, and adolescents.

Objective This study aimed to investigate the role of the long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in the epithelial-mesenchymal transition (EMT) of bladder cancer cells and the potential mechanisms. Methods Cell invasion, migration, and wound healing assays were conducted to assess the effects of MEG3 on the invasive and migratory capabilities of bladder cancer cells. The expression levels of E-cadherin were measured using Western blotting, RT-qPCR, and dual luciferase reporter assays. RNA immunoprecipitation and pull-down assays were performed to investigate the interactions between MEG3 and its downstream targets. Results MEG3 suppressed the invasion and migration of bladder cancer cells and modulated the transcription of E-cadherin. The binding of MEG3 to the zinc finger region of the transcription factor Snail prevented its ability to transcriptionally repress E-cadherin. Additionally, MEG3 suppressed the phosphorylation of extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and P38, thereby decreasing the expression of Snail and stimulating the expression of E-cadherin. Conclusion MEG3 plays a vital role in suppressing the EMT in bladder cancer cells, indicating its potential as a promising therapeutic target for the treatment of bladder cancer.

Background: A series of novel inflammation-related indexes has been confirmed to be efficient indicators of human immune and inflammatory status, with great potential as predictors for a variety of diseases. However, the association between inflammation-related indexes and sex hormones in the general population remained uncertain.Methods: We incorporated data from the NHANES 2013-2016 survey of American adults. On the basis of distribution and comparison analysis, we chose to undertake separate analyses of men and women (including premenopausal and postmenopausal groups). Multivariable weighted linear regression models, eXtreme Gradient Boosting (XGBoost) models, generalized linear analysis, stratified models, logistic regression models and sensitivity analysis were utilized to assess the relationships between inflammation-related indexes and sex hormones.Results: Total 9372 participants out of 20146 were fitted into our research. We conducted separate gender analysis due to different distribution. Multivariable weighted linear regression indicated every component of the inflammation-related index was negatively correlated with at least one component of the male hormone indexes. However, SII, NLR, PPN, and NC were associated positively with female estradiol. XGBoost identify SII, PLR and NLR were the critical indexes on sex hormones. Inflammation-related indexes was associated with Testosterone deficiency in male and postmenstrual group and associated with Excessive Estradiol in premenstrual group. Finally, the subgroup analysis revealed that the association between sex hormones and inflammatory indicators was prominent in American adults over the age of 60 or those with BMI (>28 kg/m²).Conclusion: In all, inflammation-related indexes act as independent risks associated with sex hormone alterations and metabolic disorder in both genders. Using multiple models, we revealed the relative importance of inflammation-related indexes. Subgroup analysis also identified the high-risk population. More prospective and experimental research should be conducted to validate the results.

We carried out whole transcriptome sequencing (WTS) on the tumor and the matching adjacent normal tissues from five patients having Xp11 translocation renal cell carcinoma (RCC). This was performed in terms of obtaining more understanding of the genomic panorama and molecular basis of this cancer. To examine gene-regulatory networks in XP11 translocation RCC, variance expression analysis was carried out, followed by functional enrichment analysis. Gene Expression Omnibus (GEO) of Xp11 translocation RCC data was used to validate the results. As per inclusion criteria, a total of 1886 differentially expressed mRNAs (DEmRNAs), 56 differentially expressed miRNAs (DEmiRNAs), 223 differentially expressed lncRNAs (DElncRNAs), and 1764 differentially expressed circRNAs (DEcircRNAs) were found. KEGG enrichment study of DEmiRNA, DElncRNA, and DEcircRNA target genes identified the function of protein processing in the endoplasmic reticulum, lysosome, and neutrophil-mediated immunity. Three subnetwork modules integrated from the PPI network also revealed the genes involved in protein processing in the endoplasmic reticulum, lysosome, and protein degradation processes, which may regulate the Xp11 translocation RCC process. The ceRNA complex network was created by Cytoscape, which included three upregulated circRNAs, five upregulated lncRNAs, 24 upregulated mRNAs, and two downregulated miRNAs (hsa-let-7d-5p and hsa-miR-433-3p). The genes as a prominent component of the complex ceRNA network may be key factors in the pathogenesis of Xp11 translocation RCC. Our findings clarified the genomic and transcriptional complexity of Xp11 translocation RCC while also pointing to possible new targets for Xp11 translocation RCC characterization.