The m6A Reader YTHDF2 Promotes Bladder Cancer Progression by Suppressing RIG-I-Mediated Immune Response.

N6-Methyladenosine (m6A) is the most prevalent internal modification of mammalian mRNAs. Recent studies have shown that m6A methyltransferases METTL3 and METTL14 play important roles in urothelial bladder carcinoma (BLCA). To provide a more comprehensive understanding of the m6A regulatory landscape in bladder cancer, we investigated the role of YTHDF2, a crucial m6A reader, in BLCA. YTHDF2 was frequently upregulated at both the RNA and protein level in BLCA. Functionally, YTHDF2 promoted the proliferation and tumor growth of BLCA cells in vitro and in vivo, respectively. Integrative RNA sequencing and m6A sequencing analyses identified RIG-I as a downstream target of YTHDF2. Mechanistically, YTHDF2 bound to the coding sequence of DDX58 mRNA, which encodes RIG-I, and mediated its degradation in an m6A-dependent manner. Knockdown of RIG-I inhibited apoptosis and promoted the proliferation of BLCA cells. Depleting RIG-I was also able to reverse the effects of YTHDF2 deficiency. YTHDF2-deficient BLCA cells implanted orthotopically in recipient mice activated an innate immune response and promoted recruitment of CD8+ T lymphocytes into the tumor bed and the urothelium. Moreover, YTHDF2 deficiency enhanced the efficacy of Bacillus Calmette-Guérin immunotherapy treatment. This study reveals that YTHDF2 acts as an oncogene in BLCA. YTHDF2 inhibits RIG-I to facilitate immune evasion, supporting testing YTHDF2 inhibition in combination with immunotherapy. SIGNIFICANCE: YTHDF2 regulates RIG-I-mediated innate immune signaling to support bladder cancer progression, highlighting the functional importance of m6A modifications in bladder cancer and uncovering therapeutic opportunities to improve patient outcomes.

Primary Langerhans cell sarcoma in the urinary bladder: Case report and literature review.

Langerhans cell sarcoma (LCS) is a rare malignancy of dendritic cells and usually results in a poor oncological outcome. Thus, LCS is usually given a positive administration. Herein, we presented the first case of primary LCS in the urinary bladder staged T1N0M0 and treated by TURBT and short-term local chemotherapy. Our experience in this unique case may suggest that LCS in the urinary bladder with a non-muscle-invasive stage may be managed according to the treatment model of non-muscle-invasive urothelial carcinoma of the urinary bladder.

AIM2 inflammasome activation benefits the therapeutic effect of BCG in bladder carcinoma.

A large proportion of bladder cancer (BLCA) patients suffer from malignant progression to life-threatening muscle-invasive bladder cancer (MIBC). Inflammation is a critical event in cancer development, but little is known about the role of inflammation in BLCA. In this study, the expression of the innate immune sensor AIM2 is much lower in high-grade BLCA and positively correlates with the survival rates of the BLCA patients. A novel AIM2 overexpressed BLCA model is proposed to investigate the impact of AIM2 on BLCA development. Mice inoculated with AIM2-overexpressed cells show tumor growth delay and prolonged survival compared to the control group. Meanwhile, CD11b+ cells significantly infiltrate AIM2-overexpressed tumors, and AIM2-overexpression in 5637 cells enhanced the inflammasome activation. In addition, oligodeoxynucleotide (ODN) TTAGGG (A151), an AIM2 inflammasome inhibitor, could abolish the elevation of AIM2-induced cleavage of inflammatory cytokines and pyroptosis. Orthotopic BLCA by AIM2-overexpressed cells exhibits a better response to Bacillus Calmette-Guérin (BCG) immunotherapy. Overall, AIM2 inflammasome activation can inhibit the BLCA tumorigenesis and enhance the therapeutic effect of BCG in BLCA. This study provides new insights into the anti-tumor effect of AIM2 inflammasome activation in BLCA and the immunotherapeutic strategy of BLCA development.

Identification of Biomarkers Related to Prognosis of Bladder Transitional Cell Carcinoma.

Bladder transitional cell carcinoma (BTCC) is highly fatal and generally has a poor prognosis. To improve the prognosis of patients with BTCC, it is particularly important to identify biomarkers related to the prognosis. In this study, differentially expressed messenger RNAs were obtained by analyzing relevant data of BTCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Next, hub genes that were suitable for correlation analysis with prognosis were determined through constructing a protein-protein interaction (PPI) network of differentially expressed genes and screening of major modules in the network. Finally, survival analysis of these hub genes found that three of them (CCNB1, ASPM, and ACTC1) were conspicuously related to the prognosis of patients with BTCC (p < 0.05). By combining the clinical features of BTCC and the expression levels of the three genes, univariate Cox and multivariate Cox regression analyses were performed and denoted that CCNB1 could be used as an independent prognostic factor for BTCC. This study provided potential biomarkers for the prognosis of BTCC as well as a theoretical basis for subsequent prognosis-related research.

Scrotoscopy and traditional open surgery shows a high degree of consistency in the diagnosis of testicular torsion: An initial report.

Traditional open surgery (OS) is usually necessary when testicular torsion (TT) cannot be excluded by scrotal ultrasound. Scrotoscopy has been used as a minimally invasive technique to diagnose or treat scrotal diseases, and it may also play a role in diagnosing TT.A retrospective analysis was performed for patients with TT to evaluate the consistency of scrotoscopy and OS in the diagnosis of TT. In the cases where preoperational Color Doppler ultrasonography was performed, scrotoscopy, open surgery, and confirmed TT were included for future analysis.A total of 43 patients were studied. Twisted testes were retained in 11 cases (25.59%), and the remaining 32 patients (74.41%) underwent orchiectomy. There were significant differences in the diagnostic value between the grading of scrotoscopy and ultrasound, as well as between ultrasound grading and blood supply grading (BSG) (both P < .05). However, no significant difference was observed between the grading of scrotoscopy and BSG in traditional OS (P > .05), but a high degree of consistency existed between scrotoscopy grading and BSG in traditional OS (Kappa = 0.733, P ≤ .001).Our limited data indicate that the diagnosis of testicular torsion by scrotoscopy is highly consistent with that of traditional surgical exploration. Therefore, further studies are necessary to confirm its application value in the future. Scrotoscopy may have potential application value for the patients whom testicular torsion are insufficiently diagnosed but cannot be excluded.

Scrotoscopy exploration of testicular rupture: A pilot study.

To examine whether scrotoscopy could be used to diagnose testicular rupture (TR) with accuracy.This retrospective study included all patients receiving scrotoscopy followed by immediate open exploration (OE) for suspected TR at two Chinese tertiary care centers between March 2014 and March 2018.Fifteen patients suspected of having TR were included. TR was considered in 8 patients (8/15) via emergency scrotal ultrasound (ESU) examination. Of these 8 patients, 6 cases as well as 3 other cases, a total of 9 cases (9/15) were confirmed TR by scrotoscopy and OE; the remaining 6 patients (6/15) were found disease free. The presence/absence of TR was identified correctly with scrotoscopy in all 15 cases. The rupture size of the testicular tunica albuginea (TTA) varied from 0.5 to 2 cm. Only 3 cases (3/15) had scrotal wall edema and all quickly recovered. The testis was normal in size and blood flow at 6-month follow-up visit.Scrotoscopy accurately diagnoses TR, and may avoid unnecessary OE, especially for the patients confirmed free of disease.

Individualized minimally invasive treatment for adult testicular hydrocele: A pilot study.

BACKGROUND: Hydrocelectomy is the gold standard for the treatment of hydrocele, but it often causes complications after surgery, including hematoma, infection, persistent swelling, hydrocele recurrence, and chronic pain. In recent years, several methods for minimally invasive treatment of hydrocele have been introduced, but they all have limitations. Herein, we introduce a new method of individualized minimally invasive treatment for hydrocele. AIM: To present a new method for the treatment of adult testicular hydrocele. METHODS: Fifty-two adult patients with idiopathic testicular hydrocele were included. The key point of this procedure was that the scope of the resection of the sheath of the tunica vaginalis was determined according to the maximum diameter (d) of the effusion measured by ultrasound and the maximum diameter of the portion of the sheath pulled out of the scrotum was approximately πd/2. The surgical procedure consisted of a 2-cm incision in the anterior wall of the scrotum, drainage of the effusion, and dissection of part of the sheath of the tunica vaginalis. After the sheath was peeled away to the predetermined target extent, the pulled-out sheath was removed. The intraoperative findings and postoperative complications were analyzed. RESULTS: All patients were successfully treated with a median operation time of 18 min. The median maximum diameter of the effusion on ultrasound was 3.5 cm, and the median maximum diameter of the resected sheath was 5.5 cm. Complications occurred in four (7.7%) patients: two (3.8%) cases of mild scrotal edema, one (1.9%) case of scrotal hematoma, and one (1.9%) case of wound infection. All of the complications were grade I-II. Recurrent hydrocele, chronic scrotal pain, and testicular atrophy were not observed during a median follow-up of 12 mo. CONCLUSION: We report a new technique for individualized treatment of testicular hydrocele, which is quantitative and minimally invasive and yields good outcomes. Further study is warranted to verify its potential value in clinical practice.