Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

RAB10 promotes breast cancer proliferation migration and invasion predicting a poor prognosis for breast cancer.

RAB10, a member of the small GTPase family, has complex biological functions, but its role in breast cancer (BC) remains unclear. The aim of this study was to investigate the relationship between RAB10's role in BC, its biological functions, and BC prognosis. An online database was used to analyze the correlation between differential expression of RAB10 in BC and prognosis. The results of immunohistochemical assays in clinical cohorts were combined with the database analysis. The chi-square test and COX regression were employed to analyze the correlation between RAB10 and pathological features of BC. MTT, Transwell, and wound healing assays were conducted to detect BC cell proliferation, invasion, and metastatic ability. Bioinformatics techniques were employed to explore the correlation between RAB10 and BC tumor immune cell infiltration, and to speculate the biological function of RAB10 in BC and related signaling pathways. Our findings suggest that RAB10 expression is elevated in BC and is associated with HER2 status, indicating a poor prognosis for BC patients. RAB10 can promote the proliferation, migration, and invasion ability of BC cells in vitro. RAB10 is also associated with BC immune cell infiltration and interacts with multiple signaling pathways. RAB10 is a potential biomarker or molecular target for BC.

Decoding ceRNA regulatory network and autophagy-related genes in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common disease among aging males. We obtained BPH transcriptional signatures by high-throughput RNA sequencing analysis. Accordingly, we determined the differentially expressed RNAs (DERNAs) between BPH tissues and normal prostate tissues. WebGestalt and R package (clusterprofiler) was used to enrichment analysis. Clinical correlations were analyzed using Spearman's coefficient. TargetScan, ENCORI, miRNet, and miRDB databases were used to predict targets' relationships in ceRNA networks. Immunofluorescence staining and qRT-PCR analyses were performed to validate the findings. Microarray analysis of the datasets showed 369 DElncRNAs, 122 DEpseudogenes, 6 DEmiRNAs and 1358 DEmRNAs. DEmRNAs were particularly enriched in the autophagy-related pathways. Following the screening of DEmRNAs and autophagy-related genes (ARGs), 50 DEARGs were selected. MCODE analysis on Cytoscape was performed for the 50 DEARGs, and 3 hub genes (ATF4, XBP1, and PPP1R15A) were obtained. Spearman's correlation analysis showed that the mRNA expression of XBP1 correlated positively with age, total score, and storage score, but negatively with the maximum flow rate. Subsequently, the pseudogene/lncRNA- hsa-miR-222-3p-XBP1 pathway was identified. Our findings elucidate that the pseudogene/lncRNA-hsa-miR-222-3p-XBP1 pathway may play a regulatory role in the occurrence of BPH through autophagy.

Single-site multiport vs. conventional multiport robot-assisted radical prostatectomy: A propensity score matching comparative study.

Objective: Robot-assisted radical prostatectomy (RARP) is a dynamically evolving technique with its new evolution of single-site RARP. Here we sought to describe our extraperitoneal technique, named the single-site multiport RARP (ssmpRARP) using the da Vinci Si® platform and compare it with the transperitoneal conventional multiport RARP (cmpRARP). Materials and Methods: Data were retrospectively collected for patients who underwent RARP for localized prostate cancer from June 2020 to January 2022 in a single center. Propensity score matching was performed based on age, prostate size, body mass index, neoadjuvant hormonal therapy usage, prostate-specific antigen levels, and clinical T stage. The differences between the matched two groups were investigated. Results: Of the patients, 20 underwent ssmpRARP and 42 underwent cmpRARP during the period. After matching, 18 patients from each group were selected. Median follow-up was 7.8 months (2-12 months) for the ssmpRARP group, and 15.0 months (3-26 months) for cmpRARP. The demographic features between the two groups were comparable. The median total operative time, estimated blood loss, pathologic data, early follow-up outcomes, and hospitalization stays and costs were similar between the two groups. The ssmpRARP group tended to return to their bowel activities earlier (44.78 ± 10.83 h vs. 54.89 ± 12.97 h, p = 0.016). There were no significant differences in complication rates. Conclusions: We demonstrated the feasibility and safety of performing extraperitoneal ssmpRARP using the da Vinci Si® robotic platform. Our technique showed comparable short-term outcomes with the transperitoneal cmpRARP. Prospective trials and long-term follow-up are necessary to confirm these results.

METTL3 promotes prostatic hyperplasia by regulating PTEN expression in an m6A-YTHDF2-dependent manner.

Uncontrolled epithelial cell proliferation in the prostate transition zone and the hyper-accumulation of mesenchymal-like cells derived from the epithelial-mesenchymal transition (EMT) of prostatic epithelium are two key processes in benign prostatic hyperplasia (BPH). m6A RNA modification affects multiple cellular processes, including cell proliferation, apoptosis, and differentiation. In this study, the aberrant up-regulation of methylase METTL3 in BPH samples suggests its potential role in BPH development. Elevated m6A modification in the prostate of the BPH rat was partially reduced by METTL3 knockdown. METTL3 knockdown also partially reduced the prostatic epithelial thickness and prostate weight, significantly improved the histological features of the prostate, inhibited epithelial proliferation and EMT, and promoted apoptosis. In vitro, METTL3 knockdown decreased TGF-ß-stimulated BPH-1 cell proliferation, m6A modification, and EMT, whereas promoted cell apoptosis. METTL3 increased the m6A modification of PTEN and inhibited its expression through the reading protein YTHDF2. PTEN knockdown aggravated the molecular, cellular, and pathological alterations in the prostate of BPH rats and amplified TGF-ß-induced changes in BPH-1 cells. More importantly, PTEN knockdown partially abolished the improving effects of METTL3 knockdown both in vivo and in vitro. In conclusion, the level of m6A modification is elevated in BPH; the METTL3/YTHDF2/PTEN axis disturbs the balance between epithelial proliferation and apoptosis, promotes EMT, and accelerates BPH development in an m6A modification-related manner.

Histone Modifications and Chondrocyte Fate: Regulation and Therapeutic Implications.

The involvement of histone modifications in cartilage development, pathology and regeneration is becoming increasingly evident. Understanding the molecular mechanisms and consequences of histone modification enzymes in cartilage development, homeostasis and pathology provides fundamental and precise perspectives to interpret the biological behavior of chondrocytes during skeletal development and the pathogenesis of various cartilage related diseases. Candidate molecules or drugs that target histone modifying proteins have shown promising therapeutic potential in the treatment of cartilage lesions associated with joint degeneration and other chondropathies. In this review, we summarized the advances in the understanding of histone modifications in the regulation of chondrocyte fate, cartilage development and pathology, particularly the molecular writers, erasers and readers involved. In addition, we have highlighted recent studies on the use of small molecules and drugs to manipulate histone signals to regulate chondrocyte functions or treat cartilage lesions, in particular osteoarthritis (OA), and discussed their potential therapeutic benefits and limitations in preventing articular cartilage degeneration or promoting its repair or regeneration.

Expression and prognostic value of miR-92a in patients with gastric cancer.

MicroRNA (miR)-92 expression is often aberrant in human cancers. However, its expression in gastric carcinoma and its relation to clinicopathological features and prognosis are unclear.Tissue microarrays were constructed from 180 patients with gastric cancer (GC), who were undergoing radical resection. MiR-92a expression was detected using miRNA-locked nucleic acid in situ hybridization, and its correlation with clinicopathological features and overall survival was analyzed. MiR-92a expression was decreased in 13.9 % (25/180) of GC, increased in 81.1 % (146/180), and unchanged in 5.0 % (9/180), compared with paracancerous normal tissue (P < 0.001). Univariate analysis showed that high miR-92a expression, tumor stage, tumor status, node status, and tumor size were significant negative prognostic predictors for overall survival in patients with GC (P < 0.001, P < 0.001, P = 0.008, P < 0.001, and P = 0.001, respectively). High miR-92a expression still remained a significant predictor of shorter survival in stage II (n = 56, P = 0.001) and stage III (n = 92, P = 0.009) GC. Multivariate regression analysis demonstrated that tumor status (hazard ratio [HR], 3.10; 95 % confidence interval [CI], 1.51-6.37; P = 0.002), stage (HR, 3.54; 95 % CI, 1.65-7.63; P = 0.000), lymph node metastasis (HR, 2.83; 95 % CI, 1.88-4.28; P = 0.000), high expression of miR-92a (HR, 2.94; 95 % CI, 2.01-4.31; P = 0.000), and tumor size (HR, 2.34; 95 % CI, 1.45-3.79; P = 0.002) predicted shorter OS.High expression of miR-92a compared with adjacent normal tissues was associated with shorter OS. MiR-92a may thus be useful for evaluating prognosis and may provide a novel treatment target in patients with GC.