The ERH gene regulates migration and invasion in 5637 and T24 bladder cancer cells.

BACKGROUND: This study aimed to determine whether the enhancer of the rudimentary homolog (ERH) gene regulates cell migration and invasion in human bladder urothelial carcinoma (BUC) T24 cells and the underlying mechanism. METHODS: First, we knocked down ERH in BUC T24 and 5637 cells by shRNA and then used wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays to determine the migration and invasion ability after ERH was knocked down. Moreover, we used gene expression profiling chip analysis and further functional experiments to explore the possible mechanism through which ERH knockdown downregulated metastasis ability in T24 cells. RESULTS: Wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays all showed that the metastasis ability was significantly inhibited in human BUC T24 and 5637 cells with ERH knockdown. A gene expression profiling chip analysis in T24 cells showed that the MYC gene may be an important downstream target of the ERH gene, and the functional experiments showed that MYC is a functional target of ERH in BUC T24 cells. CONCLUSION: ERH knockdown could inhibit the metastasis of BUC T24 cells in vitro and in vivo. This study further explored the mechanism of the ERH gene in the metastasis of the T24 human bladder cancer cell line and found that ERH may regulate MYC gene expression. The results of this research provide a basis for the clinical application of ERH as a potential target for BUC treatment.

The prognostic significance of preoperative platelet-to-lymphocyte ratio and interleukin-6 level in non-muscle invasive bladder cancer.

BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) is the most prevalent type of bladder cancer, typically associated with a favorable prognosis and a risk of recurrence during the follow-up period. Inflammatory markers have been used to predict prognosis in various cancer types. The aim of this study was to explore the prognostic value of the readily accessible inflammatory markers, platelet-to-lymphocyte ratio (PLR) and interleukin-6 (IL-6), in NMIBC. METHODS: The study comprised a retrospective analysis of clinical data collected from NMIBC patients diagnosed between October 2018 and October 2020. PLR was calculated using the routine preoperative blood test results, and preoperative IL-6 levels were recorded. Receiver operating characteristic (ROC) curves were generated for PLR and IL-6 level and the optimal cut-off values were determined using Youden's index. Survival curves were generated to evaluate the association between PLR and IL-6, and recurrence-free survival (RFS), and univariate and multivariate analysis were performed using the Cox proportional hazards regression model. A nomogram and calibration curve were generated to assess the clinical significance of the model. RESULTS: The ROC curves demonstrated that PLR and IL-6 levels were significantly associated with tumor pathology grade, with area under the curve (AUC) values of 0.833 (95% CI 0.757, 0.910) for PLR and 0.724 (95% CI 0.622, 0.825) for IL-6 levels. PLR and IL-6 levels were also positively associated with tumor recurrence, with AUC values of 0.647 (95% CI 0.538, 0.756) and 0.846 (95% CI 0.769, 0.924), respectively. The survival curves indicated that patients with high PLR and high IL-6 levels had shorter RFS than those with low PLR and low IL-6 level (P < 0.01). Univariate Cox proportional hazards regression analysis showed that age, tumor size, tumor number, pathological grade, PLR and IL-6 were potential risk factors for NMIBC recurrence. Multivariate analysis further revealed that tumor number, smoking, PLR, and IL-6 were independent risk factors for NMIBC recurrence (P < 0.05). CONCLUSIONS: Preoperative peripheral blood inflammatory markers (PLR and IL-6) are useful predictors of RFS in NMIBC patients at the time of initial diagnosis. High PLR and high IL-6 were identified as independent risk factors for tumor recurrence and could serve as potential biological markers for prediction of NMIBC recurrence.

Validation of a Computerized Cognitive Training Tool to Assess Cognitive Impairment and Enable Differentiation Between Mild Cognitive Impairment and Dementia.

BACKGROUND: Age-related cognitive decline is a chronic, progressive process that requires active clinical management as cognitive status changes. Computerized cognitive training (CCT) provides cognitive exercises targeting specific cognitive domains delivered by computer or tablet. Meanwhile, CCT can be used to regularly monitor the cognitive status of patients, but it is not clear whether CCT can reliably assess cognitive ability or be used to diagnose different stages of cognitive impairment. OBJECTIVE: To investigate whether CCT can accurately monitor the cognitive status of patients with cognitive impairment as well as distinguish patients with dementia from patients with mild cognitive impairment (MCI). METHOD: We included 116 patients (42 dementia and 74 MCI) in final analysis. Cognitive ability was assessed by averaging the patient performance on the CCT to determine the Cognitive Index. The validity of the Cognitive Index was evaluated by its correlation with neuropsychological tests, and internal consistency was measured to assess the reliability. Additionally, we determined the diagnostic ability of the Cognitive Index to detect dementia using receiver operating characteristic (ROC) analysis. RESULTS: The Cognitive Index was highly correlated with the Montreal Cognitive Assessment (r = 0.812) and the Mini-Mental State Examination (r = 0.694), indicating good convergent validity, and the Cronbach's alpha coefficient was 0.936, indicating excellent internal consistency. The area under the ROC curve, sensitivity, and specificity of the Cognitive Index to diagnose dementia were 0.943, 83.3%, and 91.9%, respectively. CONCLUSIONS: CCT can be used to assess cognitive status and detect dementia in patients with cognitive impairment.

Assessment of Sexual Outcomes in Patients Undergoing Thulium Laser Prostate Surgery for Management of Benign Prostate Hyperplasia: A Systematic Review and Meta-analysis.

BACKGROUND: Thulium laser (Tm:YAG) prostate surgery is a safe and effective procedure with low morbidity and comparable clinical outcomes to those of transurethral resection of the prostate (TURP). However, the sexual function outcomes (erectile and ejaculatory function) have been scarcely studied. AIM: We aimed to assess the impact of Tm:YAG prostate surgery on sexual outcomes (erectile and ejaculatory function) and compare them with those patients undergoing TURP. MATERIAL AND METHODS: We searched digital databases like PUBMED, SCOPUS, CENTRAL and EMBASE using relevant keywords to identify comparative studies on TURP and non-comparative studies on Tm:YAG prostate surgery that assessed sexual outcomes. We performed qualitative and quantitative analyses with the extracted data. We carried out a meta-analysis to compare postoperative International Index of Erectile Function (IIEF-5) scores and incidences of retrograde ejaculation (RE) in patients undergoing either Tm:YAG or TURP. The pre-operative and post-operative IIEF-5 scores were pooled to estimate overall scores. RESULTS: We included 5 comparative and 8 non-comparative studies in this review. We found the postoperative IIEF-5 score improvements to be significantly higher in the Tm:YAG prostate surgery group than in the TURP group with a significant mean difference (MD) of 0.45 (95% CI, 0.18 to 0.72; P = .001). We found no significant associations between the procedures. The pooled OR for the association of RE was estimated at 0.90 (95% CI, 0.50 to 1.60; P = .71; I2 = 0%). CONCLUSION: Tm:YAG prostate surgery improves erectile function more than TURP, according to our findings. Tm:YAG prostate aided surgery also outperforms TURP in terms of preserving sexual function following surgery.However, We found similar or no difference in incidence of RE between Tm:YAG prostate surgery and TURP. Bibo L, Hao L, Pang K, et al. Assessment of Sexual Outcomes in Patients Undergoing Thulium Laser Prostate Surgery for Management of Benign Prostate Hyperplasia: A Systematic Review and Meta-analysis. Sex Med 2022;10:100483.

A network pharmacology perspective for deciphering potential mechanisms of action of Solanum nigrum L. in bladder cancer.

BACKGROUND: Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC). However, there are no previous pharmacological studies on the protective mechanisms of this activity of the plant. Thus, this study aimed to perform a systematic analysis and to predict the potential action mechanisms underlying S. nigrum activity in BC based on network pharmacology. METHODS: Based on network pharmacology, the active ingredients of S. nigrum and the corresponding targets were identified using the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform database, and BC-related genes were screened using GeneCards and the Online Mendelian Inheritance in Man database. In addition, ingredient-target (I-T) and protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, and then the pathways directly related to BC were integrated manually to reveal the pharmacological mechanism underlying S. nigrum-medicated therapeutic effects in BC. RESULTS: Seven active herbal ingredients from 39 components of S. nigrum were identified, which shared 77 common target genes related to BC. I-T network analysis revealed that quercetin was associated with all targets and that NCOA2 was targeted by four ingredients. Besides, interleukin 6 had the highest degree value in the PPI network, indicating a hub role. A subsequent gene enrichment analysis yielded 86 significant GO terms and 89 significant pathways, implying that S. nigrum had therapeutic benefits in BC through multi-pathway effects, including the HIF-1, TNF, P53, MAPK, PI3K/Akt, apoptosis and bladder cancer pathway. CONCLUSIONS: S. nigrum may mediate pharmacological effects in BC through multi-target and various signaling pathways. Further validation is required experimentally. Network pharmacology approach provides a predicative novel strategy to reveal the holistic mechanism of action of herbs.

Resveratrol inhibits hypertrophic scars formation by activating autophagy via the miR-4654/Rheb axis.

Hypertrophic scars (HSs) are a type of pathological scar which are induced by surgery, burn injuries or trauma during the healing process. Due to the high recurrence rates and strong invasive properties, HSs have become a major clinical issue. Resveratrol has been identified as a potential agent to suppress scar formation; however, the underlying mechanism of action remains unclear. Therefore, the present study aimed to investigate the effect of resveratrol on HS-derived fibroblasts (HSFBs) in vitro. MTT assay was performed to evaluate cell viability following the resveratrol treatment. Western blot and RT-qPCR analysis was used to identify the expression levels and the relationship among autophagic markers, miR-4654 and resveratrol treatment. Finally, GFP-LC3 stable HSFBs cells were generated to further assess the effect of resveratrol. The results revealed that resveratrol significantly induced cell death in a dose-dependent manner and induced autophagy by downregulating the expression levels of Rheb in HSFBs. Notably, microRNA-4654 (miR-4654) was significantly decreased in the HSFBs and re-upregulated by resveratrol treatment dose-dependently. Through the bioinformatic analysis and luciferase assay, miR-4654 was identified to directly target Rheb. Transfection studies showed that miR-4654 negative correlated with Rheb expression, suggesting that the autophagic process may be altered by the miR-4654/Rheb axis under the control of resveratrol. In conclusion, the results of the present study suggested that resveratrol may promote autophagy by upregulating miR-4654, which in turn may suppress Rheb expression via directly binding to the 3'-untranslated region of Rheb. These findings provided a novel insight into the development of potential therapeutic targets for HSs.

Guiding role of seminal tract anatomical study in transurethral seminal vesiculoscopy.

INTRODUCTION: There have been problems with low qualification operator-related complications and failures of transurethral seminal vesiculoscopy (TSV) in China. AIM: To study the guiding role of seminal tract anatomical study (STAS) in TSV. MATERIAL AND METHODS: We performed STAS to study the structure, morphology, duct trajectory, and anatomical relationships between the seminal vesicles and the adjacent tissue in pelvic specimens from 12 adult cadavers. Then the surgical effects and complications of 82 cases of TSV performed by 3 doctors were retrospectively studied to compare the difference between the two groups of before and after the anatomical study. RESULTS: The anatomical studies of the 12 adult cadaveric pelvis specimens identified the lengths and widths of the right- and left-side seminal vesicles and tracts. The TSV can treat lesions located in the distal seminal tract and vesicle, but proximal lesions cannot be reached, which is an anatomical limitation of this technique. There were significant differences in the surgical times and the surgical validity rates between the 2 groups. CONCLUSIONS: Our anatomical study of the seminal tract and seminal vesicles is valuable for guiding TSV in clinical practice.