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OBJECTIVE: Bladder cancer (BCa) is a malignant urological tumor with a high prevalence and poor prognosis. Extracellular vesicles (EVs) are increasingly becoming current hotspots owing to their involvement in cancer progression. This paper probed into the action of cancer-associated fibroblast-derived EVs (CAF-EVs) in the immune escape of BCa. METHODS: CAFs were identified by immunofluorescence. EVs were extracted from CAFs via ultracentrifugation and later characterized. BCa cells (T24 cell line) were co-cultured with CD8+ T cells and then treated with CAF-EVs. The uptake of EVs by T24 cells was examined by confocal laser microscopy. T24 cell apoptosis and invasion were assessed using flow cytometry and invasion assay. CD8+ T cell proliferation was evaluated using CFSE staining. The levels of cytokines (IFN-γ, IL-2, and TNF-α) were measured by ELISA. PD-L1 and PD-1 levels were determined utilizing RT-qPCR and flow cytometry. BCa mouse models were established to identify the effect of CAF-EVs on BCa progression in vivo. RESULTS: CAF-EVs decreased apoptosis and enhanced invasion of T24 cells, reduced proliferation of CD8+ T cells, and diminished levels of IFN-γ, IL-2, and TNF-α secreted by CD8+ T cells. CAF-EVs promoted the immune escape of T24 cells by carrying PD-L1. Downregulation of PDL1 expression in T24 cells or EVs partially counteracted the promotion of CAF-EVs on immune escape by reducing the binding of PD-L1 and PD-1. Additionally, CAF-EVs raised tumor volume and weight, upregulated PD-L1 expression, and weakened CD8+ T cell infiltration in BCa mice. CONCLUSION: CAF-EVs facilitate the immune escape of BCa by upregulating PD-L1/PD-1.

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Purpose Prostate cancer (PC) is a heterogeneous malignancy that greatly threatens man’s health. E3 ubiquitin-protein ligase neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) imparts an regulatory role in various malignancies. This study focused on the modulatory mechanism of NEDD4L in proliferation of prostate cancer cells (PCCs) via regulating histone demethylase plant homeodomain finger protein 8 (PHF8/KDM7B) through the ubiquitin–proteasome system. Methods The expression levels of NEDD4L, PHF8, H3 lysine 9 dimethylation (H3K9me2) and activating transcription factor 2 (ATF2) in PC tissues and cell lines were detected via real-time quantitative polymerase chain reaction and Western blotting. After transfection of pcDNA3.1-NEDD4L, pcDNA3.1-PHF8, and pcDNA3.1-ATF2 into PCCs, cell proliferation was assessed via the cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Interaction between NEDD4L and PHF8 was identified via the protein immunoprecipitation. The ubiquitination level of PHF8 was determined via the ubiquitination detection. The enrichments of H3K9me2 and PHF8 in the ATF2 promotor region were detected via the chromatin-immunoprecipitation assay. Results PHF8 and ATF2 were highly expressed while NEDD4L was poorly expressed in PC tissues and cells. NEDD4L overexpression reduced proliferation of PCCs. NEDD4L induced degradation of PHF8 via ubiquitination. PHF8 limited the enrichment of H3K9me2 in the ATF2 promotor region and enhanced ATF2 transcription. Up regulation of PHF8 or ATF2 abolished the inhibitory role of NEDD4L in proliferation of PCCs. Conclusion NEDD4L facilitated degradation of PHF8 to limit ATF2 transcription, thereby suppressing proliferation of PCCs. (AU)

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PURPOSE: Prostate cancer (PC) is a heterogeneous malignancy that greatly threatens man's health. E3 ubiquitin-protein ligase neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) imparts an regulatory role in various malignancies. This study focused on the modulatory mechanism of NEDD4L in proliferation of prostate cancer cells (PCCs) via regulating histone demethylase plant homeodomain finger protein 8 (PHF8/KDM7B) through the ubiquitin-proteasome system. METHODS: The expression levels of NEDD4L, PHF8, H3 lysine 9 dimethylation (H3K9me2) and activating transcription factor 2 (ATF2) in PC tissues and cell lines were detected via real-time quantitative polymerase chain reaction and Western blotting. After transfection of pcDNA3.1-NEDD4L, pcDNA3.1-PHF8, and pcDNA3.1-ATF2 into PCCs, cell proliferation was assessed via the cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Interaction between NEDD4L and PHF8 was identified via the protein immunoprecipitation. The ubiquitination level of PHF8 was determined via the ubiquitination detection. The enrichments of H3K9me2 and PHF8 in the ATF2 promotor region were detected via the chromatin-immunoprecipitation assay. RESULTS: PHF8 and ATF2 were highly expressed while NEDD4L was poorly expressed in PC tissues and cells. NEDD4L overexpression reduced proliferation of PCCs. NEDD4Linduced degradation of PHF8 via ubiquitination. PHF8 limited the enrichment of H3K9me2 in the ATF2 promotor region and enhanced ATF2 transcription. Upregulation of PHF8 or ATF2 abolished the inhibitory role of NEDD4L in proliferation of PCCs. CONCLUSION: NEDD4L facilitated degradation of PHF8 to limit ATF2 transcription, thereby suppressing proliferation of PCCs.

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Objective: To investigate the effect of percutaneous nephrolithotomy combined with needle nephrolithotomy on renal function and incidence of complications in patients with complex renal calculi. Methods: From March 2020 to March 2022, 88 patients with complex renal calculi were enrolled and divided into two groups. Percutaneous nephrolithotomy (PCNL) was performed in the control group, and percutaneous nephrolithotomy combined with needle nephrolithotomy was performed in the study group. Perioperative conditions, renal function parameters such as blood urea nitrogen (BUN), serum creatinine (Scr), and cystatin C (CysC) levels, inflammatory factors such as C-reactive protein (CRP) and procalcitonin (PCT) levels before surgery and 1 day after surgery were determined. The incidence of complications was statistically analyzed between two groups. Results: There was no significant difference in stone clearance rate between the two groups. The operation time and hospital stay in the study group were shorter than those in the control group. The intraoperative blood loss was less than that in the control group. The VAS score was lower than that in the control group. BUN, Scr, and CysC in the study group were not significantly different from those in the control group. CRP and PCT in the two groups at 1 d after surgery were higher than those before surgery, but CRP and PCT in the study group were lower than those in the control group. The incidence of complications in the study group was lower than that in the control group. Conclusion: Percutaneous nephrolithotomy combined with needle nephrolithotomy is effective and safe in the treatment of complex renal calculi.

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BACKGROUND: Bladder cancer (BCa) is a malignant tumor that occurs on the mucosa of the bladder, in which dysregulated long non-coding RNAs (lncRNAs) are involved. This study investigated the effect of lncRNA small nucleolar RNA host gene 1 (SNHG14) on the biological characteristics of BCa cells from microRNA (miR)-211-3p/ESM1 signaling axis. METHODS: BCa tissues and the matched normal tissues were collected to test SNHG14, miR-211-3p and ESM1 levels. SNHG14, miR-211-3p and ESM1 levels in BCa cell lines (T24, 5637, UMUC-3 and EJ) and normal bladder epithelial cells SV-HVC-1 were detected for screening the cell lines for follow-up experiments. T24 and UMUC-3 cells were transfected with different plasmids of SNHG14, miR-211-3p or ESM1 to observe the biological characteristics of BCa cells by MTT, colony formation, Transwell assays and flow cytometry. Tumor xenograft was implemented to inspect tumor growth in vivo. The targeting relationships of SNHG14, miR-211-3p and ESM1 were verified by bioinformatics software, RNA pull down assay and luciferase reporter assay. RESULTS: Enhanced SNHG14, ESM1 and suppressed miR-211-3p were found in BCa tissues and cells. SNHG14 up-regulated ESM1 via competitive binding with miR-211-3p. Decreased SNHG14 or up-regulated miR-211-3p depressed cell cycle entry, colony formation, invasion, migration and proliferation abilities, and facilitated apoptosis of BCa cells. Decreased SNHG14 or up-regulated miR-211-3p reduced the tumor volume and weight of nude mice with BCa, as well as promoted apoptosis and restrained proliferation of tumor cells. miR-211-3p inhibition or ESM1 overexpression reversed the effects of down-regulation of SNHG14 on BCa, and miR-211-3p up-regulation or ESM1 downregulation reversed the effect of SNHG14 overexpression on BCa. SNHG14 targeted miR-211-3p to regulate ESM1 expression. CONCLUSION: Our study highlights that silenced SNHG14 or elevated miR-211-3p represses the tumorigenic ability of BCa cells, which may be linked to ESM1 knockdown.

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OBJECTIVE: To investigate the relationship of the expression of vasodilator-stimulated phosphoprotein (VASP) with the metastasis and prognosis of prostate cancer. METHODS: Prostate cancer PC3 cells were infected with VASP shRNA and control shRNA lentiviruses, respectively. The invasive ability of the PC3 cells was determined by transwell migration assay, the expression of VASP in the prostate cancer tissue from 56 patients was detected by immunohistochemistry, and the survival rate of the patients was analyzed according to the VASP expression levels and follow-up data after radical prostatectomy. RESULTS: VASP shRNA lentivirus significantly inhibited the expression of VASP and decreased the invasive ability of the PC3 cells as compared with the results obtained in the scramble shRNA and blank control groups (P<0.05). The survival analysis of the 56 prostate cancer patients showed that the time of biochemical recurrence was markedly shorter in the VASP positive and strongly positive groups than in the VASP-negative cases (P<0.05), but with no statistically significant difference between the former two groups (P>0.05). CONCLUSIONS: VASP is involved in the regulation of the invasive ability of prostate cancer PC3 cells, and the differences in the VASP expression are related to the prognosis of prostate cancer.

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BACKGROUND: Although cystitis glandularis (CG) is a common benign urinary bladder epithelial abnormality, it remains unclear whether CG is a premalignant lesion. Cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) overexpression has recently been reported as a potential tumor initiator or promoter. We evaluated and compared COX-2 and Bcl-2 expression in CG, chronic cystitis (CC), and primary vesicle adenocarcinoma (ADC) tissues. METHODS: We conducted a retrospective study to investigate COX-2 and Bcl-2 levels in CG and ADC. We obtained tissue samples from 75 patients (including 11 cases of CC, 30 typical cases of CG (CGTP), 30 cases of intestinal CG (CGIT), and 4 cases of ADC) between 1989 and 2009 from the Surgical Pathology Archives of the No. 2 People's Hospital of Zhenjiang, affiliated with Jiangsu University. COX-2 and Bcl-2 immunohistochemical staining was performed on all tissues. Nine normal bladder epithelial specimens were evaluated as control samples. Correlations between COX-2 and Bcl-2 expression in CG were also analyzed. RESULTS: COX-2 and Bcl-2 expression was higher in the ADC group compared to other groups (p < 0.05). COX-2 and Bcl-2 levels were higher in the CGIT group compared to the CGTP group (p = 0.000 for both). The CGIT and CGTP groups both showed higher COX-2 expression compared to the CC group (p = 0.000 for both). There was no difference in Bcl-2 expression between the CGTP and CC groups (p = 0.452). Additionally, the difference in COX-2 and Bcl-2 expression between the control and CC groups was also insignificant (p = 0.668 and p = 0.097, respectively). Finally, we found that COX-2 and Bcl-2 levels were positively related (r = 0.648, p = 0.000). CONCLUSION: COX-2 and Bcl-2 overexpression in the CG group suggests that CG, particularly the intestinal type, may be a premalignant lesion that converts into a tumor in the presence of carcinogens.

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OBJECTIVES: To discuss the correlation of C-reactive protein (CRP) concentration in the EPS of chronic prostatitis (CP) patients with CP types, WBC count in EPS, lecithin corpuscles (LLZXT) and chronic prostatitis symptom index (CPSI). METHODS: According to the NIH classification standard, 196 cases of CP were diagnosed by the pro and post massage test (PPMT) and EPS routine, of which 68 were chronic bacterial prostatitis (Type II ), 76 inflammatory chronic non-bacterial prostatitis/chronic pelvic pain syndrome (Type III A) and 52 non-inflammatory chronic non-bacterial prostatitis/chronic pain syndrome (Type III B). Another 50 healthy volunteers were enrolled as normal controls. The CRP concentration in the EPS of all the patients was determined by immunoturbidimetry and 196 groups of data were obtained. RESULTS: The average concentration of CRP was significantly higher in the CP group ( [2.945 +/- 1.996] mg/L) than in the control ( [1.101 +/- 0.440] mg/L) (P < 0. 01) , and it decreased progressively from the Type II to Type III A and Type III B group, with statistical difference between Type III B and Type II or Type III A (P < 0. 01 ), but not between Type II and Type III A (P = 0.058). The CRP concentration was correlated negatively with LLZXT (r = -0.33, P < 0.01) and positively with WBC count (r = 0.63, P < 0.01) and the score on the first 6 items of CPSI (r = 0. 28, P < 0. 01). CONCLUSION: The CRP concentration in EPS, with its significant role in the pathogenesis of CP, may serve as a basis for the diagnosis and classification of CP as well as an objective index for assessing the therapeutic effect on the disease.

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