N6-methyladenosine-modified circ_104797 sustains cisplatin resistance in bladder cancer through acting as RNA sponges.

BACKGROUND: Bladder cancer (BCa) ranks among the predominant malignancies affecting the urinary system. Cisplatin (CDDP) remains a cornerstone therapeutic agent for BCa management. Recent insights suggest pivotal roles of circular RNA (circRNA) and N6-methyladenosine (m6A) in modulating CDDP resistance in BCa, emphasizing the importance of elucidating these pathways to optimize cisplatin-based treatments. METHODS: Comprehensive bioinformatics assessments were undertaken to discern circ_104797 expression patterns, its specific interaction domains, and m6A motifs. These findings were subsequently corroborated through experimental validations. To ascertain the functional implications of circ_104797 in BCa metastasis, in vivo assays employing CRISPR/dCas13b-ALKBH5 were conducted. Techniques, such as RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assays, and western blotting, were employed to delineate the underlying molecular intricacies. RESULTS: Our investigations revealed an elevated expression of circ_104797 in CDDP-resistant BCa cells, underscoring its pivotal role in sustaining cisplatin resistance. Remarkably, demethylation of circ_104797 markedly augmented the potency of cisplatin-mediated apoptosis. The amplification of circ_104797 in CDDP-resistant cells was attributed to enhanced RNA stability, stemming from an augmented m6A level at a distinct adenosine within circ_104797. Delving deeper, we discerned that circ_104797 functioned as a microRNA reservoir, specifically sequestering miR-103a and miR-660-3p, thereby potentiating cisplatin resistance. CONCLUSIONS: Our findings unveil a previously uncharted mechanism underpinning cisplatin resistance and advocate the potential therapeutic targeting of circ_104797 in cisplatin-administered patients with BCa, offering a promising avenue for advanced BCa management.

MALAT1 promotes FOXA1 degradation by competitively binding to miR-216a-5p and enhancing neuroendocrine differentiation in prostate cancer.

OBJECTIVES: Prostate cancer (PC) is a leading cause of cancer-related death in males worldwide. Neuroendocrine differentiation (NED) is a feature of PC that often goes undetected and is associated with poor patient outcomes. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs/miRs), and messenger RNAs (mRNAs) play important roles in the development and progression of PC. METHODS: In this study, we used transcriptome sequencing and bioinformatics analysis to identify key regulators of NED in PC. Specifically, we examined the expression of PC-related lncRNAs, miRNAs, and mRNAs in PC cells and correlated these findings with NED phenotypes. RESULTS: Our data revealed that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and zinc finger protein 91 (ZFP91) were upregulated in PC, while miR-216a-5p was down-regulated. Ectopic expression of MALAT1 induced NED and promoted malignant phenotypes of PC cells. Furthermore, we found that MALAT1 competitively bound to miR-216a-5p, upregulated ZFP91, and promoted the degradation of forkhead box A1 (FOXA1), a key gene involved in NED of PC. CONCLUSION: Taken together, these results suggest that MALAT1 plays an oncogenic role in NED and metastasis of PC via the miR-216a-5p/ZFP91/FOXA1 pathway. Our study highlights the potential of targeting this pathway as a novel therapeutic strategy for PC.

Circ-SFMBT2 sponges miR-224-5p to induce ketamine-induced cystitis by up-regulating metadherin (MTDH).

There is increasing evidence that circular RNAs (circRNAs) play significant roles in various biological processes, yet few reports have examined their roles and molecular mechanisms in ketamine-induced cystitis (KIC). This study examines the possible molecular mechanisms underlying the circRNA-microRNA-mRNA regulatory network in the development of KIC. Transcriptome data were collected, and bioinformatics analysis was conducted to create a circRNA-miRNA-mRNA regulatory network (ceRNA network) associated with the occurrence of KIC. Human bladder epithelial cells (SV-HUC-1) were used in in vitro cell assays. The binding affinity among circ-SFMBT2, miR-224-5p, and Metadherin (MTDH) was identified. To investigate the effects of circ-SFMBT2/miR-224-5p/MTDH on bladder function, KIC mouse models were induced by intraperitoneal injection of ketamine, and gain- or loss-of-function experiments were conducted. Our results demonstrate that MTDH may be a key gene involved in the occurrence of KIC. Both bioinformatics analysis and in vitro cell assays verified that circ-SFMBT2 can competitively bind to miR-224-5p, and miR-224-5p can target and inhibit MTDH. In the bladder tissues of KIC mice, circ-SFMBT2 and MTDH were up-regulated, while miR-224-5p was down-regulated. Animal experiments further confirmed that circ-SFMBT2 can up-regulate MTDH expression by sponging miR-224-5p, thereby exacerbating bladder dysfunction in KIC mice. This study proved that circ-SFMBT2 up-regulates MTDH by competitively binding to miR-224-5p, thereby exacerbating the bladder dysfunction of KIC.

Efficacy and safety evaluation of complete intrafascial prostatectomy in suspected prostate cancer patients with dysuria: a retrospective cohort study.

Background: Suspected localized prostate cancer (PCa) patients with dysuria Complete intrafascial prostatectomy (CIP) can remove the whole prostate gland with the maximal retain of adjacent normal tissues around the prostate, and can be applied in some suspected localized prostate cancer (PCa) patients with dysuria. However, precious few studies have assessed the efficacy and safety of CIP in these patients without preoperative needle biopsies. Methods: In this retrospective single-arm cohort study, all 22 suspected PCa patients with dysuria who underwent CIP at our hospital were enrolled. The clinical data including age, prostate-specific antigen (PSA), free-serum PSA, prostate volume, perioperative and postoperative complications were collected. The PSA level at 6 weeks after CIP and recoveries of urinary continence and erectile function were acquired in the follow-up procedures, and were used as the main measurements of efficacy and safety for CIP respectively. Results: The patients had an average age of 71.91±8.29 years and an average preoperative PSA level of 10.75±4.25 ng/mL. The operations for all 22 patients were successfully completed. The average operation time was 135.20±41.44 min (range, 40.0-215.0 min), and the average blood loss volume was 128.64±145.09 mL. In total, 17 patients (77.27%) had PCa confirmed by postoperative pathology, and 5 patients (22.73%) had benign prostatic hyperplasia. The PSA level dropped to 0.010±0.004 ng/mL at 6 weeks after surgery. According to the loose criteria to assess urinary incontinence, the patients achieved continence rates of 63.6% immediately after the operation, 95.5% at 1 month, and 100% at 3 months. According to the strict criteria, the continence rates immediately, and at 1, 3, 6, and 9 months after surgery were 27.3%, 63.6%, 90.9%, 95.5%, and 100%, respectively. None of the patients complained of urinary obstruction symptoms after surgery. Before CIP, all the patients had erectile dysfunction and an International Index of Erectile Function 5 (IIEF-5) score of 9.64±5.91. After surgery, the patients had IIEF-5 scores at 3, 6, and 12 months of 5.45±4.43, 6.95±5.30, and 7.57±5.69, respectively. Conclusions: Although the study had some limitations, CIP may be a prudent option for patients with suspected localized PCa who also present with dysuria.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Dibutyltin (DBT) inhibits in vitro androgen biosynthesis of rat immature Leydig cells.

Dibutyltin (DBT) is an organotine widely applied in stabilizing plastics and de-worm poultry agents. But the effects of DBT on immature Leydig cells remain elusive. Thus, the present study aims to investigate whether in vitro exposure to DBT affects immature Leydig cell function of androgen production and delineate the underlying mechanisms. 35 days old rat immature Leydig cells were isolated and exposed to DBT at different concentrations (0, 0.1, 0.5, and 1 µM). It was found that 0.5 and 1 µM DBT lowered androgen production from immature Leydig cells under basal conditions. DBT at 1 µM lowered androgen production from immature Leydig cells under the stimulations from luteinizing hormone or 8-Br-cAMP. DBT at 1 µM lowered 22R-hydroxycholesterol and pregnenolone-mediated androgen production from immature Leydig cells. DBT at 0.1, 0.5, and 1 µM down-regulated the mRNA expression levels of Lhcgr, Star, Cyp11a1, Hsd3b1, and Nr5a1. Further investigation found that DBT at 1 µM directly inhibited CYP11A1 and 3ß-HSD1 enzyme activities. In conclusion, this study told us that in vitro exposure to DBT inhibited androgen biosynthesis in immature Leydig cells by selectively interfering with the expressions and enzyme activities of CYP11A1 and 3ß-HSD1.

Construction of Decision Trees Based on Gene Expression Omnibus Data to Classify Bladder Cancer and Its Subtypes.

BACKGROUND Bladder cancer is a malignant tumor of the genitourinary system. Different subtypes of bladder cancer have different treatment methods and prognoses. Therefore, identifying hub genes affecting other genes is of great significance for the treatment of bladder cancer. MATERIAL AND METHODS We obtained expression profiles from the GSE13507 and GSE77952 datasets from the Gene Expression Omnibus database. First, principal component analysis was used to identify the difference in gene expression in different types of tissues. Differential expression analysis was used to find the differentially expressed genes between normal and tumor tissues, and between tumors with and without muscle infiltration. Further, based on differentially expressed genes, we constructed 2 decision trees for differentiating between tumor and normal tissues, and between muscle-infiltrating and non-muscle-infiltrating tumor tissues. A receiver operating characteristic curve was used to evaluate the prediction effect of the decision trees. RESULTS FAM107A and C8orf4 showed significantly lower expression in bladder cancer tissues than in normal tissues. Regarding muscle infiltration, CTHRC1 showed lower expression and HMGCS2 showed higher expression in non-muscle-infiltrating samples than in those with muscle infiltration. We constructed 2 decision trees for differentiating between tumor and normal tissue, and between tissues with and without muscle infiltration. Both decision trees showed good prediction results. CONCLUSIONS These newly discovered hub genes will be helpful in understanding the occurrence and development of different subtypes of bladder cancer, and will provide new therapeutic targets and biomarkers for bladder cancer.

[Transurethral enucleation and resection versus transurethral resection of the prostate in the treatment of high-risk benign prostatic hyperplasia].

OBJECTIVE: To investigate the clinical effect of transurethral enucleation and resection of the prostate (TUERP) versus that of transurethral resection of the prostate (TURP) in the treatment of high-risk BPH. METHODS: From June 2018 to December 2018, a total of 60 patients with high-risk BPH were randomly assigned to receive TUERP (n = 30) or TURP (n = 30). Comparisons were made between the two groups of patients in the operation time, intraoperative blood loss, volume of the resected prostate, and postoperative complications. RESULTS: Compared with the patients treated by TURP, those in the TUERP group showed a significantly shorter operation time(ï¼»76.2±15.9ï¼½ min vs ï¼»47.5±16.1ï¼½ min, P < 0.05), less intraoperative blood loss(ï¼»93.7±33.6 vs ï¼»60.5±25.4ï¼½ mlï¼½ ml, P < 0.05), but a larger volume of the resected prostate(ï¼»30.6±8.5ï¼½ g vs ï¼»42.3±12.2ï¼½ g, P < 0.05)， and a less incidence of postoperative complications, such as secondary bleeding, uracratia and urethrostenosis. CONCLUSIONS: Both TUERP and TURP are clinically effective for the treatment of high-risk BPH, but TUERP is even better than TURP for its advantages of shorter operation time, less intraoperative blood loss, larger volume of resected prostate, fewer postoperative complications, and less surgical trauma.

lncRNA small nucleolar RNA host gene 12 promotes renal cell carcinoma progression by modulating the miR­200c­5p/collagen type XI α1 chain pathway.

Renal cell carcinoma (RCC) is a primary malignant kidney cancer subtype. It has been suggested that long non­coding RNAs (lncRNAs) serve important roles in the progression of kidney cancer. In fact, the lncRNA small nucleolar RNA host gene 12 (SNHG12) was discovered to be overexpressed in various types of cancer. However, to the best of our knowledge, the role of SNHG12 in RCC remains unclear. The present study aimed to investigate the function of SNHG12 and its underlying molecular mechanism of action in RCC. In patient samples and datasets from The Cancer Genome Atlas. Reverse transcription­quantitative PCR, demonstrated that SNHG12 expression levels were upregulated in RCC tumor tissues, but not in normal kidney tissues. SNHG12 upregulation was also observed in RCC cell lines. Kaplan­Meier survival analysis indicated a poor prognosis for those patients with RCC who had upregulated SNHG12 expression levels. Following lentivirus transduction, SNHG12 was successfully knocked down (validated by western blot analysis) and cell migration and invasion assays were performed. SNHG12 knockdown markedly inhibited cell viability and invasion, while increasing apoptosis in both A498 and 786O cell lines. The results of the luciferase reporter assay suggested that SNHG12 exerted its role by sponging microRNA (miR)­200c­5p, which led to the upregulation of its target gene, collagen type XI α1 chain (COL11A1). This was further validated, as miR­200c­5p inhibition reduced the effects of SNHG12 downregulation on cell viability and apoptosis, without affecting SNHG12 expression levels. Furthermore, the findings indicated that SNHG12 may partially exert its role through COL11A1, which was also upregulated in RCC. In conclusion, the results of the present study suggested that the SNHG12/miR­200c­5p/COL11A1 axis may be crucial for RCC progression, which provided an insight into potential therapeutic strategies for RCC treatment.

Inhibition of malignant human bladder cancer phenotypes through the down-regulation of the long non-coding RNA SNHG7.

There is abundant evidence that long non-coding RNAs play important roles in the development of tumors. In the present study, our main aim was to explore the relationship between lncRNA SNHG7 and human bladder cancer cells, thus finding a novel target for bladder cancer therapy and diagnosis. Expression of lncRNA SNHG7 was evaluated using real-time quantitative polymerase chain reaction in bladder tumor tissues and paired adjacent normal tissues from 72 patients diagnosed with urothelial bladder carcinoma. We analyzed the differences in expression according to grading and staging. Human bladder cancer cell lines UMUC, 5637, T24 and SW780 were transiently transfected with lncRNA SNHG7-specific siRNA and negative control siRNA. The changes in malignant phenotypes in transfected bladder cancer cells were determined using CCK-8 assay, wound-healing assay and ELISA. We found that lncRNA SNHG7 was correlated with human bladder cancer. lncRNA SNHG7 was overexpressed in bladder cancer tissues compared to paired normal tissues and expression of SNHG7 was higher in high-grade than low-grade tumors. The malignant phenotypes were significantly inhibited when we inhibited expression of lncRNA SNHG7 in several bladder cell lines. SNHG7 plays an oncogenic role in human bladder cancer and may be a potential novel therapeutic target for treating bladder cancer.

Elevated expression of matrix metalloproteinase-9 is associated with bladder cancer pathogenesis.

OBJECTIVE: This study investigated the association between abnormal matrix metalloproteinase-9 (MMP-9) expression and bladder cancer (BC) development. MATERIALS AND METHODS: In a retrospective analysis, this study used tissue samples derived from 92 patients pathologically diagnosed with BC (experimental group), who were hospitalized between September 2012 and June 2014 at the Urinary Surgery of Department of Urology, Lanzhou University Second Hospital. As controls (control group), 63 normal pericancerous bladder mucosal tissues (3 cm distant form edge of BC foci) with confirmed pathology were selected from the same time period. Immunohistochemistry was employed to detect MMP-9 protein expression in the tissues and enzyme-linked immunosorbent assay was performed to measure MMP-9 protein levels in tissue samples of patients and control subjects. Finally, a meta-analysis was conducted to understand the overall impact of MMP-9 on BC pathogenesis. STATA 12.0 software (Stata Corp, College Station, TX, USA) was used for all statistical analyses. RESULTS: The MMP-9 positive expression rate in tissue samples and MMP-9 levels were significantly greater in the experimental group compared to the control group (both P < 0.001). The frequency of MMP-9 positive status showed statistically significant differences between G1 (low-grade) and G3 (high-grade) (P < 0.001), between G2 and G3 (P < 0.05), and between G1/G2 and G3 (P = 0.001). Our meta-analysis findings provided further evidence that MMP-9 positive expression status and MMP-9 levels in the experimental group were significantly higher than the control group (positive expressions: Odds ratio [OR] = 18.59, 95% confidence interval [95% CI] = 11.63-29.71, P < 0.001; expression levels: Standard mean difference = 1.51, 95%CI = 0.63-2.39, P = 0.001). The positive expression status of MMP-9 was notably lower in G1/G2 compared to G3 (OR = 0.24, 95%CI = 0.15-0.36, P < 0.001). CONCLUSION: Our study demonstrated that both positive expression status in tumor tissue and expression levels of MMP-9 are significantly elevated in BC patients and correlate with disease progression. Thus, MMP-9 can serve as a biomarker to determine the degree of BC malignancy.

A case report of Rosai-Dorfman disease with kidney involvement.

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder of unclear etiology, which commonly presented with the enlargement of lymph nodes of the neck and the head. Here, we report an unusual case of 77-year-old male patient presenting with left kidney lesion with several small enlarged lymph nodes around the abdominal aorta. The diagnosis of left kidney cancer was suspected and the patient underwent left laparoscopic exploration and lymph node biopsy. Only saponification of the renal surrounding fat and enlargement of the left renal pedicle and 5 abdominal aortic lymph nodes were found; no kidney cancer was found. Surrenalectomy and lymphadenectomy dissection were then performed and the left kidney was retained. Intraoperative frozen and postoperative pathology indicates Rosai-Dorfman disease. RDD with kidney involvement is uncommon, and its x-ray imaging appearances are atypical, and often resemble kidney cancer leading to kidney loss. A systematic literature review was also performed to investigate the x-ray imaging and treatment features of this disease.

Association of Vascular Endothelial Growth Factor Gene Polymorphism With Renal Cell Carcinoma Risk.

The conclusion of the relationship between vascular endothelial growth factor gene polymorphism and renal cell carcinoma risk was inconsistent. This study was performed to assess the relationship between vascular endothelial growth factor gene polymorphism and renal cell carcinoma risk using meta-analysis. The association studies were identified from PubMed, Embase, and Web of Science, and eligible studies were included and calculated. Ten studies were included for this meta-analysis. vascular endothelial growth factor (VEGF) +405G > CC allele and GG genotype were associated with renal cell carcinoma risk for overall populations in this meta-analysis (C allele: odds ratio = 1.18, 95% confidence interval: 1.05-1.33, P = .004; CC genotype: odds ratio = 1.20, 95% confidence interval: 0.96-1.50, P = .12; GG genotype: odds ratio = 0.79, 95% confidence interval: 0.67-0.93, P = .004). Furthermore, VEGF +936C>T gene polymorphism and VEGF -2578 C>A gene polymorphism were associated with renal cell carcinoma risk for overall populations (+936C>T: T allele: odds ratio = 1.16, 95% confidence interval: 1.05-1.29, P = .004; TT genotype: odds ratio = 1.25, 95% confidence interval: 1.02-1.52, P = .03; CC genotype: odds ratio = 0.86, 95% confidence interval: 0.75-0.98, P = .03; -2578 C>A: A allele: odds ratio = 1.26, 95% confidence interval: 1.15-1.38, P < .00001; AA genotype: odds ratio = 1.39, 95% confidence interval: 1.16-1.67, P = .0004; CC genotype: odds ratio = 0.75, 95% confidence interval: 0.61-0.92, P = .006). However, VEGF -634G>C, VEGF -460T>C, VEGF -1154 G>A, and VEGF +1612 G>A gene polymorphisms were not associated with renal cell carcinoma risk. In conclusion, VEGF +405G>CC allele and GG genotype, VEGF +936C>T gene polymorphism, and VEGF -2578 C>A gene polymorphism were associated with renal cell carcinoma risk for overall populations. However, more studies should be performed to assess this relationship in the future.

Correlations of Foxo3 and Foxo4 expressions with clinicopathological features and prognosis of bladder cancer.

OBJECTIVE: The study is performed to explore the correlations of forkhead box O3 (FoxO3) and forkhead box O4 (FoxO4) expressions with clinicopathological features and prognosis of bladder cancer. METHODS: Bladder cancer tissues and adjacent normal tissues from the recruited 222 patients were collected. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry were applied to determine the expressions of FoxO3 and FoxO4. Spearman correlation analysis was conducted to examine the correlation between the expressions of FoxO3 and FoxO4. All patients were followed up and overall survival (OS) and disease-free survival (DFS) were recorded. Kaplan-Meier survival curve was drawn to determine the associations of FoxO3 and FoxO4 expressions and postoperative survival. Cox proportional hazards model was conducted to analyze the risk factors for poor prognosis of bladder cancer. RESULTS: The mRNA and expressions of FoxO3 and FoxO4 proteins in the bladder cancer tissues were lower than that in the adjacent normal tissues (both P<0.05). The positive rates of FoxO3 and FoxO4 were lower in the patients with lymph node metastasis than that in the patients without lymph node metastasis (P<0.05), and significantly lower in the patients with non-muscle invasive bladder cancer (Tis-T1) than in those with non-muscle invasive bladder cancer (T2-T3) in TNM staging, and remarkably lower in the patients with high grade than in those with low grade in the histological type (P<0.05). Furthermore, the expressions of FoxO3 and FoxO4 were positively correlated in the bladder cancer tissues (P<0.05). Negative expressions of FoxO3 and FoxO4 and lymph node metastasis were the risk factors for the poor prognosis of bladder cancer. CONCLUSIONS: The FoxO3 and FoxO4 expressions may potentially associate with the clinicopathological features and prognosis of bladder cancer.

MicroRNA-21 in peripheral blood mononuclear cells as a novel biomarker in the diagnosis and prognosis of prostate cancer.

OBJECTIVE: To evaluate the effects of microRNA-21 (miR-21) in peripheral blood mononuclear cells (PBMC) in the diagnosis and prognosis of prostate cancer (PCa). METHODS: Proved by pathologic biopsy, 92 patients diagnosed with PCa and also underwent resection operation and 85 patients with benign prostatic hyperplasia (BPH) were selected in this study, as well as 97 healthy volunteers were chosen as the control group. PBMC were extracted to examine the relative expression of miR-21 by real time reverse transcriptase-polymerase chain reaction (RT-PCR). The relative operating characteristic (ROC) curves were drew to analyze the diagnosis value of PCa. The survival function curves were made by Kaplan-Meier method to show the miR-21 expression levels of PCa patients. The Log-rank test was adopted to compare the differences among the different groups. The Cox proportional hazard risk regression analysis was used to screen the independent factors affected the PCa patients. RESULTS: The expression levels of miR-21 in PCa group were increased compared to BPH and control group (P < 0.05). The expression of miR-21 was significantly correlated with the Gleason score, clinical stages, bone metastasis and tumor recurrence (all P < 0.05). ROC curves demonstrated that the area under the curve of PCa and BPH distinguished by the miR-21 were 0.974 and 95% confidence intervals (95% CI) were 0.956∼ 0.993. The sensitivity and specificity were 93.5% and 92.9%. ROC curves demonstrated that the area under the curve of PCa and control group distinguished by the miR-21 were 0.984 and 95% CI were 0.972∼ 0.997. The sensitivity and specificity were 94.6% and 92.8%. The results of Kaplan-Meier Method demonstrated that the miR-21 expression levels were related to the prognosis of PCa (all P < 0.05). The results of the COX analysis suggested that the miR-21 expression level, tumor recurrence and bone metastasis could be the independent factors affected the prognosis of PCa patients (all P < 0.05). CONCLUSION: miR-21 is highly expressed in the PCa patients, which could be the molecule biomarker of diagnosis and prognosis of PCa.

[Partial resection, inner thigh skin graft, and glans reconstruction for early-stage penile cancer: A report of 6 cases].

OBJECTIVE: To explore the optimal methods for the reconstruction and preservation of the glans after partial penis resection in the treatment of early-stage penile cancer. METHODS: Between January 2012 and June 2015, we treated 6 cases of early- stage penile cancer by partial penis resection, inner thigh skin graft, and glans reconstruction and followed them up for 0.5-3 years. RESULTS: The length of the penis before and after operation was ([6.5 ± 1.2] vs [4.5 ± 1.8] cm) in the flaccid state and ([12.8 ± 2.3] vs [9.1 ± 2.1] cm) in the erectile state. The sense of the reconstructed glans was completely recovered at 3 months after surgery. The glans skin was pale red and soft, nearly normal at 12 months, with no obvious graft contracture or scar formation. All the patients achieved normal erection and their partners were satisfied with their intercourse. No recurrence or metastasis was observed. CONCLUSION: The strategy of partial penis resection, inner thigh skin graft and glans reconstruction, simple, effective, and with few complications, is one of the best treatments of early-stage penile cancer, which not only ensures radical removal of the tumor but also maximally reserves the function of the organ.

Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer.

The present study investigated the potential association between matrix metalloproteinase-9 (MMP-9) expression and the pathogenesis of bladder cancer. The present study reviewed previous studies published in Chinese and English using predefined selection criteria, which identified high-quality studies concerning MMP-9 and bladder cancer. Statistical analyses of the data were conducted using Comprehensive Meta-Analysis software version 2.0. In total, 23 case-control studies were selected, which consisted of 1,040 bladder cancer patients and 244 healthy controls. The expression rates and protein levels of MMP-9 were significantly increased in bladder cancer patients compared with the healthy controls, which was demonstrated using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay-based methods. Furthermore, the expression rate of MMP-9 in histological G1/G2 grade bladder cancer tumors was significantly decreased compared with G3 tumors. Subgroup analysis based on ethnicity demonstrated that the rate of MMP-9 protein expression between bladder cancer patients and healthy controls was significantly different in African, Asian and Caucasian patients, which was identified using IHC. The MMP-9 protein levels in bladder cancer patients and healthy controls were significantly different between Asian and Caucasian patients, but not African patients. The differences between MMP-9 expression in ethnic groups were also evident in the expression rate of MMP-9 identified in histological G1/G2 grade tumors in Asian and Caucasian patients compared with G3 grade tumors, which was not evident in African patients. In conclusion, the present meta-analysis results markedly indicate that MMP-9 expression is associated with clinicopathological features of bladder cancer, suggesting that MMP-9 may be a useful biomarker in the diagnosis and clinical management of bladder cancer, and may be a valuable therapeutic target.

TGF-ß1-induced Fascin1 promotes cell invasion and metastasis of human 786-0 renal carcinoma cells.

OBJECTIVE: To investigate the effect of transforming growth factor-ß1 (TGF-ß1) on the expression of Fascin1 protein and its impact on cell invasion and metastasis in human renal carcinoma. METHODS: Renal tissue slices of 52 cases when undergoing radical nephrectomy were collected to be the observation group, and the normal renal tissues of 23 cases when undergoing nephrectomy due to trauma were collected to be the control group. The expressions of TGF-ß1 and Fascin1 were measured by immunohistochemical staining. Human renal carcinoma 786-0 cell line was selected as the study subject. The cells were divided into six groups including NT (no transfection), si-NC (transfection with pGenesil-1-con) si-Fascin1 (transfection with pGen-1-FSCN1) groups, and three corresponding groups: NT, si-NC and si-Fascin1 groups treated with TGF-ß1. RT-qPCR, Western-Blot, Transwell, and flow cytometry method were used in this study. RESULTS: The expressions of TGF-ß1 and Fascin1 in the observation group were significantly higher than those in the control group. The expression of TGF-ß1 was positively correlated with that of Fascin1. After 24 and 48h of treatment with TGF-ß1 (10ng/mL), the invasive and metastatic abilities of the 786-0 cells in the NT and si-NC groups were higher than those before the treatment (P<0.05). Comparing the three groups before TGF-ß1 treatment, the invasive and metastatic ability of 786-0 cells in the si-Fascin1 were significantly lower than those in the NT group and si-NC group (P<0.05). CONCLUSION: TGF-ß1 could induce the expressions of 786-0 Fascin1 mRNA and protein and thus improve the invasive and metastatic ability of human 786-0 renal carcinoma cell.

High-Level Expression of microRNA-21 in Peripheral Blood Mononuclear Cells Is a Diagnostic and Prognostic Marker in Prostate Cancer.

AIMS: Our study aimed to evaluate the diagnostic and prognostic values of microRNA-21 (miR-21) expression levels in peripheral blood mononuclear cells (PBMCs) for prostate cancer (PCa). METHODS: Between February 2010 and June 2014, 75 consecutive patients with localized PCa confirmed by radical prostatectomy and biopsy were enrolled as the case group. Among them, 25 patients were confirmed with recurrence or metastasis (R/M) (PCa with R/M group) and 50 patients without R/M (PCa without R/M group). During the same period, 75 healthy volunteers were enrolled as the control group. Blood was collected from all subjects, and PBMCs were isolated. Relative miR-21 expression levels from the PBMCs were determined by fluorescence real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The relative miR-21 expression levels in the preoperative case group was significantly higher than that in the postoperative case group and the control group (both p<0.001). miR-21 expression levels were associated with tumor differentiation, clinical stage, and lymph node metastasis (all p<0.001). Furthermore, miR-21 expression levels in PCa patients with R/M were significantly higher than that in PCa patients without R/M and healthy controls (both p<0.001). Receiver operating characteristic (ROC) curve analysis revealed that the cut-off point of miR-21 for diagnosis of PCa was 0.9 with a sensitivity of 87.5% and a specificity of 85.7%. CONCLUSIONS: Our study demonstrates that high miR-21 expression levels in PBMCs were correlated with the presence, recurrence, and metastasis of PCa and that this may be a useful biomarker for screening PCa and monitoring the risk of PCa recurrence and metastasis.

[Intervention effect of Tibetan patent medicine Ruyi Zhenbao pills in acute ischemic stroke in rats].

Ischemic stroke is a primary cause of death and long-term disability all over the world. This disease is resulted from ischemia and hypoxia in brain tissues because of insufficient blood supply and causes a series of physiochemical metabolism disorders and physiological dysfunction. Its high disability ratio has bright huge burdens to society, governments and families. However, there is not efficacious medicine to treat it. In this study, a right middle cerebral artery occlusion was established in rats to observe the multi-path and multi-aspect intervention effects of Tibetan patent medicine Ruyi Zhenbao pills in reducing injuries to Nissl bodies, cerebral edema and inflammatory reactions and preventing cellular apoptosis, in order to lay a foundation for defining its therapeutic mechanism in acute ischemic stroke.