High expression of eIF4A1 predicts unfavorable prognosis in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a worldwide malignancy with high morbidity and mortality. Translation initiation factor 4A1 (eIF4A1), which is an ATP-dependent RNA helicase as a part of eIF4F complex, has been linked to malignant transformation and progression, and a variety of cancers display dysregulation of this enzyme. However, its role in ccRCC remains unclear. In our study, we examined its potential effects in ccRCC. METHODS: Based on Proteomic data, TCGA and ONCOMINE database, RCC cell lines and tissues, the expression of eIF4A1 between ccRCC and normal tissues were investigated. A correlation was evaluated between the prognostic model for OS and ccRCC progression. Analysis of functional enrichment and PPI network were performed. After examining differentially expressed genes between the eIF4A1 high and low-expression groups, we performed GSEA analysis. Furthermore, we investigated immune cell infiltration of eIF4A1. Then we determined eIF4A1 functions in the establishment and maintenance of cell viability, migration and invasion of cell lines. Flow cytometry was utilized to detect cell cycle. RESULTS: The eIF4A1 was up-regulated in ccRCC tissues and cell lines. An increased level of eIF4A1 was linked to lower survival rates and impaired immunity. Depletion of eIF4A1 could arrest tumor cells in G1 phase, so as to seriously limit cell proliferation and weaken the capacity of cell migration. CONCLUSION: ccRCC patients with high eIF4A1 expression are at increased risk of poor prognosis, furthermore eIF4A1 plays a prominent role in facilitating tumor cell proliferation and migration which may further be a potential prognostic biomarker and therapeutic target.

Changing trends in the causes and management of male urethral stricture disease in China: an observational descriptive study from 13 centres.

OBJECTIVE: To determine whether there have been any changes in the causes and management of urethral strictures in China. PATIENTS AND METHODS: The data from 4,764 men with urethral stricture disease who underwent treatment at 13 medical centres in China between 2005 and 2010 were retrospectively collected. The databases were analysed for the possible causes, site and treatment techniques for the urethral stricture, as well as for changes in the causes and management of urethral strictures. RESULTS: The most common cause of urethral strictures was trauma, which occurred in 2,466 patients (51.76%). The second most common cause was iatrogenic injures, which occurred in 1,643 patients (34.49%). The most common techniques to treat urethral strictures were endourological surgery (1,740, 36.52%), anastomotic urethroplasty (1,498, 31.44%) and substitution urethroplasty (1,039, 21.81%). A comparison between the first 3 years and the last 3 years showed that the constituent ratio of endourological surgery decreased from 54% to 32.75%, whereas the constituent ratios of anastomotic urethroplasty and substitution urethroplasty increased from 26.73% and 19.18% to 39.93% and 27.32%, respectively (P < 0.05). CONCLUSIONS: During recent years, there has been an increase in the incidence of urethral strictures caused by trauma and iatrogenic injury. Endourological urethral surgery rates decreased significantly, and open urethroplasty rates increased significantly during the last 3 years.

Perioperative, functional, and oncologic outcomes of minimally-invasive surgery for highly complex renal tumors (RENAL or PADUA score ≥ 10): an evidence-based analysis.

The primary objective of the current study is to undertake a comparative analysis of the effectiveness and safety of minimally-invasive partial nephrectomy (MIPN; including laparoscopic and robotic approaches) and open partial nephrectomy (OPN) for the treatment of highly complex renal tumors (defined as PADUA or RENAL score ≥ 10). A comprehensive search was conducted in four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) to identify relevant studies published in the English language up to April 2023. The current study employed Review Manager 5.4 and encompassed controlled trials of both MIPN and OPN for the treatment of highly complex renal tumors. This study comprised a total of eight comparative trials involving 1161 patients. MIPN demonstrated a significant reduction in length of hospital stay (weighted mean difference [WMD] - 2.08 days, 95% confidence interval [CI] - 2.48, - 1.68; p < 0.00001), blood loss (WMD - 39.86 mL, 95% CI - 75.32, - 4.39; p = 0.03), transfusion rates (odds ratio [OR] 0.30, 95% CI 0.13, 0.71; p = 0.006), and overall complications (OR 0.46, 95% CI 0.31, 0.70; p = 0.0003). However, there were no significant differences between MIPN and OPN in terms of operative time, warm ischemia time, conversion to radical nephrectomy rates, renal functional and oncologic outcomes. This study reveals that MIPN presents several benefits in comparison to OPN, including decreased length of hospital stay, blood loss, transfusion rates, and complications, while still offering renal functional and oncological outcomes that are comparable to those of OPN in patients with highly complex renal tumors.

Acute kidney injury caused by consumption of melamine-contaminated infant formula in 47 children: a multi-institutional experience in diagnosis, treatment and follow-up.

Since the spring of 2008, an epidemic of urinary tract stones was noted among children in China. This is believed to be associated with consumption melamine-contaminated powdered formula. A few patients presented with acute kidney injury (AKI) due to bilateral renal or ureteral calculi requiring surgical intervention to relieve the obstruction. We retrospectively analyzed clinical and laboratory data, ultrasonograms and treatment methods in children with melamine-induced urolithiasis and AKI who were hospitalized at seven hospitals from September to November 2008 in Gansu Province, China. Treatment given included conservative treatment, cystoscopic or urethroscopic lithotripsy, retrograde ureteral catheterization, ureterolithotomy and nephrostomy. Patients were monitored postoperatively with data of ultrasonography, urinalysis and blood and urine biochemistry. The mean age of the 47 children was 10 months (mean ± SD, 10.83 ± 5.11 months). Thirty-four (72.34%) were male. Calculi size ranged from 3 to 14 mm in diameter. Nine patients (19.15%) were successfully treated with conservative treatment; 32 (68.09%) underwent retrograde ureteral catheterization and eight had simultaneous cystoscopic or urethroscopic stone removal; four were successfully treated with ureterolithotomy, and 1 underwent percutaneous nephrostomy. Thirty-eight patients were followed up for a mean ± SD of 18.50 ± 5.27 months and their renal functions were found to have completely recovered. Five (13.16%) cases had residual renal stones with diameter ranging from 2 to 4 mm. Therefore, this study has demonstrated that melamine-induced urolithiasis could lead to AKI. Removing obstruction promptly by surgical intervention has been found to be effective with satisfactory outcomes observed at mean follow-up period of 18-month. However, residual renal stone remained in 13.16% of the cases which required continued close observation.

Intravesical Bacillus Calmette-Guérin versus epirubicin for Ta and T1 bladder cancer.

BACKGROUND: Bladder cancer accounts for approximately 4.4% of adult malignancies, and approximately 80% of bladder cancer presents initially as transitional cell carcinoma that is confined to the urothelium (stage Ta) or lamina propria (stage T1). Intravesical administration of Bacillus Calmette-Guérin (BCG) and epirubicin (EPI) has been proven to reduce tumour recurrence and prevent or delay progression to muscle invasion and metastases. However, comparison of the effectiveness and safety of intravesical BCG and EPI in bladder cancer has yet to be explored. OBJECTIVES: To compare the effectiveness and safety of BCG with EPI in the treatment of Ta and T1 bladder cancer. SEARCH STRATEGY: A comprehensive search of MEDLINE (1966 to April 2010), EMBASE (1980 to April 2010), Health Services Technology, Administration, and Research (HealthSTAR), the Cochrane Central Register of Controlled Trials (CENTRAL), CancerLit, and Database of Abstracts of Reviews of Effectiveness (DARE), was performed, and handsearching of relevant journals was undertaken. SELECTION CRITERIA: All randomised or quasi-randomised trials (in which allocation was obtained by alternation - e.g., alternate medical records, date of birth, or other predictable methods) in patients with Ta or T1 bladder cancer that compared intravesical BCG with EPI were included. No language restrictions were applied. DATA COLLECTION AND ANALYSIS: Trial eligibility, methodological quality and data extraction were assessed independently by two reviewers. We compared dichotomous outcomes (frequency of tumour recurrence, progressive disease by stage, mortality, distant metastases, local and systemic adverse effects, treatment delayed or stopped due to adverse effects) using risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: Five trials of 1111 participants were included in this review. For BCG, 549 patients were treated, and 562 with EPI. Of the evaluated patients, 35.5% (195/549) in the BCG group and 51.4% (289/562) in the EPI group had tumour recurrence (P < 0.05). For disease progression (BCG, 44/549; EPI, 58/562) and distant metastases (BCG, 23/487; EPI, 31/495), there were no significant differences (P = 0.19 and P = 0.29, respectively). Only two trials, including 769 patients, had sufficient data for us to analyze disease-specific (BCG, 22/383; EPI, 26/386) and overall mortality (BCG, 125/383; EPI, 147/386). Neither comparison was significant (P = 0.93 and P = 0.12, respectively). In four studies reporting toxicity, BCG was associated with significantly more drug-induced cystitis [BCG, 54.1% (232/429); EPI, 31.7% (140/441)] and haematuria [BCG, 30.8% (132/429); EPI, 16.1% (71/440)]. Similarly, in three studies reporting systemic toxicity, BCG had significantly higher toxicity than the EPI (34.8% (134/385) versus 1.3% (5/393), respectively). In a meta-analysis comparing 'treatment delayed or stopped' (BCG, 40/431; EPI, 33/441), there was no significant difference between BCG and EPI treatments (P = 0.82). AUTHORS' CONCLUSIONS: The data from the present meta-analysis indicate that intravesical BCG treatment is more efficacious than EPI in reducing tumour recurrence for Ta and T1 bladder cancer. However, BCG appears to be associated with a higher incidence of adverse effects, such as drug-induced cystitis, haematuria and systemic toxicity, than EPI. The overall quality of the evidence is rather low. Well-designed, high quality randomised controlled trials with good allocation concealment are required.

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.

Free graft two-stage urethroplasty for hypospadias repair.

OBJECTIVE: To evaluate the effectiveness of free graft transplantation two-stage urethroplasty for hypospadias repair. METHODS: Fifty-eight cases with different types of hypospadias including 10 subcoronal, 36 penile shaft, 9 scrotal, and 3 perineal were treated with free full-thickness skin graft or (and) buccal mucosal graft transplantation two-stage urethroplasty. Of 58 cases, 45 were new cases, 13 had history of previous failed surgeries. Operative procedure included two stages: the first stage is to correct penile curvature (chordee), prepare transplanting bed, harvest and prepare full-thickness skin graft, buccal mucosal graft, and perform graft transplantation. The second stage is to complete urethroplasty and glanuloplasty. RESULTS: After the first stage operation, 56 of 58 cases (96.6%) were successful with grafts healing well, another 2 foreskin grafts got gangrened. After the second stage operation on 56 cases, 5 cases failed with newly formed urethras opened due to infection, 8 cases had fistulas, 43 (76.8%) cases healed well. CONCLUSIONS: Free graft transplantation two-stage urethroplasty for hypospadias repair is a kind of effective treatment with broad indication, comparatively high success rate, less complications and good cosmatic results, indicative of various types of hypospadias repair.

[Synergistic effects of paclitaxel and gemcitabine on androgen-independent prostate cancer].

OBJECTIVE: To observe the synergistic effects of paclitaxel (PA) and gemcitabine (GE) in vitro and in vivo on prostate cancer cell line PC-3. METHODS: Cell morphological observation, MTT assay, flow cytometry, and immunocytochemical method were used to observe the effects of 1+/-10(-6) mol/L, 1 x 10(-7) mol/L and 1 x 10(-8) mol/L PA and 1 x 10(-7) mol/L, 1 x 10(-8) mol/L and 1 x 10(-9) mol/L GE on prostate cancer cell line PC-3 in vitro in a single or combined administration for 48 h. Male BALB/C-nu mice bearing PC-3 prostate cancer were treated with docetaxol and retinoic acid singly or synergistically, followed by measurement of the body weight and immunohistochemical examination of serum prostate specific antigen (PSA) and PSA expression in the implanted tumors. RESULTS: GE at the concentration of 1 x 10(-8) mol/L significantly enhanced the effect of PA above 1 x 10(-7) mol/L in inducing growth inhibition (with an inhibition rate over 50.8%+/-4.2%, P<0.05) and apoptosis (apoptosis rate over 22.9%+/-2.3%, P<0.05) of PC-3 cells and in down-regulating the expression of cyclin D1 (expression rate no higher than 9.6%+/-1.6%, P<0.01) in PC-3 cells. GE lowered the rate of PA-induced cell cycle arrest at G(2)/M phase from 70.3%+/-9.7% to 38.2%+/-4.2%, and partially reversed the G(2)/M arrest (P<0.01). Synergistic treatment of the tumor-bearing mice caused little change in the body weight, but the serum PSA (51+/-14 ng/ml), implanted tumor mass (3.2+/-0.5 g) and PSA expression in the tumors (30%+/-3.7%) were all decreased significantly in comparison with the control mice (21.6+/-1.7 g). CONCLUSIONS: GE can enhance PA-induced tumor cell growth suppression and apoptosis in a synergistic manner both in vitro and in vivo, suggesting their great potential in clinical treatment of androgen-independent prostate cancer.

Chemiluminescence determination of melamine with Luminol-K3Fe(CN)6 system.

A sensitive chemiluminescence (CL) method was developed for determining melamine in urine and plasma samples based on the fact that melamine can remarkably enhance the chemiluminescence of Luminol-K3 Fe(CN)6 system in alkaline medium. The determination conditions were optimized. Under optimum conditions, the chemiluminescence intensity had a good linear relationship with melamine in the range of 9.0 × 10-9 - 7.0 × 10-6 g/mL with a correlation coefficient of 0.9992. The detection limits (3σ) were 3.54 ng/mL for urine sample and 6.58 ng/mL for plasma sample. The average recoveries of melamine were 102.6% for urine sample and 95.1% for plasma sample. Melamine in samples was extracted with liquid-liquid extraction procedures and the assay results coincided very well with that determined with flow injection chemiluminescence method. The method provides a reproducible and stable approach for sensitive detection and quantification of melamine in urine and plasma samples.