Lentivirus-Mediated Silencing of Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase 2 Inhibits Release of Inflammatory Cytokines and Apoptosis in Renal Tubular Epithelial Cells Via Inhibition of the TLR4/NF-kB Pathway in Renal Ischemia-Reperfusion Injury.

BACKGROUND/AIMS: Renal reperfusion injury occurs after the blood flow to the ischemic kidney is re-established under various clinical conditions, such as organ transplantation, renal artery stenosis, embolic disease, and the repair of descending aortic. The current study aims to explore the effects of src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) on the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells by regulating the TLR4/NF-κB signaling pathway in rats with renal ischemia-reperfusion (I/R) injury. METHODS: A total of 60 normal clean Sprague Dawley (SD) (WT) rats were used in this study. The levels of creatinine (Cr) and blood urea nitrogen (BUN) were determined using an automatic biochemical analyzer. The apoptosis in renal tissue was detected by TUNEL assay. The renal tubular epithelial cells of rats were cultured, infected and treated with different lentivirus vectors. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1ß and SHP27 were measured. Reverse transcription quantitative polymerases chain reaction and Western blot analysis were performed to measure the expression of relevant genes and proteins. Furthermore, the effect of SHP-2 on the proliferation, cell cycle and apoptosis of renal tubular epithelial cells was also investigated. RESULTS: In the serum of rats with renal I/R injury and prolonged reperfusion time, the contents of Cr and BUN were increased, the positive expression of SHP-2 was higher, the level of apoptosis was promoted, IL-6, TNF-α, IL-1ß and SHP27 expression in the serum was increased, the expression of SHP2, TLR4, NF-κB, IL-6, TNF-α and Bax was up-regulated, and the expression of Bcl-2 was down-regulated. Lentivirus-mediated silencing of SHP-2 promoted the proliferation of renal tubular epithelial cells, inhibited their apoptosis, and reduced the expression of inflammatory factors in these cells by functionally suppressing the TLR4/NF-κB signaling pathway. CONCLUSION: The results indicated that lentivirus-mediated silencing of SHP-2 inhibited the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells, and promoted the proliferation of these cells by inhibiting the TLR4/NF-κB signaling pathway in rats with renal I/R injury.

p21 and CK2 interaction-mediated HDAC2 phosphorylation modulates KLF4 acetylation to regulate bladder cancer cell proliferation.

Krüppel-like factor 4 (KLF4) is a transcription factor involved in both tumor suppression and oncogenesis as a transcriptional activator or repressor in a context-dependent manner. KLF4 acts as a regulator of p53 depending on p21 status in breast cancer. However, the mechanisms underlying the distinct role of KLF4 remain poorly understood. Here, we revealed that p21 depletion converted KLF4 from a cell cycle inhibitor to a promoter of bladder cancer cell proliferation. Additionally, KLF4 was acetylated in a p21-dependent manner to inhibit bladder cancer cell growth as a tumor suppressor. However, deacetylated KLF4 functioned as an oncogene promoting bladder cancer cell proliferation. Mechanistically, p21 and CK2 interaction, but not CK2 alone, enhanced HDAC2 phosphorylation and restricted KLF4 deacetylation and subsequent tumor promotion. Furthermore, we observed that KLF4 was acetylated by CBP/p300 and that overexpression of CBP resulted in KLF4 acetylation and tumor suppression even in p21-depleted bladder cancer cells. Moreover, we discovered that Notch-1 knockdown-induced KLF4 is acetylated form of KLF4, which may mediate Notch-1 function in bladder cancer cell proliferation. Our data demonstrate that KLF4 acts as a tumor suppressor or oncogene to activate or repress target gene transcription depending on its acetylation status, which is regulated by p21 and CK2 interaction-mediated HDAC2 phosphorylation. Targeting KLF4 at the post-transcriptional levels may provide novel insight for bladder cancer therapy.

[Application of retroperitoneal laparoscopic partial nephrectomy in renal carcinoma patients with intermediate risk PADUA score].

OBJECTIVE: To study the application of retroperitoneal laparoscopic partial nephrectomy in renal carcinoma patients with intermediate risk PADUA score. METHODS: From April 2005 to June 2011, 79 cases (48 males and 31 females) of intermediate risk PADUA score (range from 8 to 9 score) renal cell carcinoma were retrospectively analyzed. Mean age was (54 ± 9) years, mean tumor size was (2.8 ± 0.8) cm in diameter, with 37 cases on the left side and 42 cases on the right side. Tumor located anteriorly in 35 cases, and 44 cases were located posteriorly. Preoperative imaging examinations showed tumor invasion of the collecting system was dislocated or infiltrated by tumor invasion were in 13 cases, renal sinus were involved in 5 cases, tumor located near the renal hilum were in 10 cases. All of the 79 patients received retroperitoneal laparoscopic partial nephrectomy. RESULTS: The 79 cases were operated successfully without conversion to open surgery, no severe perioperative complications. The mean operation time was (105 ± 24) minutes, and the median of operation time was 115 minutes (range from 80 - 180 minutes), and mean warm ischemia time (WIT) was (20 ± 5) minutes, and mean blood loss was (24 ± 8) ml; mean postoperative hospital stay was (5.2 ± 1.5) days. Postoperative urinary leakage in 3 cases, symptoms disappeared one week after indwelling catheterization and ureteral catheter. Serum creatinine transient increased in 7 cases after surgery, and fell to normal range within 6 weeks. In a mean follow up for (34 ± 12) months (range from 10 to 84 months), estimated glomerular filtration rate (eGFR) 6 months after operation was no statistical significance compared with preoperation in 77 cases, another 2 patients' eGFR decreased by 30% and 35%. Postoperative renal function remained in CKD3 period and CKD2 period were in 2 cases respectively, none of these cases were treated with hemodialysis, and the remaining patients with normal renal function after surgery, no tumor recurrence and metastasis during follow-up in all cases. CONCLUSIONS: Treatment of retroperitoneal laparoscopic partial nephrectomy in renal carcinoma patients with intermediate risk PADUA score is safe and effective, but its long-term effects still need to study with large samples compare and long-term follow-up.

Efficacy of ultra-mini percutaneous nephrolithotomy and retrograde intrarenal surgery in the treatment of 2-3 cm lower calyceal stones / Eficacia de la nefrolitotomía percutánea ultramini y la cirugía intrarrenal retrógrada en el tratamiento de cálculos caliceales inferiores de 2-3 cm

Abstract We aimed to compare the efficacy and safety of ultra-mini percutaneous nephrolithotomy (UMP) and retrograde intrarenal surgery (RIRS) for the management of lower calyceal stones. A group of 136 patients with a single lower calyceal stone (2-3 cm in diameter) was divided into the UMP or RIRS groups. The average operation time in the RIRS group was significantly longer than that in the UMP group, and the intraoperative blood loss in the former was markedly less than that in the latter. Besides, in the RIRS group, the decreased value of postoperative Hb was obviously lower, the postoperative hospital stay was evidently shorter, and the total hospitalization expenses were markedly less than those in UMP group were. Moreover, the success rate of the first-stage lithotripsy in the UMP group was notably higher than that in RIRS group. The RIRS group had an obviously lower VAS score but a markedly higher BCS score than the UMP group six hours after surgery. At 24 h after operation, the levels of serum CRP, TNF-α and IL -6 in patients in both groups were remarkably increased, and they were evidently lower in the RIRS group than those in the UMP group were. Three days after surgery, the levels of serum CRP, TNF-α and IL -6 were notably lower in the UMP group than those in RIRS group were. RIRS and UMP are safe and effective in the treatment of 2-3 cm lower calyceal stones. The first-stage UMP is characterized by a high stone-free rate (SFR), short operation time and low postoperative infection risk, while RIRS is associated with less blood loss and low total expenses.

Resumen Nuestro objetivo fue comparar la eficacia y seguridad de la nefrolitotomía percutánea ultramini (UMP) y la cirugía intrarrenal retrógrada (CRIR) en el manejo quirúrgico de los cálculos caliceales inferiores. Un grupo de 136 pacientes con un solo cálculo calicial inferior (2-3 cm de diámetro) se dividió en un grupo UMP o un grupo CRIR. El tiempo de operación promedio en el grupo CRIR fue significativamente más largo que en el grupo UMP, y la pérdida de sangre intraoperatoria en el primero fue marcadamente menor que en el segundo. Además, en el grupo CRIR, el valor disminuido de la Hb postoperatoria fue obviamente menor, la estancia hospitalaria postoperatoria fue evidentemente más corta y los gastos totales de hospitalización fueron notablemente menores que los del grupo UMP. Además, la tasa de éxito de la litotricia de primera etapa en el grupo UMP fue notablemente más alta que en el grupo CRIR. El grupo CRIR tuvo una puntuación VAS obviamente más baja pero una puntuación BCS marcadamente más alta que el grupo UMP a seos horas después de la operación. A las 24 h después de la operación, los niveles séricos de PCR, TNF-α e IL -6 en los pacientes de ambos grupos aumentaron notablemente y fueron evidentemente más bajos en el grupo CRIR que en el grupo UMP. Tres días después de la operación, los niveles séricos de PCR, TNF-α e IL -6 fueron notablemente más bajos en el grupo UMP que en el grupo CRIR. Los procedimientos CRIR y el UMP son seguros y eficaces en el tratamiento de cálculos caliciales inferiores de 2-3 cm. El UMP de primera etapa se caracteriza por tener una tasa libre de cálculo (SFR) alta, un tiempo de operación corto y un riesgo de infección posoperatorio bajo, y el RIRS se caracteriza por una menor pérdida de sangre y gastos totales bajos.

Transurethral plasmakinetic resection of the prostate is a reliable minimal invasive technique for benign prostate hyperplasia: a meta-analysis of randomized controlled trials.

To evaluate the efficacy and safety of plasmakinetic resection of the prostate (PKRP) versus transurethral resection of the prostate (TURP) for the treatment of patients with benign prostate hyperplasia (BPH), a meta-analysis of randomized controlled trials was carried out. We searched PubMed, Embase, Web of Science and the Cochrane Library. The pooled estimates of maximum flow rate, International Prostate Symptom Score, operation time, catheterization time, irrigated volume, hospital stay, transurethral resection syndrome, transfusion, clot retention, urinary retention and urinary stricture were assessed. There was no notable difference in International Prostate Symptom Score between TURP and PKRP groups during the 1-month, 3 months, 6 months and 12 months follow-up period, while the pooled Q max at 1-month favored PKRP group. PKRP group was related to a lower risk rate of transurethral resection syndrome, transfusion and clot retention, and the catheterization time and operation time were also shorter than that of TURP. The irrigated volume, length of hospital stay, urinary retention and urinary stricture rate were similar between groups. In conclusion, our study suggests that the PKRP is a reliable minimal invasive technique and may anticipatorily prove to be an alternative electrosurgical procedure for the treatment of BPH.

Robot-Assisted Radical Prostatectomy vs. Open Retropubic Radical Prostatectomy for Prostate Cancer: A Systematic Review and Meta-analysis.

Open retropubic radical prostatectomy (ORP) remains the "gold standard" for surgical treatment of clinically localized prostate cancer (PCa). Robot-assisted radical prostatectomy (RARP) is a robotic surgery used worldwide. The aim of this study is to collect the data available in the literature on RARP and ORP, and further evaluate the overall safety and efficacy of RARP vs. ORP for the treatment of clinically localized PCa. A literature search was performed using electronic databases between January 2009 and October 2013. Clinical data such as operation duration, transfusion rate, positive surgical margins (PSM), nerve sparing, 3- and 12-month urinary continence, and potency were pooled to carry out meta-analysis. Six studies were enrolled for this meta-analysis. The operation duration of RARP group was longer than that of ORP group (weighted mean difference = 64.84). There was no statistically significant difference in the transfusion rate, PSM rate, and between RARP and ORP (transfusion rate, OR = 0.30; PSM rate, OR = 0.94). No significant difference was seen in 3- and 12-month urinary continence recovery (3 months, OR = 1.32; 12 months, OR = 1.30). There was a statistically significant difference in potency between the 3- and 12-month groups (3 months, OR = 2.80; 12 months, OR = 1.70). RARP is a safe and feasible surgical technique for the treatment of clinically localized PCa owing to the advantages of fewer perioperative complications and quicker patency recovery.

Conditional Knockout of Src Homology 2 Domain-containing Protein Tyrosine Phosphatase-2 in Myeloid Cells Attenuates Renal Fibrosis after Unilateral Ureter Obstruction.

BACKGROUND: Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) is a kind of intracellular protein tyrosine phosphatase. Studies have revealed its roles in various disease, however, whether SHP-2 involves in renal fibrosis remains unclear. The aim of this study was to explore the roles of myeloid cells SHP-2 in renal interstitial fibrosis. METHODS: Myeloid cells SHP-2 gene was conditionally knocked-out (CKO) in mice using loxP-Cre system, and renal interstitial fibrosis was induced by unilateral ureter obstruction (UUO). The total collagen deposition in the renal interstitium was assessed using picrosirius red stain. F4/80 immunostaing was used to evaluate macrophage infiltration in renal tubular interstitium. Quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay were used to analyze the production of cytokines in the kidney. Transferase-mediated dUTP nick-end labeling stain was used to assess the apoptotic renal tubular epithelial cells. RESULTS: Src homology 2 domain-containing protein tyrosine phosphatase-2 gene CKO in myeloid cells significantly reduced collagen deposition in the renal interstitium after UUO. Macrophage infiltration was evidently decreased in renal tubular interstitium of SHP-2 CKO mice. Meanwhile, the production of pro-inflammatory cytokines was significantly suppressed in SHP-2 CKO mice. However, no significant difference was observed in the number of apoptotic renal tubular epithelial cells between wild-type and SHP-2 CKO mice. CONCLUSIONS: Our observations suggested that SHP-2 in myeloid cells plays a pivotal role in the pathogenesis of renal fibrosis, and that silencing of SHP-2 gene in myeloid cells may protect renal from inflammatory damage and prevent renal fibrosis after renal injury.

A matched-pair comparison of single plus one port versus standard extraperitoneal laparoscopic radical prostatectomy by a single urologist.

We conducted this study to report on our initial experience and assess the safety, feasibility, and efficacy of extraperitoneal single plus one port laparoscopic radical prostatectomy (SPOPL-RP), and determine whether it shows any objective advantage over standard laparoscopic radical prostatectomy. From June 2009 to September 2011, 15 extraperitoneal SPOPL-RPs were performed through a 2-3-cm subumbilical longitudinal incision and another 5-mm trocar placed at the McBurney point. This cohort was compared with 37 contemporary patients who underwent standard extraperitoneal laparoscopic radical prostatectomy performed by the same urologist. Peri- and postoperative outcomes, including continence, potency, and scar length, were statistically analyzed. The two groups were comparable with respect to patient demographics, estimated blood loss, drainage time, duration of catheterization, catheterization rate >14 days, complication rate, postoperative hospitalization, and postoperative functional and oncologic outcomes (p > 0.05). The SPOPL-RP procedures had a longer mean operative time (170.1 minutes vs. 139.5 minutes, p = 0.005), but with fewer patients requiring analgesics (20% vs. 54.1%, p = 0.038) and earlier resumption of oral intake (20.7 hours vs. 26.8 hours, p = 0.037). The mean scar length in the SPOPL-RP group was much smaller (3.4 cm vs. 5.8 cm, p = 0.000) owing to the significant reduction of the skin incision. The peri- and postoperative outcomes of SPOPL-RP for low-risk prostate cancer are comparable to those with the standard laparoscopic approach. In addition, SPOPL-RP provides better postoperative pain control, faster recovery of bowel function, and smaller scar length than standard laparoscopy, albeit with a longer operative time.

Holmium laser versus conventional transurethral resection of the bladder tumor.

BACKGROUND: Transurethral resection of the bladder tumor (TURBT) remains the gold standard for non-muscle-invasive bladder cancer (NMIBC). Laser techniques have been widely used in urology. This analysis aimed to assess the safety and efficacy of holmium resection of the bladder tumor (HoLRBT) vs. TURBT. METHODS: A systemic search of MEDLINE, Embase, Web of Science, and The Cochrane Library as well as manual bibliography searches were performed to identify the relevant studies. The pooled estimates of operation time, obturator nerve reflex rate, bladder perforation rate, bladder irrigation rate, catheterization time, hospital stay, and one- and two-year recurrence free survivals were calculated. RESULTS: Five studies were enrolled into our meta-analysis. No significant difference was observed in the operation time between groups (weighted mean difference (WMD) 1.01, 95% confidential interval (95% CI) -3.52 - 5.54, P = 0.66). The significant difference in the obturator nerve reflex (OR 0.05, 95% CI 0.01 - 0.04, P = 0.004), bladder perforation (OR 0.14, 95% CI 0.03 - 0.61, P = 0.009), bladder irrigation (OR 0.13, 95% CI 0.04 - 0.45, P = 0.001), catheterization time (WMD -0.96, 95% CI -1.11 to -0.82, P < 0.00001), and hospital stay (WMD -1.46, 95% CI -1.65 to -1.27, P < 0.00001) showed advantages of HoLRBT over TURBT. The 2-year recurrence free survival rate favors the HoLRBT group (OR 1.46, 95% CI 1.02 - 2.11, P = 0.04). CONCLUSIONS: As a promising technique, HoLRBT is safe and efficient, and showed several advantages over TURBT. HoLRBT can be used as an alternative procedure for TURBT in terms of low-grade papillary urothelial carcinoma or low-grade early TNM-stage urothelial carcinoma.

Transperitoneal laparoscopic excision of primary seminal vesicle benign tumors: surgical techniques and follow-up outcomes.

OBJECTIVE: To assess the feasibility, safety, and efficacy of transperitoneal laparoscopic excision of primary seminal vesicle benign tumors (SVBTs) and summarize our experience with surgical techniques and follow-up outcomes of this rare condition. METHODS: This study included 6 patients who underwent transperitoneal laparoscopic excision of primary SVBTs between June 2005 and April 2011. A 5-port transperitoneal approach was used. The ipsilateral vas deferens was identified in the upper bulge of the retrovesical peritoneal reflection through a transverse approach and was dissected inwardly and used as a guide to the seminal vesicle tumor. Endoscopic Hem-o-lok clips (Teleflex Medical) were applied to control the vascular supply to the tumor base. With the contralateral vas deferens and seminal vesicle preserved, the tumor was removed together with the vas deferens and the adjoining ipsilateral seminal vesicle. The surgical procedures were successful in all 6 patients, without conversion to open surgery. The mean duration of surgery was 70 ± 16 minutes (range, 50-100 minutes), with unremarkable blood loss of less than 50 mL. The mean postoperative hospital length of stay was 5.2 ± 1.6 days (range, 4-8 days). No intra- or postoperative complications occurred. During a mean follow-up period of 42 ± 24 months (range, 12-82 months), all patients remained asymptomatic, with preserved function as reported by the patient, and there was no evidence of recurrence. CONCLUSION: Our study demonstrated that transperitoneal laparoscopic excision of primary SVBTs is a viable option for minimally invasive treatment of SVBT.