Verapamil inhibits ureteral scar formation by regulating CaMK II-mediated Smad pathway.

Verapamil is reported to prevent scar formation. However, whether verapamil is involved in the ureteral stricture scar and the underlying mechanism need further investigation. Fibroblasts were isolated from ureteral scar tissues. TGF-ß1 stimulation was used to induce fibrosis of fibroblasts. Inhibition of CaMK II was achieved by shRNA transfection. CCK-8 was performed to evaluate cell viability. qRT-PCR was applied to determine the level of mRNA while western blotting was used to determine the level of proteins. Immunofluorescence was used to detect the level of vimentin, collagen I and collagen III. Primary fibroblasts was successfully isolated from ureteral scar tissues. TGF-ß1 stimulation was capable to induce collagen production and fibrosis in primary fibroblasts while inhibition of CaMK II attenuate collagen production. Overexpression of wild type CaMK II lead to further increase of collagen production upon TGF-ß1 stimulation while the mutated CaMK II did not exert this promotion. Treatment of verapamil inhibits TGF-ß1 induced collagen production via inhibiting CaMK II. In present study, we revealed a vital role of Verapamil and CaMK II in the formation of ureteral scar. Verapamil inhibited TGF-ß1 induced collagen fiber formation by regulating CaMK II. Our finding might provide new insight into mechanism of prevention and treatment of ureteral scar.

Two-stage laparoscopic repair of two-level ureteral strictures: our experience of 8 patients.

PURPOSE: To evaluate the feasibility and effectiveness of two-stage laparoscopic repair for two-level ureteral strictures. MATERIALS AND METHODS: From October 2010 to January 2017, 8 patients with two-level ureteral strictures, which were located in upper and lower ureter, received two-stage laparoscopic repair in our institution. Laparoscopic ureteroureterostomy was conducted for the upper ureteral strictures in first stage and 8 weeks later laparoscopicureterovesical reimplantation was performed for lower stricture after the patency of upper lesion was confirmed by antegrade ureteropyelography. The kidney was drained by a nephrostomy tube during the interval period of two operations. RESULT: All the operations were performed successfully without intraoperative complications except one patient converted to open surgery during second-stage operation. For first-stage surgery, mean operating time was 120.88 ± 16.88 min, mean blood loss was 89.38 ± 13.74 mL, and mean duration of postoperative hospitalization was 3.63± 0.74 days. While in second-stage surgery, mean operating time took 125.25 ± 17.00 min, mean blood loss was 65.63 ± 10.16 mL, and mean duration of postoperative hospitalization was 3.62 ± 1.41 days.. On ureteropyelography 10 weeks after second-stage surgery, the contrast medium flowed from kidney down into bladder unrestrictedly and the patency of entire ureter was restored in all patients. During the follow-up, one female was observed kidney atrophy with ureteral calculus formed on the lesion side, and was successfully treated by ureteroscopiclithotripsy. No sign of stricture recurrence was found on other patients. CONCLUSION: Two-stage laparoscopic repair is a feasible and effective treatment for two-level ureteral strictures.But its indication is relatively narrow and confined to ureteral strictures located in two sites with sufficient intervaldistance and minor stricture length.

Diagnosis and management of testicular rupture after blunt scrotal trauma: a literature review.

Testicular rupture, one of the most common complications in blunt scrotal trauma, is the rupture of tunica albuginea and extrusion of seminiferous tubules. Testicular rupture is more inclined to young men, and injury mechanisms are associated with sports and motor accidents. After history taking and essential physical examination, scrotal ultrasound is the first-line auxiliary examination. MRI is also one of the vital complementary examinations to evaluate testicular rupture after blunt scrotal trauma. Surgical exploration and repair may be necessary when the diagnosis of testicular rupture is definite or suspicious. Postoperative follow-up is to monitor the relief of local symptoms and changes of testicular functions. This review sums up the literatures about testicular rupture after blunt scrotal trauma in recent 16 years and also refers some new advantages and perspectives on diagnosis and management of testicular rupture.

Downregulation of VEGFA inhibits proliferation, promotes apoptosis, and suppresses migration and invasion of renal clear cell carcinoma.

OBJECTIVE: The aim of this study was to investigate the effects of vascular endothelial growth factor A (VEGFA) on cell proliferation, apoptosis, migration, and invasion in renal clear cell carcinoma (RCCC). METHODS: Between June 2012 and June 2015, RCCC tissues were obtained for the experimental group, and RCCC adjacent tumor-free kidney parenchyma tissues were obtained for the control group. VEGFA mRNA and protein expressions and phosphoinositide 3-kinase, serine/threonine-specific protein kinase (AKT), and phosphorylated-AKT protein expressions were detected. The chemically synthesized specific siRNA using RNA interference technology was used to inhibit VEGFA gene expression in human RCCC 786-O cells. The negative control (NC) group was transfected with NC sequence, and the blank group was transfected with no sequence. Flow cytometry, scratch test, and cell-penetrating experiment were used to detect cell proliferation, apoptosis, migration, and invasion of 786-O cells. RESULTS: Positive expression of VEGFA protein was 60.62% in RCCC tissue and 18.34% in adjacent tissue with statistically significant difference (P<0.001). VEGFA protein and mRNA expressions were higher in RCCC tissue than those in adjacent tissue (both P<0.01). VEGF expression in RCCC tissue was associated with Fuhrman grading and American Joint Committee on Cancer staging (both P<0.05). After RCCC 786-O cells transfecting the VEGFA siRNA, the VEGFA mRNA and protein expressions and phosphoinositide 3-kinase and phosphorylated-AKT protein expressions were significantly decreased, cell proliferation was remarkably inhibited, cell apoptotic ratio was obviously increased, and migration distance and invasive cell number were markedly decreased compared to those in the NC group and the blank group (all P<0.05). CONCLUSION: Inhibition of VEGFA inhibited proliferation, promoted apoptosis, and suppressed migration and invasion of RCCC 786-O cells. VEGF has a potential role in diagnosis and therapy of RCCC.