180-W GreenLight laser photoselective vaporization with multiple triamcinolone acetonide injections for the treatment of bladder neck contractures.

Bladder neck contracture (BNC), one of the most challenging complications after transurethral resection of the prostate (TURP) and photoselective vaporization of the prostate (PVP), lacks effective treatment. In the present study, our experience in treating BNC using GreenLight laser vaporization with triamcinolone acetonide (TA) injections was shared. This is a retrospective cohort study that included 46 patients with BNC after TURP and PVP in our center. GreenLight laser surgeries (180 W) were carried out and TA was administrated simultaneously. TA injections were repeated every week for three times after surgeries. The perioperative and postoperative parameters were reviewed and compared. Bladder neck tissues were examined by immunohistochemical staining to explore the expressions of collagen I, matrix metalloproteinase-3 (MMP-3), and transforming growth factor-ß (TGF-ß) after treatments. The chief complaint symptoms of all patients were significantly relieved after our treatments. None of them showed BNC recurrence during the follow-up. Complications were rare and mild. Postoperative assessments including maximal urinary flow rate (P < 0.01), International Prostate Symptom Score (P < 0.01), quality of life index (P < 0.01), and post-void residual volume (P < 0.001) were significantly better than baseline values, respectively. Immunohistochemical staining showed significantly lower expressions of collagen I (P < 0.001), MMP-3 (P < 0.001), and TGF-ß (P < 0.001) after treatments. In conclusion, 180-W GreenLight laser with repeated TA injections demonstrated the safety and long-term efficacy in treating BNC, by inhibiting the expressions of fibrotic factors. Our procedure was a promising treatment for BNC after PVP and TURP.

miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4.

BACKGROUND: miR-148-3p and miR-152-3p as the tumor suppressors have been reported in various cancer types. Our study is aimed to discuss the synergistic effect of miR-148-3p and miR-152-3p in prostate cancer (PCa). METHODS: Bioinformatics algorithm and luciferase reporter assays were used to verify whether miR-148-3p and 152-3p could bind with the 3'-untranslated region (3'-UTR) of Kruppel-like factor 4 (KLF4). PCa cell growth in vivo was analyzed using the mouse xenograft tumor model. RESULTS: miR-148-3p and miR-152-3p were reduced in PCa tumor tissues. Moreover, the protein expression of KLF4 was increased in PCa tissues. The 3'-UTR of KLF4 contained the conserved binding sites with miR-148-3p and miR-152-3p. The mimics or inhibitors of miR-148-3p and/or miR-152-3p could downregulated or upregulated KLF4 expression, respectively. miR-148-3p and miR-152-3p-induced PCa cell growth inhibition were observed both in vivo and in vitro. KLF4 overexpression had the ability to neutralize the antitumor effect of miR-148-3p/152-3p in vivo and in vitro. CONCLUSION: miR-148-3p/152-3p family could serve as tumor suppressors in PCa via repressing KLF4.

Abdominal cocoon with bilateral cryptorchidism and seminoma in the right testis: a case report and review of literature.

BACKGROUND: Abdominal cocoon is a rare peritoneal lesion and is difficult to diagnose because of its lack of special clinical manifestations. Until now, there is no case report of abdominal cocoon combined with cryptorchidism and seminoma. CASE PRESENTATION: A case of abdominal cocoon with cryptorchidism and seminoma was diagnosed and treated in our hospital. The patient had no symptoms except occasional abdominal pain. He underwent laparoscopy because of bilateral cryptorchidism and seminoma in the right testis. During the surgery, he was diagnosed with abdominal cocoon due to the thick fibrous tissues which was tightly adhered and encased part of intestine like a cocoon. Enterolysis and bilateral cryptochiectomy were performed after the diagnosis and nutritional and symptomatic support was provided after the surgery. The patient recovered well and was discharged soon. The postoperative pathological examination confirmed the presence of bilateral cryptorchidism and seminoma in the patient's right testis. CONCLUSION: There are only a handful of cases where a patient has both abdominal cocoon and cryptorchidism. Since the etiologies of both diseases remain unknown, further research is required to investigate effective diagnosis and treatment for the diseases and explore the potential connection between the two diseases.

p53ß: a new prognostic marker for patients with clear-cell renal cell carcinoma from 5.3 years of median follow-up.

We previously reported six different p53 isoforms in renal cell carcinoma (RCC). In the present study, influences of p53ß on recurrence-free survival (RFS) and overall survival (OS) were evaluated. Patients diagnosed with RCC in our center were into this study. mRNA expressions of p53 isoforms (p53α, p53ß, p53γ) in tumors were determined by RT-PCR and real-time PCR. Functional yeast-based assay was performed to analyze p53 mutational status. p53ß transfected 786-O and CAKi-1 cells were cultured to examine expressions of B-cell lymphoma 2-associated X protein (bax) and caspase-3, and ratios of apoptosis. After surgeries, all patients were followed up at programmed intervals. 266 patients were analyzed in this study. Median follow-up time was 5.3 years. RT-PCR (r = -0.72, P = 0.016) and real-time PCR (r = -0.65, P = 0.033) both showed only p53ß expressed higher level in lower tumor stage versus higher stage. p53 wild-type and p53 mutation had comparable RFS (P = 0.361) and OS (P = 0.218), respectively. Kaplan-Meier analysis showed high p53ß expression was associated with significantly improved RFS and OS, regardless of p53 mutational status. High p53ß expression indicated better RFS [hazard ratio (HR) 2.599, 95% confidence interval (CI) 1.472-4.551, P = 0.038] and OS (HR 2.604, 95% CI 1.453-4.824, P = 0.031). p53ß transfected 786-O and CAKi-1 cells expressed significantly higher level of bax and caspase-3, and had higher ratios of apoptosis than untransfected cells. Taken together, higher level of p53ß predict better prognosis in patients with RCC through enhancing apoptosis in tumors.

Long noncoding RNA SNHG16 contributes to the development of bladder cancer via regulating miR-98/STAT3/Wnt/ß-catenin pathway axis.

This study aimed to investigate the role and the possible mechanism of the long noncoding small nucleolar RNA host gene 16 (SNHG16) in bladder cancer development. The expression of SNHG16 in the tumor tissues and plasma of patients with bladder cancer as well as bladder cancer cell lines was detected. T24 cells were then transfected with sh-SNHG16 to further investigate the effects of suppression of SNHG16 on T24 cell proliferation, apoptosis, migration, and invasion. In addition, the regulatory relationships between SNHG16 and miR-98 as well as the target of miR-98 were explored. Besides, the association between SNHG16 and the Wnt/ß-catenin pathway was further elucidated. The SNHG16 expression was upregulated in the tumor tissues and plasma of patients with bladder cancer, as well as bladder cancer cells. Suppression of SNHG16 inhibited T24 cell proliferation, promoted apoptosis, and suppressed migration and invasion in vitro. In addition, SNHG16 negatively regulated miR-98 expression and regulated the malignant behaviors of T24 cells through sponging miR-98. Moreover, signal transducer and activator of transcription 3 (STAT3) was identified as a functional target of miR-98, and miR-98 regulated the malignant behaviors of bladder cancer cells by targeting STAT3. Besides, suppression of SNHG16 inhibited the activation of the Wnt/ß-catenin pathway, which was further regulated by miR-98 and STAT3, indicating that the effects of SNHG16/miR-98/STAT3 on T24 cells were achieved through the Wnt/ß-catenin pathway. Our findings reveal that long noncoding RNAs SNHG16 is upregulated in bladder cancer and contributes to the development of bladder cancer possibly via regulating the miR-98/STAT3/Wnt/ß-catenin pathway axis. The SNHG16/miR-98/STAT3/Wnt/ß-catenin pathway axis may provide a new strategy for bladder cancer treatment.

LncRNA CCAT1 inhibits cell apoptosis of renal cell carcinoma through up-regulation of Livin protein.

This study was to investigate the involvement of long non-coding RNA (lncRNA) colon cancer-associated transcript-1 (CCAT1) in renal cell carcinoma (RCC) and to further uncover its underlying mechanism. In this study, the expression of CCAT1 and Livin of RCC tissues or cells was determined using qRT-PCR (quantitative real-time PCR) and western blot, respectively. RNA pulldown and RIP (RNA-Binding Protein Immunoprecipitation) assays were performed to examine the sequence interaction between CCAT1 and Livin. The viability and apoptosis of RCC cells was assessed by MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and TUNEL (TdT-mediated dUTP nick end labeling) assays, respectively. Mice of tumor animal models were established to observe the effect of CCAT1 on RCC tumor growth. The relative expression of CCAT1 in RCC tissues and cell lines was obviously higher than that of the control. CCAT1 knockdown could reduce cell viability and increase the apoptosis of RCC cells in vitro. Furthermore, Livin was significantly inhibited by CCAT1 silencing; RNA pulldown and RIP assays showed that CCAT1 was physically associated with Livin protein. Moreover, Livin overexpression not only significantly inhibited RCC cell apoptosis and increased cell viability, but completely reversed the si-CCAT1-mediated repression of cell viability. More importantly, CCAT1 silencing could inhibit the growth of RCC in vivo that was accompanied by the reduction of Livin in RCC tissues. CCAT1 inhibits RCC cell apoptosis and increases cell viability through up-regulation of Livin.

Defocused low-energy shock wave activates adipose tissue-derived stem cells in vitro via multiple signaling pathways.

BACKGROUND AIMS: We found defocused low-energy shock wave (DLSW) could be applied in regenerative medicine by activating mesenchymal stromal cells. However, the possible signaling pathways that participated in this process remain unknown. In the present study, DLSW was applied in cultured rat adipose tissue-derived stem cells (ADSCs) to explore its effect on ADSCs and the activated signaling pathways. METHODS: After treating with DLSW, the cellular morphology and cytoskeleton of ADSCs were observed. The secretions of ADSCs were detected. The expressions of ADSC surface antigens were analyzed using flow cytometry. The expressions of proliferating cell nuclear antigen and Ki67 were analyzed using western blot. The expression of CXCR2 and the migrations of ADSCs in vitro and in vivo were detected. The phosphorylation of selected signaling pathways with or without inhibitors was also detected. RESULTS: DLSW did not change the morphology and phenotype of ADSCs, and could promote the secretion, proliferation and migration of ADSCs. The phosphorylation levels were significantly higher in mitogen-activated protein kinases (MAPK) pathway, phosphoinositide 3-kinase (PI-3K)/AKT pathway and nuclear factor-kappa B (NF-κB) signaling pathway but not in Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Furthermore, ADSCs were not activated by DLSW after adding the inhibitors of these pathways simultaneously. CONCLUSIONS: Our results demonstrated for the first time that DLSW could activate ADSCs through MAPK, PI-3K/AKT and NF-κB signaling pathways. Combination of DLSW and agonists targeting these pathways might improve the efficacy of ADSCs in regenerative medicine in the future.

Gastrodin Attenuates Cognitive Deficits Induced by 3,3'-Iminodipropionitrile.

3,3'-Iminodipropionitrile (IDPN), one of the nitrile derivatives, can induce persistent neurotoxicity, and therefore cause dyskinesia and cognitive impairments. Gastrodin, a main bioactive ingredient of Gastrodia elata Blume, is shown to greatly improve cognitive function. The aim of this study was to further determine whether administration of gastrodin can ameliorate IDPN-induced cognitive deficits in the Morris water maze (MWM) and novel object recognition (NOR) task, and to explore the underlying mechanisms. Results showed that exposure to IDPN (100 mg/kg/day, for 8 days) significantly impaired spatial and object recognition memory and that repeated treatment with gastrodin (150 mg/kg/day, for 6 weeks) could effectively alleviate the IDPN-induced cognitive impairments as indicated by increased spatial memory and discrimination ratio in the MWM and NOR tests. Gastrodin treatment also reverted IDPN-induced decreases of γ-aminobutyric acid (GABA) levels and increases of a2 GABAA receptor protein expression in the prefrontal cortex and hippocampus of IDPN-treated rats. These results suggest that gastrodin treatment may provide a novel pharmacological strategy for IDPN-induced cognitive deficits, which was mediated, at least in part, by normalizing the GABAergic system.

Green-light laser en bloc resection for primary non-muscle-invasive bladder tumor versus transurethral electroresection: A prospective, nonrandomized two-center trial with 36-month follow-up.

OBJECTIVES: To evaluate the safety and efficacy of LBO laser en bloc resection compared with transurethral electroresection (TURBT) for the treatment of primary non-muscle-invasive bladder tumors. METHODS: From September 2010 to February 2012, a prospective, nonrandomized two-center trial was performed. A total of 158 patients (83 underwent laser resection and 75 TURBT) were included in the present study. The preoperative, intraoperative, and postoperative clinical characteristics were recorded and compared in the two groups. RESULTS: There were no differences with the preoperative characteristics between the patients in the two groups. The mean operative time was 21.46 ± 10.42 minutes for laser resection and 27.47 ± 15.30 minutes for TURBT (P = 0.004). LBO laser group was also associated with less hemoglobin decrease compared with TURBT group (0.87 ± 0.28 g/ml vs. 1.00 ± 0.33 g/ml, P = 0.009). Obturator nerve reflection was absent during laser resection, whereas was observed in nine patients during TURBT (P = 0.001). Two patients in the TURBT group suffered bladder perforation. Three patients in TURBT group and one patient in LBO laser group experienced urethral stricture. The recurrence-free survival rate did not differ significantly between two groups after 36 months follow-up. CONCLUSIONS: The results of our trial have shown that LBO laser en bloc resection is feasible, safe, and effective alternative for the treatment of primary non-muscle-invasive bladder tumors. Besides, it can provide intact specimen for the pathologic diagnosis. Lasers Surg. Med. 48:859-865, 2016. © 2016 Wiley Periodicals, Inc.

A comparison of incidences of bladder neck contracture of 80- versus 180-W GreenLight laser photoselective vaporization of benign prostatic hyperplasia.

Bladder neck contracture (BNC) after GreenLight laser photoselective vaporization (PVP) of benign prostatic hyperplasia is a common complication. In the present study, data of patients received 80 or 180 W PVP were collected. Perioperative parameters, including applied energy, irradiation time, catheter removal time, and hospital stay, were recorded. Postoperative parameters, including maximum urinary flow rate, International Prostate Symptom Score, post-void residual volume, and incidences of BNC, were recorded at 3 and 12 months after operations. Bladder neck tissues were taken at 3 months after operations for immunohistochemical staining and western blot analysis to examine the expressions of collagen I, matrix metalloproteinase-3 (MMP-3), and transforming growth factor-ß (TGF-ß). Sample size of patients was calculated with a power of 80 %. Chi-square test and one-way analysis of variance were performed as statistical methods. Three hundred twenty-six patients who received potassium titanyl phosphate (KTP) laser and 256 who received X-ray photoelectron spectroscopy (XPS) laser entered into the study. Perioperative parameters were comparable, except for shorter irradiation time in 180 W group (P = 0.032). Postoperative parameters were also similar, except for higher incidence of BNC in 80 W group at 3 months after operations (P = 0.022). Immunohistochemical staining and western blot analysis showed higher expressions of collagen I, MMP-3, and TGF-ß in 80 W group than in 180 W group. In conclusion, 80 W GreenLight laser showed a comparable efficacy with 180-W laser in PVP but showed a higher incidence of BNC in short term, which might be the result of up-regulated fibrotic factors in bladder neck triggered by lasers.

[Focusing on MRI-suspected lesions in targeted transrectal prostate biopsy guided by MRI-TRUS fusion imaging for the diagnosis of prostate cancer].

OBJECTIVE: To improve the accuracy of prostate cancer (PCa) detection by focusing biopsy on the suspected lesion manifested by MRI with the total number of biopsy cores relatively unchanged. METHODS: A prospective randomized analysis was performed on 262 cases of suspected PCa detected by multi-parametric MRI (mp-MRI), each with a single suspected lesion with 10 µg/L≤ PSA <20 µg/L. All the patients underwent targeted transrectal prostate biopsy guided by fusion imaging of MRI with transrectal ultrasonography (TRUS), using the 6X+6 strategy (6 cores in the suspected region and another 6 in the systematic prostate) for 134 cases and the traditional 12+2X method (12 cores in the systematic prostate and 2 in the suspected region) for the other 128. Comparisons were made between the two methods in the PCa detection rate in the cases of suspected lesion, total PCa detection rate, incidence of post-biopsy complications, and Gleason scores. Analyses were performed on the prostate imaging reporting and data system (PI-RADS) score, location, transverse section, and diameter of the suspected lesion. RESULTS: Both the total PCa detection rate and that in the cases of suspected lesion were significantly higher in the 6X+6 (44.8% and 37.3%) than in the 12+2X group (37.5% and 27.3%) (P<0.05). MRI showed that the suspected lesions were mostly (45%) located in the middle part of the prostate, the mean area of the transverse section was (0.48±0.11) cm2, and the mean diameter of the tumor was (8.51±2.21) mm. The results of biopsy showed that low-grade tumors (Gleason 3+3=6) accounted for 68% in the 6X+6 group and 71% in the 12+2X group. No statistically significant differences were found between the two groups in the incidence rate of post-biopsy complications. CONCLUSIONS: Compared with the traditional 12+2X method, for the suspected lesion manifested by mp-MRI, focusing biopsy on the suspected region with the 6X+6 strategy can achieve a higher PCa detection rate without increasing the incidence of complications.

Folliculin deficient renal cancer cells show higher radiosensitivity through autophagic cell death.

PURPOSE: Mutations in the FLCN gene are responsible for fibrofolliculoma, pulmonary and renal cysts, and renal cell carcinoma in patients with Birt-Hogg-Dubé syndrome. To explore therapeutic approaches to renal cell carcinoma in patients with Birt-Hogg-Dubé syndrome we investigated the anticancer effects of irradiation on folliculin deficient renal cancer cells. MATERIALS AND METHODS: Folliculin deficient (UOK257 and ACHN-5968) and folliculin expressing (UOK257-2 and ACHN-sc) cell lines were used in this study. Clonogenic assays were used to determine the radiosensitivity of folliculin deficient and expressing renal cell carcinoma cells. Apoptosis was detected in these cells by DAPI and TUNEL assays after irradiation. Monodansylcadaverine analysis, GFP-LC3 assay and Western blot were performed to monitor the autophagic process. RESULTS: Folliculin deficient cells were more sensitive to irradiation than their folliculin expressing counterparts. The enhanced effects of irradiation on folliculin deficient cells were mediated by increased autophagy but not by apoptosis. An increased Beclin 1 protein level and an activated mitogen-activated protein kinase pathway were identified as the key regulators of increased autophagy in these folliculin deficient cells. Inhibiting autophagy with 3-methyladenine or beclin 1 siRNA obviously increased radioresistance in folliculin deficient cells. Moreover, irradiation combined with autophagic inducer rapamycin significantly increased autophagy and radiosensitivity in folliculin deficient renal cell carcinoma cells. CONCLUSIONS: Findings suggest that folliculin deficient renal cell carcinoma cells are highly sensitive to irradiation due to increased autophagic cell death, unlike other types of renal cell carcinoma. Irradiation plus autophagy inducers, eg rapamycin, might be a potentially more effective therapeutic approach to folliculin deficient renal cell carcinoma.

Metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through mTOR/S6K1-mediated downregulation of c-FLIP.

Metformin, an oral antidiabetic agent, has been reported to potentiate chemotherapeutic-induced cytotoxicity. In this study, we investigated the effects and molecular mechanisms of metformin in sensitizing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human bladder cancer cells. Metformin alone did not induce apoptosis, but markedly potentiated TRAIL-induced apoptosis in 253J and RT4 bladder cancer cells. To elucidate the underlying mechanism, we examined the modulatory effects of metformin on the key components of the TRAIL signaling pathway and found that metformin did not alter the expression levels of death receptor 4 (DR4) and death receptor 5 (DR5), but significantly reduced the cellular Fas-associated death domain (FADD)-like interleukin-1ß-converting enzyme (FLICE) inhibitory protein (c-FLIP) levels, contributing toward the sensitization to TRAIL. Further experiments showed that metformin did not affect the mRNA level, proteasomal degradation, and protein stability of c-FLIPL. However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway. In addition, AMP-activated protein kinase (AMPK) inhibitor compound C did not prevent the inhibitory effects of metformin on the mTOR/S6K1 pathway and metformin-mediated sensitization to TRAIL. Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.

A creative therapy in treating cavernous hemangioma of penis with copper wire.

INTRODUCTION: Cavernous hemangiomas of penis are rare benign lesions infrequently described in the literature. No completely satisfactory treatment has been found to correct the cosmetic deformities especially the extensive hemangiomas of corpus penis. AIM: In light of the promising application of copper wire/needle in vascular malformations, we began a clinical study to investigate the safety, feasibility, and cosmetic effect of copper wire therapy in treating cavernous hemangioma of penis. METHODS: Seven patients ranging in age from 12 to 32 years with penile cavernous hemangiomas entered our study from 2005 to 2011. All patients received treatments with percutaneous copper wires. MAIN OUTCOME MEASURES: Perioperative data including mean operation time, estimated blood loss, length of copper wire retention, and length of hospital stay were analyzed. All possible complications were noted, and cosmetic result was evaluated. Patients were followed up after discharge from the hospital. RESULTS: All operations were successful, and no obvious complications were observed. The patients were satisfied with the aesthetic results. Follow-up time ranged from 1 to 5 years. Recurrence was discovered in a patient with the largest lesion of corpus penis 2 months after the treatment. Secondary procedure was carried out with the same technique, and no lesions were found later. CONCLUSIONS: The shortage of studies on this topic prevented us from defining a therapeutic reference standard. The results of our study confirmed that copper wire therapy was a simple, safe, and useful option for penile cavernous hemangioma.

Evodiamine induces apoptosis and enhances TRAIL-induced apoptosis in human bladder cancer cells through mTOR/S6K1-mediated downregulation of Mcl-1.

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), either alone or in combination with other anti-cancer agents, has been considered as a new strategy for anti-cancer therapy. In this study, we demonstrated that evodiamine, a quinolone alkaloid isolated from the fruit of Evodia fructus, induced apoptosis and enhanced TRAIL-induced apoptosis in human bladder cancer cells. To elucidate the underlying mechanism, we found that evodiamine significantly reduced the protein levels of Mcl-1 in 253J and T24 bladder cancer cells, and overexpression of this molecule attenuated the apoptosis induced by evodiamine alone, or in combination with TRAIL. Further experiments revealed that evodiamine did not affect the mRNA level, proteasomal degradation and protein stability of Mcl-1. On the other hand, evodiamine inhibited the mTOR/S6K1 pathway, which usually regulates protein translation; moreover, knockdown of S6K1 with small interfering RNA (siRNA) effectively reduced Mcl-1 levels, indicating evodiamine downregulates c-FLIP through inhibition of mTOR/S6K1 pathway. Taken together, our results indicate that evodiamine induces apoptosis and enhances TRAIL-induced apoptosis possibly through mTOR/S6K1-mediated downregulation of Mcl-1; furthermore, these findings provide a rationale for the combined application of evodiamine with TRAIL in the treatment of bladder cancer.

Activation of bone marrow-derived mesenchymal stromal cells-a new mechanism of defocused low-energy shock wave in regenerative medicine.

BACKGROUND AIMS: Defocused low-energy shock wave (DLSW) therapy has shown effectiveness in regenerative medicine. The mechanism of action was mainly focused on the pathophysiological improvement at the wound tissues. In this study, the activation of stem cells treated by DLSW was first examined as an important pathway during the healing process. METHODS: Cultured rat bone marrow-derived mesenchymal stromal cells (BMSC) were treated by DLSW before each passage. The untreated BMSC served as a control. The secretions of vascular endothelial growth factor (VEGF) and CXC ligand 5 (CXCL5) were tested by means of enzyme-linked immunoassay. Flow cytometry was performed to analyze the BMSC (passage 4) surface antigen expressions (CD166, CD44 and CD34). The expressions of proliferating cell nuclear antigen and Ki67 were analyzed by means of Western blot. The healing abilities of conditioned media of shocked and unshocked BMSC were examined by Matrigel-based capillary-like tube formation assay and rat major pelvic ganglia culture test. RESULTS: The shocked BMSC secreted more VEGF and CXCL5 than did those of unshocked BMSC. The expressions of CD166, CD44 and CD34 showed no significant differences (P > 0.05) between the shocked and unshocked BMSC. The shocked BMSC demonstrated higher expressions of proliferating cell nuclear antigen (P < 0.01) and Ki67 (P < 0.01) than did those of unshocked BMSC. The shocked BMSC conditioned medium showed higher ability to enhance the growth of major pelvic ganglia neurites (P < 0.05) and Matrigel-based endothelial tube-like formation (P < 0.05). CONCLUSIONS: DLSW did not interfere with the expressions of cell surface markers. DLSW enhanced the secretion and proliferation of BMSC and promoted angiogenesis and nerve regeneration in vitro.

The antidiabetic drug metformin inhibits the proliferation of bladder cancer cells in vitro and in vivo.

Recent studies suggest that metformin, a widely used antidiabetic agent, may reduce cancer risk and improve prognosis of certain malignancies. However, the mechanisms for the anti-cancer effects of metformin remain uncertain. In this study, we investigated the effects of metformin on human bladder cancer cells and the underlying mechanisms. Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of p21waf-1. Further experiments revealed that metformin activated AMP-activated protein kinase (AMPK) and suppressed mammalian target of rapamycin (mTOR), the central regulator of protein synthesis and cell growth. Moreover, daily treatment of metformin led to a substantial inhibition of tumor growth in a xenograft model with concomitant decrease in the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and p-mTOR. The in vitro and in vivo results demonstrate that metformin efficiently suppresses the proliferation of bladder cancer cells and suggest that metformin may be a potential therapeutic agent for the treatment of bladder cancer.

High-power green-light laser endoscopic submucosal dissection for non-muscle-invasive bladder cancer: A technical improvement and its initial application.

Background: The technique of laser en bloc resection of bladder tumor (ERBT) has been a valuable alternative technique to transurethral resection of bladder tumor (TURBT). However, the combination of laser ERBT and endoscopic submucosal dissection (ESD) technique has not been well studied. Here, a novel technique integrating a high-power green-light laser with ESD was presented. This study aimed to evaluate the safety and efficacy of high-power green-light laser endoscopic submucosal dissection (HPL-ESD) for the treatment of primary non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: From January 2015 to December 2018, a total of 56 patients with NMIBC underwent HPL-ESD. All tumors were transurethral en bloc resected in the ESD technique. Perioperative clinical data were retrospectively collected and analyzed. Results: All operations were safely performed by the technique of HPL-ESD without blood transfusion. The mean tumor diameter was 2.04 ± 0.65 cm, ranging from 0.5 to 3.5 cm. The mean operative time was 28.39 ± 16.04 min. The average serum hemoglobin decrease was 0.88 ± 0.54 g/dL. The mean postoperative catheterization time was 2.88 ± 0.94 days. The pathologic stages included pTa (32 cases), and pT1 (24 cases). Double-J stent indwelling was not performed for four patients whose tumors were adjacent to the ureteral orifice and no postoperative hydronephrosis was observed. Only one case of ectopic bladder tumor recurred due to irregular bladder irrigation during the 36-month follow-up. Conclusion: HPL-ESD is a safe and effective alternative for the treatment of primary NMIBCs, especially for tumors adjacent to the ureteral orifice.

The incidence and clinical features of acute kidney injury secondary to ureteral calculi.

The aim of this study is to evaluate the incidence and clinical features of acute kidney injury (AKI) secondary to ureteral calculi. Between February 2002 and December 2009, the prevalence of AKI was 0.72% in our series of 2,073 cases of ureteral stones. The AKI patients received ureteroscopy or percutaneous nephrostomy as the primary treatment. The most popular symptom was significant decrease in urine output (75%, 12/16). Five cases (33.3%) were caused by bilateral ureteral stones, and 76.19% of the stones were located in the upper ureter, the mean size of single stone was 1.35 ± 0.38 cm. The serum creatinine before treatment was 514.34 ± 267.04 µmol/L and the blood urea nitrogen before treatment was 21.31 ± 10.24 mmol/L. 46.67% of the patients had a functional or anatomical solitary kidney unit. Our study suggests that risk factors for developing AKI in ureteral stone patients are bigger sized stones, ureteral stones in patients with only one functioning kidney or pre-existing kidney disease, and bilateral ureteral stones. Early effective drainage in these cases could decrease the risk developing AKI secondary to ureteral calculi.

The retrospective study of perioperative application of dexamethasone and furosemide for postoperative anti-inflammation in patients undergoing percutaneous nephrolithotomy.

OBJECTIVES: To investigate whether the perioperatively combined application of dexamethasone and furosemide could alleviate the inflammation in patients undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: 147 patients undergoing PCNL between November 2018 and October 2019 were enrolled in the study. 77 patients accepted a single dose of dexamethasone and furosemide administration (EXP group, n = 77), and 70 patients did not (CON group, n = 70). Demographic and perioperative data, inflammatory markers including interleukin-6 (IL-6) and procalcitonin (PCT), and clinical outcomes were compared between the two groups. RESULTS: Compared with the CON group, the incidence rate of urosepsis of the EXP group were significantly lower (11.69% vs. 24.29%, p = 0.046). 3 patients developed severe urosepsis in the EXP group, while 5 patients developed severe urosepsis in the CON group. Compared with those in the CON group, the patients with postoperative urosepsis in the EXP group showed lower serum levels of IL-6 at postoperative hour two (p = 0.045) and at postoperative day one (p = 0.031) and lower serum levels of PCT at postoperative day one (p = 0.015). There was a better clinical outcome of a shorter postoperative hospital stay (p = 0.015) in patients with postoperative urosepsis in the EXP group than in those in the CON group. CONCLUSION: The perioperatively combined application of dexamethasone and furosemide was beneficial for alleviating postoperative inflammatory reaction and caused a better clinical outcome of a shorter postoperative hospital stay.