Combination of mesenchymal stem cell injection with icariin for the treatment of diabetes-associated erectile dysfunction.

The present study was aimed to examine whether icariin, a traditional Chinese medicine, could improve therapeutic effects of adipose derived mesenchymal stem cells (ADSCs) for diabetes-associated erectile dysfunction (DMED). DMED were induced in rats by intraperitoneal injection of streptozotocin and confirmed by erectile function measurement. Then, rats of diabetic ED were randomly divided to receive the treatment of saline, ADSCs, icariin or ADSCs combined with icariin respectively. Compared with the treatment by ADSCs or icariin alone, intracavernosum injection of ADSCs combined with the following daily gastric gavage of icariin significantly augmented the value of ICP and ICP/MAP (p<0.01). Meanwhile, the survival of transplanted ADSCs was much improved due to the application of icariin. Similarly, immunofluorescent staining analysis demonstrated that the improved erectile tissue structure by combination of ADSCs and icariin was significantly associated with the increased expression of endothelial markers (vWF) (p<0.01) and smooth muscle markers (α-SMA) (p<0.01). Furthermore, the structure changes in corpus cavernosum were further confirmed by the Masson's trichrome staining. To explore the possible mechanism underlying icariin-enhanced therapeutic efficacy of MSCs, we employed an in vitro testing system by introducing H2O2 to imitate oxidative stress condition considering the oxidative environment faced by engrafted ADSCs and anti-oxidative capacity of icariin. In vitro, we found that the addition of icariin considerably reduced the apoptosis of ADSCs, and attenuated the intracellular reactive oxygen species (ROS), the superoxidase dismutase (SOD) activity and the lactate dehydrogenase (LDH). Subsequently, we examined the expression of apoptosis-related proteins and explored the potential signaling pathway through which icariin promoted the survival of ADSCs against oxidative stress. It was demonstrated that icariin significantly inhibited the upregulation of apoptosis-related proteins under oxidative condition, including Bax and cleaved caspase-3, while promoted the expression of anti-apoptotic factor BCL2. These effects were accompanied with the activation of signal molecules, PI3K/Akt and STAT3. The further signal protein inhibition assays exhibited that the suppression of STAT3 abrogated the icariin-mediated anti-apoptotic effects observed above, while did not influence the expression of PI3K/Akt. However, PI3K inhibition could abrogate icariin-mediated STAT3 activation and achieved a similar effect as STAT3 inhibition. Our results suggested that icariin was an effective adjuvant for enhancing ADSC-based therapy of DMEM, which may be ascribed to their protection of ADSCs against oxidative stress via the regulation of PI3K/Akt-STAT3 signal pathway.

Efficacy and Safety of Transurethral Photoselective Greenlight(™) Laser Vaporization for the Treatment of Orthotopic Ureteroceles in Adults.

OBJECTIVE: This study aimed to retrospectively evaluate the safety and efficacy of transurethral photoselective Greenlight(™) laser vaporization in adult patients with orthotopic ureterocele. MATERIALS AND METHODS: Thirty adult patients diagnosed with orthotopic urecterocele were recruited at our center. Transurethral photoselective Greenlight laser vaporization was used as the exclusive technique for endoscopic management during the study period. Information, including age, gender, mode of presentation, ureterocele size, vesicoureteral reflux, hydronephrosis status, and incidence of reoperation, were collected for evaluation. RESULTS: Our series included 12 men and 18 women. The mean patient age at presentation was 30.5 years (range, 18-62 years). The mean size of ureterocele was 18 mm (range, 10-41 mm). All patients successfully underwent transurethral photoselective Greenlight laser to vaporize the ureterocele. The operation ranged from 13 min to 38 min (mean 19.6 min). The average blood loss was <10 mL. No patient had intraoperative complications. The average postoperative hospital stay was 18.3 h. All patients were voided after postoperative catheter removal. None of the patients demonstrated any residual ureterocele and/or hydronephrosis when evaluated with ultrasonography after 3 months. Only one patient with a duplex collecting system presented asymptomatic low-grade reflux at 3 months, which was spontaneously resolved after 6 months of follow-up. All patients were free of any symptoms. No reoperative procedures were required at a mean follow-up of 14.2 months (range, 8-16). CONCLUSIONS: Transurethral photoselective Greenlight laser vaporization is safe, effective, and efficient for the management of orthotopic urecteroceles in adults. Therefore, this technique should be considered as the initial treatment in most patients.

Comparing the treatment outcomes of potassium-titanyl-phosphate laser vaporization and transurethral electroresection for primary nonmuscle-invasive bladder cancer: A prospective, randomized study.

BACKGROUND AND OBJECTIVES: In urology, potassium-titanyl-phosphate (KTP) laser is mainly used in the treatment of benign prostatic hyperplasia with a low rate of intraoperative and postoperative complications. A prospective, randomized study was undertaken to investigate the treatment outcomes of KTP laser vaporization for primary non-muscle-invasive bladder tumors (NMIBTs) as compared with conventional monopolar transurethral resection of bladder tumors (TURBT). MATERIALS AND METHODS: This study was designed as a prospective, randomized trial. After institutional review board approval, 229 consecutive patients with NMIBTs were randomized to 2 groups. Among them, 116 patients underwent KTP laser vaporization of a bladder tumor (laser group) and 113 patients underwent standard transurethral electroresection of the bladder tumors using monopolar loop electrode (TURBT group). According to the prognostic factors for recurrence, all patients were divided into low, intermediate or high risk subgroups. The clinical data were recorded and compared between the two groups. RESULTS: Eighty-nine patients in laser group and 94 in TURBT group were evaluable for the study end points. The preoperative characteristics of the patients were comparable in the two groups. There was no statistical difference in operation time between the two groups. Patients in the laser group had fewer perioperative complications and more patients needed bladder irrigation in the TURBT group. Compared with laser group, patients in the TURBT group had longer catheterization time and hospitalization duration. There were no statistical differences in the oncologic results in term of 2-year recurrence rates as compared between the two groups. CONCLUSIONS: Our study demonstrated that using KTP laser, transurethral vaporization is an effective and safe treatment for the patients with primary NMIBT. Compared with traditional TURBT, the KTP laser surgery had fewer perioperative complications and similar oncological results.

Hypoxia precondition promotes adipose-derived mesenchymal stem cells based repair of diabetic erectile dysfunction via augmenting angiogenesis and neuroprotection.

The aim of the present study was to examine whether hypoxia preconditioning could improve therapeutic effects of adipose derived mesenchymal stem cells (AMSCs) for diabetes induced erectile dysfunction (DED). AMSCs were pretreated with normoxia (20% O2, N-AMSCs) or sub-lethal hypoxia (1% O2, H-AMSCs). The hypoxia exposure up-regulated the expression of several angiogenesis and neuroprotection related cytokines in AMSCs, including vascular endothelial growth factor (VEGF) and its receptor FIK-1, angiotensin (Ang-1), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), stromal derived factor-1 (SDF-1) and its CXC chemokine receptor 4 (CXCR4). DED rats were induced via intraperitoneal injection of streptozotocin (60 mg/kg) and were randomly divided into three groups-Saline group: intracavernous injection with phosphate buffer saline; N-AMSCs group: N-AMSCs injection; H-AMSCs group: H-AMSCs injection. Ten rats without any treatment were used as normal control. Four weeks after injection, the mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured. The contents of endothelial, smooth muscle, dorsal nerve in cavernoursal tissue were assessed. Compared with N-AMSCs and saline, intracavernosum injection of H-AMSCs significantly raised ICP and ICP/MAP (p<0.05). Immunofluorescent staining analysis demonstrated that improved erectile function by MSCs was significantly associated with increased expression of endothelial markers (CD31 and vWF) (p<0.01) and smooth muscle markers (α-SMA) (p<0.01). Meanwhile, the expression of nNOS was also significantly higher in rats receiving H-AMSCs injection than those receiving N-AMSCs or saline injection. The results suggested that hypoxic preconditioning of MSCs was an effective approach to enhance their therapeutic effect for DED, which may be due to their augmented angiogenesis and neuroprotection.

Effects of continuous passage on immunomodulatory properties of human adipose-derived stem cells.

Human adipose-derived stem cells (hADSCs) have the ability to influence immune response, and hence are key cell sources for tissue repair and regeneration. In this study we explored the effect of continuous passage on the immunomodulatory properties of hADSCs to provide some advises for large-scale production of hADSCs for clinical applications. We found that after continuous passage, the specific surface markers expression levels as well as the adipogenic and osteogenic differentiation capacities of hADSCs had no obvious changes. However, the secretion levels of IL-10 and HGF reduced dramatically along with passage numbers. Furthermore, the INF-γ level was found higher in which medium peripheral blood mononuclear cells were co-cultured with hADSCs with higher passage numbers. Also, the in vivo experiments showed that the peritonitis model mice, which were injected with higher passage numbers of hADSCs, tended to have higher levels of inflammation. All these together indicated that continuous passage has only minor effect on the cell phenotypes but will impair the immunomodulatory properties of hADSCs. This suggests that hADSCs could be prepared by continuous passage, but only those cells of lower passage numbers would be ideal therapeutic tools.

Impact of 160 W Greenlight laser vaporization of the prostate on erectile function: a prospective randomized controlled trial with 1-year follow-up.

OBJECTIVE: Our aim was to evaluate the impact of 160 W Greenlight laser vaporization of the prostate on erectile function by the International Index of Erectile Function (IIEF-5) in 1-year follow-up in patients with lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). BACKGROUND DATA: Although high-power Greenlight laser has greatly improved the efficiency of vaporization of the prostate, the impact of it on erectile function remains uncertain. MATERIALS AND METHODS: A total of 80 BPH patients with normal erectile function or mild erectile dysfunction (IIEF-5 ≥12) were included in this study. They were randomly assigned to two equal groups: 80 or 160 W. Both groups were compared regarding all relevant preoperative, operative, and postoperative parameters. Urinary function in terms of International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum flow rate (Qmax), and residual urinary volume (RUV) were evaluated at 1, 3, 6, and 12 months postoperatively. Erectile function was evaluated by IIEF-5 at 3, 6, and 12 months postoperatively. RESULTS: Baseline characteristics of the two groups were comparable. Mean operative time was significantly shorter for the 160 W group. Urinary function in terms of IPSS, QOL, Qmax, and RUV were all significantly improved over baseline in both groups. There were no significant differences in these urinary functional parameters between the two groups at any point of follow-up. IIEF-5 scores of both groups significantly decreased at 3 months postoperatively compared with baseline, but at 6 and 12 months postoperatively, IIEF-5 score of either group increased to baseline, and was not different from baseline. At any point of follow-up, IIEF-5 scores of the two groups were comparable. CONCLUSIONS: Greenlight laser (160 W) vaporization of the prostate will not increase the risk of impairing erectile function.

A retrospective evaluation of benign prostatic hyperplasia treatment by transurethral vaporization using a 1470 nm laser.

OBJECTIVE: This article aims to evaluate the safety and efficacy of a new diode laser at a wavelength of 1470 nm, in the surgical treatment of benign prostatic hyperplasia (BPH). BACKGROUND DATA: BPH is very common. Laser surgeries, such as photoselective vaporization of the prostate (PVP), have gained interest over the past decade because of their satisfying clinical results and reduced morbidity. METHODS: A total of 24 patients who underwent transurethral vaporization of the prostate with a new diode laser prototype at a wavelength of 1470 nm were included in this retrospective study. The baseline characteristics of patients and treatment outcomes were evaluated at 4 weeks after the operation with the International Prostate Symptoms Score (IPSS), duration of catheterization, and maximum urinary flow rate (Qmax). RESULTS: The mean age of patients was 69 ± 8.6 years. The mean time of operation and hospitalization were 97 ± 39 min and 5.3 ± 5.2 days, respectively. The mean duration of catheterization after surgery was 3.1 ± 2.7 days. No recatheterizations or secondary surgeries were required. IPSS and Qmax at 4 weeks postoperatively were significantly changed compared with the baseline (p<0.001). CONCLUSIONS: Transurethral vaporization of the prostate using a 1470 nm laser is effective to treat benign prostatic hyperplasia.

A prospective, randomized controlled trial of circumcision in adult males using the CO2 laser: modified technique compared with the conventional dorsal-slit technique.

OBJECTIVE: The purpose of this study was to investigate the safety and efficacy of a modified CO2 laser technique for circumcision in adult males as compared with the conventional dorsal-slit method. BACKGROUND DATA: Circumcision is one of the most commonly performed surgeries in the world. Although present techniques produce a good long-term result, there is a continuing need to improve the safety and efficacy of the circumcision procedure. MATERIALS AND METHODS: Data were analyzed from a prospective randomized controlled clinical study comparing two different operative techniques for adult circumcision: the modified CO2 laser circumcision technique, and the conventional dorsal-slit technique. A total of 300 patients >18 years of age were recruited in this study. Several perioperative data, including age, indications, operation time, intraoperative blood loss, complications, and postoperative pain were analyzed. Differences between the CO2 laser technique and the conventional technique were compared. RESULTS: There was no statistically significant difference in age distribution and indications between the two groups. Compared with the conventional group, there were shorter operative time, less blood loss and lower postoperative complication rate in the laser group. The CO2 laser technique was associated with much less pain, as quantitated by a 10 point visual analogue scale (VAS) pain score at both 1 day and 7 days postoperatively. CONCLUSIONS: The modified CO2 laser technique that we introduced offers a simple, safe, faster, and effective alternative method to the conventional technique in adult male circumcision, with decreased blood loss, pain, and complications.

[Follow-up observation of photoselective vaporization of prostate for treatment of benign prostatic hyperplasia within five years].

OBJECTIVE: To evaluate the efficacy and safty of photoselective vaporization of prostate (PVP) in the treatment of benign prostatic hyperplasia with obstruction within 5 years. METHODS: From December 2004 to December 2009, there were 782 cases have been except for neurogenic bladder dysfunction and prostate cancer, who received PVP surgical treatment of BPH. The surgical conditions and postoperative follow-up data were recorded and the follow-up cut-off time for surgery after 5 years. RESULTS: A total of 782 patients with BPH who underwent PVP were included in this retrospective study. The operation in 740 cases was successfully completed at one time. But in other 42 cases, the twice operation was performed. The mean operation time was (85 ± 38) minutes, and the mean energy delivery was (355 ± 124) kJ. The mean catheterization and postoperative hospitalization time was (2.3 ± 1.7) days and (5.2 ± 2.6) days, respectively. No severe intraoperative complications were observed. The mean follow-up was (44.1 ± 19.3) months. The shortest follow-up was 6 months. The longest follow-up was 5 years. Complete follow-up data were available for 398 of the 782 patients. Of the 398 patients followed up for 5 years, the mean international prostate symptom score after 5 years was 12.8 ± 6.9, quality of life score was 2.2 ± 1.6, maximal flow rate was (14.5 ± 2.4) ml/s, and residual urine volume was 58 ml (M50). The retreatment rate because of BPH was 2.3% (9/398). Urethral stricture and bladder neck contracture were observed in 1.5% and 0.5% of the patients, respectively. CONCLUSIONS: PVP has demonstrated remarkably consistent results for objective and subjective voiding parameters. Its late complication is rare and retreatment rate is low.

[The feasibility study of estimating energy consumption in photoselective vaporization of prostate based on the volume of prostate].

OBJECTIVE: To discuss the feasibility of estimating energy consumption of green laser in photoselective vaporization of prostate (PVP) based on the preoperative volume of prostate. METHODS: From January 2005 to January 2007, 260 patients with benign prostatic hyperplasia (BPH) had been treated with PVP. Preoperative prostatic volume and post-two-weeks-operative prostatic volume of each patient were measured by transrectal ultrasound (TRUS). Energy consumption and emission time of green laser were recorded during the operation. Then we calculated the amount of energy consumption needed in vaporizing one gramme prostatic tissue, evaluated the correlation of energy consumption and preoperative volume of prostate by means of correlation-regression analysis, and established its regression equation. RESULTS: The amount of energy consumption needed in vaporizing one gramme prostatic tissue was (6.9 ± 0.6)kJ. The correlation of energy consumption and preoperative volume of prostate was significantly positive linear correlated. Its regression equation was: Energy Consumption (kJ) = 4.7 x Preoperative Volume of Prostate (cm³) - 14.1. CONCLUSION: It is feasible to estimate energy consumption of green laser in PVP based on preoperative volume of prostate.