Costunolide Inhibits Chronic Kidney Disease Development by Attenuating IKKß/NF-κB Pathway.

Background: Chronic kidney disease (CKD) is a significant worldwide health concern that leads to high mortality rates. The bioactive substance costunolide (CTD) has demonstrated several pharmacological effects and holds promise as a CKD treatment. This study aims to investigate the impact of CTD on CKD and delve into its mechanisms of action. Methods: Unilateral ureteral obstruction (UUO) methods and renal fibrosis mice models were created. Various concentrations of CTD were injected into UUO mice models to investigate the therapeutic effects of CTD on renal fibrosis of mice. Then, renal morphology, pathological changes, and the expression of genes related to fibrosis, inflammation and ferroptosis were analysed. RNA sequencing was utilized to identify the main biological processes and pathways involved in renal injury. Finally, both overexpression and inhibition of IKKß were studied to examine their respective effects on fibrosis and inflammation in both in vitro and in vivo models. Results: CTD treatment was found to significantly alleviate fibrosis, inflammation and ferroptosis in UUO-induced renal fibrosis mice models. The results of RNA sequencing suggested that the IKKß acted as key regulatory factor in renal injury and the expression of IKKß was increased in vitro and in vivo renal fibrosis model. Functionally, down-regulated IKKß expression inhibits ferroptosis, inflammatory cytokine production and collagen deposition. Conversely, IKKß overexpression exacerbates progressive renal fibrosis. Mechanistically, CTD alleviated renal fibrosis and inflammation by inhibiting the expression of IKKß and attenuating IKKß/NF-κB pathway. Conclusion: This study demonstrates that CTD could mitigate renal fibrosis, ferroptosis and inflammation in CKD by modulating the IKKß/NF-κB pathway, which indicates targeting IKKß has an enormous potential for treating CKD.

The value of audiovisual sexual stimulation with virtual reality in diagnosing erectile dysfunction.

Background: The traditional audiovisual sexual stimulation (AVSS) test may experience limitations including low erectile response rate and lack of unified diagnostic criteria. Aim: We aimed to explore the clinical value of AVSS with virtual reality (VR-AVSS) test in assessing erectile function and diagnosing erectile dysfunction (ED). Methods: Participants 18 to 60 years of age were screened for analysis in 3 clinical centers from June 2020 to March 2022. Demographic data, 5-item International Index of Erectile Function (IIEF-5), erectile hardness score (EHS), and self-reported symptom questions were collected. The ED patients and control patients were confirmed according to the IIEF-5 and EHS. All subjects watched a 60-minute erotic video by VR device during RigiScan recording. The parameters including tip average rigidity, tip effective erectile duration (duration of rigidity ≥60%, tip effective erectile duration), base average rigidity, and base effective erectile duration were evaluated. Outcomes: The main outcome of interest was the application of VR immersion technology to improve the traditional AVSS test. Results: A total of 301 ED cases and 100 eligible control patients were included for final analysis. Compared with control patients, ED cases had significantly lower IIEF-5 scores, EHS, positive response rate, and erectile rigidity and duration. The positive response rate of ED and control patients were 75.5% and 90.9%, respectively. The cutoff points of tip average rigidity, tip effective erectile duration, base average rigidity, and base effective erectile duration were 40.5% (sensitivity: 77.6%, specificity: 70.2%; P < .001), 4.75 minutes (sensitivity: 75.9%, specificity: 75.4%; P < .001), 48.5% (sensitivity: 77.6%, specificity: 75.1%; P < .001), and 7.75 minutes (sensitivity: 79.3%, specificity: 75.7%; P < .001). Clinical Implications: The technological superiority of VR will enable the VR-AVSS immersion test to be a more accurate detection than traditional AVSS modes. Strengths and Limitations: Our study applied VR immersion technology to establish the standard operation procedure for the AVSS test, which could effectively reduce the interference of adverse factors and minimize the detecting errors. However, the test data only included positive response subjects, so the true erectile status of men with a negative response to the AVSS test cannot be obtained. Conclusions: The VR-AVSS test can effectively improve the diagnostic accuracy of ED. The average rigidity and effective erectile duration were the optimal diagnostic parameters for excluding ED.

A prospective randomized controlled study on scheduled PDE5i and vacuum erectile devices in the treatment of erectile dysfunction after nerve sparing prostatectomy.

Cavernous nerve injury is an important cause of erectile dysfunction (ED). Although protective nerve technology has been widely used in nerve-sparing radical prostatectomy (nsRP), the incidence of ED is still very high after surgery. The purpose of our study was to evaluate erectile function (EF) and penile length in the non-erectile state (PLNES) following scheduled phosphodiesterase 5 inhibitor (PDE5i), vacuum erectile device (VED) treatment, and combination therapy after nsRP. One hundred patients with localized prostate cancer and normal EF were randomized to scheduled PDE5i group, VED treatment group, a combined treatment group, and the control group without any intervention. The International Index of Erectile Function-5 (IIEF-5) scores and PLNES were evaluated after 6 months and 12 months of treatment. Sexual Encounter Profile (SEP-Question 2 and SEP-Question 3) were evaluated after 12 months of treatment. Ninety-one of the 100 randomized patients completed the study. We found that the 5 mg tadalafil once a day (OaD) combined with VED can help improve IIEF-5 scores in nsRP patients after both 6 months and 12 months. VED alone or combined with tadalafil OaD can help patients maintain PLNES. VED combined with tadalafil OaD can improve the rate of successful penetration (SEP-Question 2) after 12 months. There were no significant differences in the return to target EF after 12 months among the groups. No significant correlation was noted between the variables and return to target EF (IIEF ≥ 17), and between the variables and effective shortening of the patient's penis (shortening ≥ 1 cm) after 12 months of intervention.

[Effect of Shanhaidan Granules combined with tadalafil on erectile dysfunction: A multi-center clinical trial].

OBJECTIVE: To observe the clinical effect and safety of Shanhaidan Granules (SHDG) combined with tadalafil tablets (TT) in the treatment of ED. METHODS: In this open multi-center case-control clinical trial, we enrolled 247 ED patients according to the designed criteria, and treated them orally with SHDG at 10 g per time tid (n = 74), TT at 5 mg per time bid (n = 52), or SHDG + TT at the above doses (n = 121), all for 8 weeks. Before and after medication, we recorded the IIEF-6, erection hardness scores (EHS), traditional Chinese medicine syndromes (TCMS) scores, penile cavernous blood flow parameters and adverse reactions, and compared them between the 3 groups of patients. RESULTS: After 8 weeks of treatment, all the patients showed significantly increased IIEF-6, EHS and TCMS scores in comparison with the baseline (P < 0.05). The total effectiveness rates in the SHDG, TT and SHDG + TT groups were 60.8%, 67.3% and 69.4% respectively based on the IIEF-6 scores, remarkably higher in the TT and SHDG + TT groups than in the SHDG group (P < 0.05), and 40.5%, 32.7% and 63.6% respectively according to the TCMS scores, markedly higher in the SHDG and SHDG + TT groups than in the TT group (P < 0.05). Single-center data manifested significantly increased peak systolic velocity (PSV) of the penile artery in the SHDG + TT and TT groups (P < 0.05). The improvement values of relevant parameters were remarkably higher in the SHDG + TT group than in the TT and SHDG groups, so were IIEF-6 scores in the TT than in the SHDG group, and TCM syndromes in the SHDG than in the TT group. No medication-related adverse events were found in any of patients after treatment, except for some mild side effects including muscle soreness and gastrointestinal reactions in a few cases, all soon relieved, none with abnormalities in blood and urine routine tests or hepatic and renal function indicators. CONCLUSIONS: Shanhaidan Granules combined with tadalafil can significantly improve the erectile function and reduce TCM syndromes in ED patients, and therefore can be applied effectively and safely in clinical practice./.

Hypoxic Preconditioning Enhances Cellular Viability and Pro-angiogenic Paracrine Activity: The Roles of VEGF-A and SDF-1a in Rat Adipose Stem Cells.

To achieve the full therapeutic potential of implanted adipose stem cells (ASCs) in vivo, it is crucial to improve the viability and pro-angiogenic properties of the stem cells. Here, we first simulated the conditions of ischemia and hypoxia using the in vitro oxygen-glucose deprivation (OGD) model and confirmed that hypoxic preconditioning of ASCs could provide improved protection against OGD and enhance ASC viability. Second, we assessed the effect of hypoxic preconditioning on pro-angiogenic potential of ASCs, with a particular focus on the role of vascular endothelial growth factor-A (VEGF-A) and stromal derived factor-1a (SDF-1a) paracrine activity in mediating angiogenesis. We found that the conditioned medium of ASCs (ASCCM) with hypoxic preconditioning enhanced angiogenesis by a series of angiogenesis assay models in vivo and in vitro through the upregulation of and a synergistic effect between VEGF-A and SDF-1a. Finally, to investigate the possible downstream mechanisms of VEGF/VEGFR2 and SDF-1a/CXCR4 axes-driven angiogenesis, we evaluated relevant protein kinases involved the signal transduction pathway of angiogenesis and showed that VEGF/VEGFR2 and SDF-1a/CXCR4 axes may synergistically promote angiogenesis by activating Akt. Collectively, our findings demonstrate that hypoxic preconditioning may constitute a promising strategy to enhance cellular viability and angiogenesis of transplanted ASCs, therein improving the success rate of stem cell-based therapies in tissue engineering.

Effect of low-intensity extracorporeal shockwave therapy on nocturnal penile tumescence and rigidity and penile haemodynamics.

The study aims to evaluate the effect of low-intensity extracorporeal shockwave therapy (Li-ESWT) on nocturnal erection and penile haemodynamics. Patients with erectile dysfunction (ED) were enrolled from January 2018 to March 2019. Self-reported erectile symptoms, the International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Scores (EHS), nocturnal penile tumescence and rigidity (NPTR) and cavernous duplex Doppler ultrasound (CDDU) were evaluated. NPTR and CDDU were evaluated by Rigiscan and vascular ultrasound system respectively. Comparisons of NPTR and CDDU parameters were performed before and after Li-ESWT (Renova, once a week, 4 weeks in total). A total of 35 cases (mean age 36.51 ± 11.47 years) were enrolled for analysis. The IIEF-5 (10.60 ± 5.99 vs. 15.13 ± 6.22, p = .003), EHS (p = .016) and self-reported erectile hardness (p = .014) were significantly improved after 1-month treatment. Nocturnal erection frequency (p = .010), duration of total erection (p = .017), duration of erectile rigidity ≥60% at penile tip and base (p = .014 and p = .002) and the best erectile rigidity at penile tip and base (p = .012 and p = .005) improved significantly after treatment. However, no CDDU parameters improved after Li-ESWT (all p > .05). Li-ESWT can effectively improve subjective erectile function and nocturnal erection in ED patients. Large sample and well-designed studies need to be developed for supporting the current findings.

Free testosterone correlated with erectile dysfunction severity among young men with normal total testosterone.

Erectile dysfunction (ED) due to androgen deficiency is rare in the young population. We retrospectively evaluated in this study men aged 18-40 years presenting with ED from 2015 to 2017. The International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Grade Scores (EHGS) were used to assess erectile function. Total testosterone (TT), sex hormone-binding globulin (SHBG), lipid profile, and glycometabolic indicators were tested in fasting blood sample. TT and SHBG were detected by electrochemiluminescence immunoassay, and free (FT) and bio-available testosterone (BT) were calculated from a validated formula. Linear regression was used to analyze the data. In total, 140 cases (30.56 ± 4.81 years) with a mean TT levels of 6.15 ± 2.17 ng/ml were enrolled. Decreased levels of FT were associated with lower IIEF-5 scores(ß = 0.176, P = 0.048) and EHGS (ß = 0.198, P = 0.026) after adjustment for age, body mass index (BMI), smoking, comorbidities, high-sensitive C-reactive protein (hsCRP), uric acid, fructosamine, and quantitative insulin sensitivity check index (QUICKI). TT was only associated with EHGS in the crude model (ß = 0.177, P = 0.037) and some single factor adjustment models, whereas BT and SHBG were not related with erectile function in any model. Low FT level, even in the presence of normal TT, is associated with ED severity in young men. FT levels should be screened in ED patient even with normal total testosterone.

[Updated cytokine therapy of erectile dysfunction].

Four types of cytokines are found to be related to the pathogenesis and treatment of ED. The cytokines capable of promoting angiogenesis can improve vascular endothelial function, promote endothelial regeneration and thus improve erectile function, those capable of promoting nerve regeneration can improve erectile function by protecting cavernous nerves, those capable of protecting the smooth muscle function can improve erectile function by promoting the smooth muscle expression and inhibiting penile fibrosis, and those inflammation-related cytokines can induce penile erection by acting on the corresponding receptor relaxing smooth muscle. Compared with PDE-5 inhibitors, cytokines are more targeted for the treatment of ED. However, current studies are mostly dependent on rat models and lack of large sample sizes, which has restricted further clinical application of cytokines. Although VEGF, IGF-1, BDNF and NGF can significantly improve the erectile function of ED rats, experiments with larger samples and larger animals are needed to further confirm their efficacy and safety.

The morphological regeneration and functional restoration of bladder defects by a novel scaffold and adipose-derived stem cells in a rat augmentation model.

BACKGROUND: Due to the multilineage differentiation ability and paracrine role of adipose-derived stem cells (ASCs) for bladder defect repair, various scaffolds have been applied in combination with ASCs to promote bladder regeneration and restore bladder function. However, the low survival rate of ASCs and the difficulty of promoting bladder functional recovery are still unsolved. To explore these problems, we investigated the feasibility of a novel scaffold seeded with ASCs in a rat model of bladder augmentation. METHODS: A novel autologous myofibroblast (AM)-silk fibroin (SF) scaffold was harvested after subcutaneously prefabricating the bladder acellular matrix grafts (BAMG) and SF by removing the BAMG. The AM-SF scaffolds were then seeded with ASCs (AM-SF-ASCs). Fifty percent supratrigonal cystectomies were performed followed by augmenting the cystectomized defects with AM-SF scaffolds or AM-SF-ASCs. The histological and functional assessments of bladders were performed 2, 4, and 12 weeks after surgery while the ASCs were tracked in vivo. RESULTS: For bladder tissue regeneration, immunofluorescence analysis revealed that AM-SF-ASCs (the experimental group) promoted better morphological regeneration of the urothelium, vessels, bladder smooth muscle, and nerve than AM-SF scaffolds (the control group). Regarding functional restoration, the AM-SF-ASC group exhibited higher bladder compliance and relatively normal micturition pattern compared to the AM-SF group. In addition, a certain number of surviving ASCs could be found in vivo 12 weeks after implantation, and some of them had differentiated into smooth muscle cells. CONCLUSIONS: The AM-SF scaffolds with ASCs could rapidly promote bladder morphological regeneration and improved bladder urinary function. In addition, the bag-shaped structure of the AM-SF scaffold can improve the survival of ASCs for at least 12 weeks. This strategy of AM-SF-ASCs has a potential to repair large-scale bladder defects in the clinic in the future.

[Animal models of erectile dysfunction: Establishment and evaluation].

At present, the study of erectile dysfunction depends heavily on animal models, but the differences in anatomy and physiology of currently used animals make it difficult to exceed the limitations on the experiment. In order to make the results of experiments more applicable and beneficial to the public, it is essential to establish most suitable animal models for the study of the sexual function of humans. Moreover, a consensus has not yet been reached on the methods of detecting and evaluating the erectile function of animals, and therefore an informative and instructional summary of the existing methods seems even more necessary. This article discusses how to establish and evaluate the animal models of different types of erectile dysfunction.

The combination of herbal medicine Weng-li-tong with Tolterodine may be better than Tolterodine alone in the treatment of overactive bladder in women: a randomized placebo-controlled prospective trial.

BACKGROUND: To assess the efficacy and safety of the herbal medicine, Weng-li-tong (WLT) as monotherapy or combined with tolterodine in women with overactive bladder (OAB). METHODS: A prospective, randomized, single-blind multi-center trial was performed which included 182 OAB patients treated with either placebo (n = 26), WLT (n = 52), tolterodine (n = 52) or WLT plus tolterodine (n = 52). The overactive bladder symptom score (OABSS) and micturition behavior were measured to evaluate treatment efficacy. RESULTS: In total, 146 patients [placebo (n = 23), WLT (n = 39), tolterodine (n = 41) and WLT plus tolterodine (n = 43)] completed 8 weeks of treatment. Compared to those treated with placebo, patients in three intervention groups showed significant improvements in the OABSS, voiding frequency, average voided volume and urgency incontinence. WLT had a slower onset than tolterodine or combination therapy in reducing urgency incontinence. Compared with tolterodine, WLT had a weaker effect in improving OABSS (P = 0.022) and daily voiding frequency (P = 0.034). The combination therapy had better efficacy than WLT or tolterodine alone in improving the OABSS, voiding frequency and voided volume. No significant differences in the changes in quality of life scores were observed among the three intervention groups. Residual urine increased significantly in tolterodine group (P = 0.004), but not in combination group. WLT resulted in fewer adverse effects than tolterodine such as dry mouth (P = 0.002), weak stream (P = 0.002) and less residual urine (P < 0.001). CONCLUSIONS: WLT could improve OAB symptoms in women, while it had slower onset and weaker efficacy but fewer adverse effects than tolterodine. The combination of WLT and tolterodine was more efficacious than tolterodine alone in improving OAB symptoms. TRIAL REGISTRATION: Chinese Clinical Trial Registry [ ChiCTR-IPR-14005626 ]. Date of registration: 7 December 2014.

Time-dependent bladder tissue regeneration using bilayer bladder acellular matrix graft-silk fibroin scaffolds in a rat bladder augmentation model.

With advances in tissue engineering, various synthetic and natural biomaterials have been widely used in tissue regeneration of the urinary bladder in rat models. However, reconstructive procedures remain insufficient due to the lack of appropriate scaffolding, which should provide a waterproof barrier function and support the needs of various cell types. To address these problems, we have developed a bilayer scaffold comprising a porous network (silk fibroin [SF]) and an underlying natural acellular matrix (bladder acellular matrix graft [BAMG]) and evaluated its feasibility and potential for bladder regeneration in a rat bladder augmentation model. Histological (hematoxylin and eosin and Masson's trichrome staining) and immunohistochemical analyses demonstrated that the bilayer BAMG-SF scaffold promoted smooth muscle, blood vessel, and nerve regeneration in a time-dependent manner. At 12weeks after implantation, bladders reconstructed with the BAMG-SF matrix displayed superior structural and functional properties without significant local tissue responses or systemic toxicity. These results demonstrated that the bilayer BAMG-SF scaffold may be a promising scaffold with good biocompatibility for bladder regeneration in the rat bladder augmentation model.

Two-stage urethroplasty is a better choice for proximal hypospadias with severe chordee after urethral plate transection: a single-center experience.

It is still debatable whether single- or two-stage urethroplasty is a more suitable technique for treating hypospadias with severe chordee after urethral plate transection. This retrospective study evaluated these two techniques. A total of 66 patients of proximal hypospadias with severe chordee were divided into two groups according to the techniques they underwent: 32 and 34 patients underwent single-stage (Duckett) or two-stage urethroplasty, respectively. Median ages at presentation were 7.5 years and 11.0 years in single-stage and two-stage repair groups, respectively. Median follow-ups were 28.5 months (20-60 months) and 35 months (18-60 months) in the single-stage and two-stage groups, respectively. The meatus of the neourethra was located at the top of the glans in all patients. No recurrence of chordee was found during follow-up, and all patients or parents were satisfied with the penile length and appearance. Complications were encountered in eight patients in both groups, with no statistically significant differences between the two techniques. The late complication rate of stricture was higher after the single-stage procedure (18.75% vs 0%). The complication rate after single-stage repairs was significantly lower in the prepubescent subgroup (10.52%) than in the postpubescent cohort (46.15%). These results indicate that the urethral plate transection effectively corrects severe chordee associated with proximal hypospadias during the intermediate follow-up period. Considering the higher rate of stricture after single-stage urethroplasty, two-stage urethroplasty is recommended for proximal hypospadias with severe chordee after urethral plate transection.

The differentiation of human adipose-derived stem cells towards a urothelium-like phenotype in vitro and the dynamic temporal changes of related cytokines by both paracrine and autocrine signal regulation.

PURPOSE: To investigate the differentiation ability of human adipose-derived stem cells (ASCs) towards urothelium-like cells in vitro and the dynamic changes of related cytokines and cytokine receptors in the culture medium. MATERIALS AND METHODS: The ASCs were induced using both conditioned media (CM) and the transwell co-culture system with an immortalized urothelium cell line (SV-HUC-1,HUC) for 21 days. Protein and mRNA expression of the mature urothelium specific markers uroplakin-IA (UP-1A) and uroplakin-II (UP-II) were detected by immunofluorescence and quantitative real-time PCR, respectively. Array detection was used to screen 41 cytokines and receptors in the upper medium of urothelium, non-induced ASCs and urothelium-induced ASCs at three time points, early (12 hours), intermediate (7 days) and late (21 days). RESULTS: After induction for 7 days, the ASCs grown in both CM and transwell co-culture system expressed uroplakin-IA (13.54±2.00%; 17.28±1.84%) and uroplakin-II (19.49±1.73%; 13.98±1.47%). After induction for 21 days, ASCs grown in co-culture had significantly increased expression of uroplakin-IA (48.03±1.25%; 49.57±2.85%) and uroplakin-II (45.38±2.50%; 46.58±1.95%). In the upper medium of urothelium, 28 cytokines and 8 cytokine receptors had significantly higher expression than the counterpart of non-induced ASCs. After 7 days induction, the expression of 22 cytokines and 8 cytokine receptors was significantly elevated in the upper medium of induced ASCs compared to non-induced ASCs. At the early and intermediate time points, ASCs secreted high levels of relative cytokines and soluble receptors, but their expressions decreased significantly at the late time point. CONCLUSION: The adipose-derived stem cells have the potential to be differentiated into urothelium-like cells in vitro by both CM and transwell co-culture system with mature urothelium. Numerous cytokines and receptors were involved in the differentiation process with dynamic temporal changes by both paracrine and autocrine signal regulation. Further studies should be carried out to determine the detailed mechanism of cytokines and receptors and to enhance the urothelium differentiation efficiency of ASCs.

[Application of adipose-derived stem cells in lower urinary tract reconstruction].

Adipose-derived stem cells have self-renewal and multi-differentiation potentials, which can differentiate into smooth muscle cells, urinary epithelial-like cells, endothelial cells, neuron-like cells, etc. and secrete a variety of growth factors. As a result, the research on adipose-derived stem cells in lower urinary tract reconstruction using tissue engineering has been a highlight in recent years. This review focuses on the application of adipose-derived stem cells as seed cells to lower urinary tract reconstruction by tissue engineering in such diseases as bladder defect, stress urinary incontinence, and erectile dysfunction.

Unsatisfactory outcomes of prolonged ischemic priapism without early surgical shunts: our clinical experience and a review of the literature.

Ischemic priapism is a rare occurrence which can cause severe erectile dysfunction (ED) without timely treatment. This retrospective study reports our experience in treating prolonged ischemic priapism and proposes our further considerations. In this paper, a total of nine patients with prolonged ischemic priapism underwent one to three types of surgical shunts, including nine Winter shunts, two Al-Ghorab shunts and one Grayhack shunt. During the follow-up visit (after a mean of 21.11 months), all patients' postoperative characters were recorded, except one patient lost for death. Six postoperative patients accepted a 25-mg oral administration of sildenafil citrate. The erectile function of the patients was evaluated by their postoperative 5-item version of International Index of Erectile Function Questionnaire (IIEF-5), which were later compared with their premorbid scores. All patients had complete resolutions, and none relapsed. The resolution rate was 100%. Seven patients were resolved with Winter shunts, one with an Al-Ghorab shunt and one with a Grayhack shunt. The mean hospital stay was 8.22 days. There was only one urethral fistula, and the incidence of postoperative ED was 66.67%. Four patients with more than a 72-h duration of priapism had no response to the long-term phosphodiesterase type 5 (PDE-5) inhibitor treatment. These results suggest that surgical shunts are an efficient approach to make the penis flaccid after prolonged priapism. However, the severe ED caused by prolonged duration is irreversible, and long-term PDE-5 inhibitor treatments are ineffective. Thus, we recommend early penile prosthesis surgeries for these patients.

A comparative study of the use of a transverse preputial island flap (the Duckett technique) to treat primary and secondary hypospadias in older Chinese patients with severe chordee.

OBJECTIVE: To investigate the outcome between the primary and secondary hypospadias with severe chordee in older patients by the transverse preputial island flap (TPIF). MATERIALS AND METHODS: We retrospectively analyzed 53 hypospadias patients who were performed with TPIF for urethroplasty, including 25 primary hypospadias (Group 1) and 28 secondary hypospadias (Group 2). The mean age in Group 1 was 12.12 ± 10.709 and 18.64 ± 8.727 in Group 2 (P = 0.0181). The mean follow-up time was 38.7 months (22-60 months). RESULTS: All of the foreskin flaps survived after the operation without necrosis. The overall complication rate was 24 % in Group 1 and 53.57 % in Group 2 (P = 0.0280). All the patients were also divided into two cohorts according to their ages in surgery. In the 0-10-yr cohort, there was a significant difference in the overall complication rate between the primary and secondary groups (P = 0.0173). But in the cases who were over 11 year old, there was no significant difference in the overall complications between two groups (P = 0.1603). Also no significant difference was found in the mean length of the urethral defect between two groups (P = 0.8312). CONCLUSION: The Duckett technique is an optional choice for some older Chinese patients undergoing primary operations, but it has a higher complication rate in those who have undergone previous failed urethroplasties. The unsatisfactory results found in the reoperative group were supposed to be linked to the older age, the lack of subcutaneous flap coverage and local scar tissue, but not to the length of the urethral defect.

[Repair and functional reconstruction of the penis (a report of 62 cases)].

OBJECTIVE: To investigate the effects of surgery treatment on serious penile lesions and malformation. METHODS: Sixty-two patients, aged from 19 to 63 years old (mean 35 ys), were included in the study. Among them, 4 patients suffered from penis partial defection were respectively treated with restoring defective penis, penis lengthening and urethroplasty; three patients with penis completely missing were treated with penis reconstruction surgery; 22 cases with serious penile curvature were treated with the 16-dot plication technique (Lue's procedure); 15 cases with penile fracture were treated with conservative treatment for 1 case and with patch penis, corpus spongiosum, and deep penile dorsal vein ligation for 14 cases; 5 cases with post-operative complications of 3-pieces of penile prosthesis, including the prosthesis perforating to the urethra, water pump failure, broken connection tube, erection angle < 60 degrees and failure to expansion the corpus cavernosum, were treated by taking out prostheses, urethral repair cracks, replacement of the prostheses, excision of fibrosis scar and re-implantation prostheses respectively. Four cases with penis complete amputation were treated with the penis replantation; three cases of avulsion injury were treated with the replantation and free flap skin; 6 with Paget's disease of penises were treated with the lesion free skin buried in the scrotum and penis. RESULTS: All these patients were followed up for 3 months to 4 years, with the average of 9 months. Among the 4 cases of penis partial defection, 2 patients were satisfied with the penile appearance and sexual function; 1 got some satisfactory and 1 was unsatisfied. Three cases with the loss of the penis completely were satisfied with both the postoperative appearance and urination, and 1 was not satisfied. Twenty-two cases of penile curvature deformities were corrected, and one case was recurrence. Fourteen of the 15 patients with penile fracture were followed, and all got the restoration of sexual function. Among them, 5 cases with post-operative complications, including mild bending, algopareunia, subcutaneous induration, poor hardness and poor sexual pleasure, were not further treated, and another case lost; Five cases with post-operative complications of three-pieces penile prosthesis were treated successfully, and 4 of their spouses were satisfied with their sexual function after operation, only 1 of their spouse not satisfied. Among four cases with complete amputation of penis, two cases of penis were replanted successfully while two necrosis. Three cases with avulsion were treated with skin grafting successfully. All 6 cases with penile Paget's disease were followed for 2 -4 years, and free skin grafts were all survival. One patient died of brain metastases 18 months after operation and five cases were disease-free survival. CONCLUSION: The patients should be treated based on the procedure of andrological and urological surgery, together with microsurgical, flap or skin graft technique. The urologist should design personalized surgical procedure. Most of the patient's penis shape and erectile dysfunction can be reconstructed by our procedures, but some patients can not achieve the desired appearance or function of penis. New approaches of the treatment ought to be developed to restore both of the shape and function for those severe injury of the penis.

[Human foreskin acellular matrix graft: a good scaffold for urethral tissue engineering].

OBJECTIVE: To provide evidence of using the human foreskin acellular matrix graft for urethral tissue engineering. METH-ODS: The human foreskin acellular matrix graft was prepared, its safety and biocompatibility as urethral material were determined by histological observation, cytotoxicity test using primary epithelial cells and experiment in vivo. RESULTS: Intact cells were absent from the foreskin acellular matrix graft. The cytotoxicity test showed that the relative growth rate of the cells was between 75% and 99%, and the cytotoxicity of the foreskin acellular matrix graft was grade 1, consistent with the national standard. With the lengthening of time, the foreskin acellular matrix graft became perfectly compatible with the urothelial cells and the urethral multi-layer structure was restored to normal gradually. CONCLUSION: The human foreskin acellular matrix graft, with its low antigenicity and good biocompatibility, could be a good scaffold for urethral tissue engineering.

[Construction of urethra mucosa structure in vitro by tissue engineering].

OBJECTIVE: To construct a structure of urethra mucosa in vitro by tissue engineering. METHODS: Primary porcine urothelial cells (UC) were obtained from the porcine bladder by enzymatic digestion and detected by immunofluorescence and RT-PCR. Bladder acellular matrix grafts (BAMG) were prepared, used as the scaffold and then evaluated by HE staining, Masson's trichrome staining, immunohistology and scanning electron microscopy. After in vitro culture and amplification, the UCs were seeded on the luminal surface the BAMGs. RESULTS: After 1 week of in vitro culture, the UCs formed a multilayer structure on the luminal surface of the BAMGs along the basement membrane. The tissue-engineered urothelium and BAMG complex was well formed and pan cytokeratins were positively expressed in the UCs on the scaffold. CONCLUSION: By tissue engineering, the urethra mucosa structure can be rapidly constructed in vitro, which can be applied to the repair of such urethral defect as hypospadias and urethral stricture.