The efficacy and feasibility of free inner prepuce graft combined with Oradi flap urethroplasty for the treatment of the obliterated penile urethral atresic stricture / 中华泌尿外科杂志

Objective:To investigate the efficacy and feasibility of urethroplasty using inner prepuce graft combined with Orandi flap for the treatment of the obliterated penile urethral atresic stricture.Methods:From January 2016 to September 2019, the clinical data of 18 obliterated penile urethral stricture cases were analyzed retrospectively. All the patients were treated using inner prepuce flap combined with Orandi Flap. The average age of the patients was 62.1 years old (range 20-81 years old). Ten cases had suprapubic cystostomy before operation. The maximum flow rate was 1.6-6.2 ml/s, with an average of 4.2ml/s. The intubation general anesthesia and lithotomy position was used. The foreskin of penis was incised longitudinally. The urethra was exposed and the segment of stricture was opened longitudinally. The range of stricture length was measured with soft ruler, ranging from 2.0 to 7.5 cm, with an average of 5.0cm. After the fibrotic tissue was completely removed, the dorsal inner prepuce was incised with needed length and width for harvesting a free skin flap in order to transplant and reconstruct the dorsal urethral. The Orandi flap was used to cover the ventral urethra, and a F14-16 silicone catheter was retained. The length range of the inner prepuce graft was 2.0-7.5 cm, with an average of 5.1cm; the width was 1.2-1.8 cm, with an average of 1.4cm. The length of Orandi flap was 2.2-7.7 cm, with an average of 6.0cm; the width was 1.0-1.5 cm, with an average of 1.3 cm. The catheter was removed 3-4 weeks after operation. The patients were then followed up after 3, 6 and 12 months postoperatively and then with annual assessments for the symptoms, urinary flow rate, and urethrography or soft urethroscopy when necessary.Results:All of the 18 operations were completed successfully. The patients were followed up for 6-36 months, with an average of 22 months. There were 5 patients with terminal dripping, 4 patients with recurrent urinary tract infection within half a year after operation, and antibiotic treatment being effective. The quality of life scores at 3 months and 6 months after operation were 0.8 (0-2) and 0.6 (0-1), respectively, which were statistically significant compared with before operation ( P<0.001). Conclusions:The use of free inner prepuce flap combined with Orandi flap is an effective treatment for the obliterated penile urethral atresic stricture, especially for the patients who are unwilling or unsuitable to harvest the oral mucosa. It has the advantages of convenient harvesting and less complications.

Lineage reprogramming of fibroblasts into induced cardiac progenitor cells by CRISPR/Cas9-based transcriptional activators

Overexpression of exogenous lineage-determining factors succeeds in directly reprogramming fibroblasts to various cell types. Several studies have reported reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs). CRISPR/Cas9-mediated gene activation is a potential approach for cellular reprogramming due to its high precision and multiplexing capacity. Here we show lineage reprogramming to iCPCs through a dead Cas9 (dCas9)-based transcription activation system. Targeted and robust activation of endogenous cardiac factors, including GATA4, HAND2, MEF2C and TBX5 (G, H, M and T; GHMT), can reprogram human fibroblasts toward iCPCs. The iCPCs show potentials to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells . Addition of MEIS1 to GHMT induces cell cycle arrest in G2/M and facilitates cardiac reprogramming. Lineage reprogramming of human fibroblasts into iCPCs provides a promising cellular resource for disease modeling, drug discovery and individualized cardiac cell therapy.

Comparison of pedicled skin flap of foreskin for phalloplasty and Sugita surgical method in treatment of complete concealed penis / 中国修复重建外科杂志

Objective: To evaluate the effectiveness of pedicled skin flap of foreskin for phalloplasty and Sugita surgical method in the treatment of complete concealed penis. Methods: The clinical data of 46 children with complete concealed penis between January 2016 and January 2018 were analyzed retrospectively. Among which, 25 cases were treated with pedicled skin flap of foreskin for phalloplasty (group A) and 21 cases were treated with Sugita surgical method (group B) with an average age of 4.7 years (range, 2 years and 8 months to 11 years). At 3 months after operation, the concealed penis recovery was scored from three aspects of postoperative penis length (the difference of the penis length between at 3 months after operation and before operation), penis appearance, and skin appearance (the total score was 10). And the parents evaluation of satisfaction degree of penis exposure, penis appearance, and foreskin appearance after surgical correction was collected. Results: Eighteen cases (72.0%) in group A and 15 cases (71.4%) in group B were followed up with an average of 13 months (range, 3-36 months). The incisions healed well in both groups, and there was no flap dehiscence, infection, necrosis, and penile erectile dysfunction. The penile length of the two groups increased significantly at 3 months after operation ( P0.05). No penile retraction occurred in the two groups. And there was no significant difference between the two groups in penis appearance score, but the penis appearance score, skin appearance score, and total score of group A were significantly better than those of group B ( P<0.05). At 3 months after operation, the satisfaction rate of penis exposure in group A and group B was 88.9% and 80.0%, respectively, with no significant difference ( χ2=0.50, P=0.48); the satisfaction rate of penis appearance was 72.2% and 53.3%, and the satisfaction rate of foreskin appearance was 94.4% and 53.3%, respectively, and the differences were significant ( χ2=5.13, P=0.03; χ2=7.53, P=0.01). Conclusion: Both surgical methods are suitable for correction of complete concealed penis, and the penile length gets a satisfactory recovery. However, the lymphedema of the prepuce after Sugita surgical method is serious, which can easily lead to poor appearance of the penis after operation. In general, the effectiveness of pedicled skin flap of foreskin for phalloplasty is better than that of the Sugita surgical method.

The Relationship between Neonatal Circumcision, Urinary Tract Infection, and Health

The risk-benefit profile of neonatal circumcision is not clear. Most studies have focused on urinary tract infections but other health sequelae have not been evaluated. While evidence supports benefits of circumcision, a lack of randomized trials has been cited as a weakness. National guidelines provide mixed recommendations regarding neonatal circumcision. We review the weight of evidence and utilize current statistical methodology on observational data to examine the risks and benefits of neonatal circumcision.

Establishment of Immortalized Primary Human Foreskin Keratinocytes and Their Application to Toxicity Assessment and Three Dimensional Skin Culture Construction

In spite of frequent usage of primary human foreskin keratinocytes (HFKs) in the study of skin biology, senescence-induced blockage of in vitro proliferation has been a big hurdle for their effective utilization. In order to overcome this passage limitation, we first isolated ten HFK lines from circumcision patients and successfully immortalized four of them via a retroviral transduction of high-risk human papillomavirus (HPV) E6 and E7 oncogenes. We confirmed expression of a keratinocyte marker protein, keratin 14 and two viral oncoproteins in these immortalized HFKs. We also observed their robust responsiveness to various exogenous stimuli, which was evidenced by increased mRNA expression of epithelial differentiation markers and pro-inflammatory genes in response to three reactive chemicals. In addition, their applicability to cytotoxicity assessment turned out to be comparable to that of HaCaT cells. Finally, we confirmed their differentiation capacity by construction of well-stratified three dimensional skin cultures. These newly established immortalized HFKs will be valuable tools not only for generation of in vitro skin disease models but also for prediction of potential toxicities of various cosmetic chemicals.

Prepuce development in Mongolian boys / Монголын Анагаах Ухаан

BackgroundThe prepuce (foreskin) is a simple fold of skin formed from an outer keratinized layer and inner mucosallayer, lining a preputial sac and provides functions such as protective, erogenous, and immunologic. Theprepuce is normally non-retractile during neonatal development, as the inner epithelial lining of prepuceand glans adhere each other. Non retractile prepuces are common among young boys and normalpart of preputial development. However, unnecessary circumcision is widely practiced among youngadolescents due to poor understanding of foreskin and lack of medical indication.GoalTo assess preputial retractibility in Mongolian boys at various ages to determine natural process ofpreputial separation.Material and MethodsWe evaluated 1697 Mongolian boys aged 2 to 12. Preputial condition was classifi ed into 5 types basedon preputial retractability: type I-phimosis, type II–partial phimosis, type III–adhesion of prepuce, IV–normal, V–circumcised. We also prospectively evaluated 30 histological materials of patients (2-12 yearsold), who were treated by complete circumcision. The materials were fi xed 10% solution of formalin,embedded in paraffi n, stained with hematoxylin-eosin and examined by 3 pathologists.ResultsThe incidences of type I was 67.9% in 2 years old, 12% in 6years, and 4.1% in 10 years and1.1% in12 years old, respectively. On the contrary, the incidences of type IV were 15.4% in 2 years old, 29.8%in 6 years, 74.7% in 10 years and 91.6% in 12 years. Thecircumcisionswere0% in 2 years old, 5.7%in 6 years old, 2.9% in 10 years old and 5% in 12 years old. Most patients (76.7%) did not have anyhistological alterations of the skin and infl ammatory alteration, not lichen sclerosis, were observed in23.3% in histological examination followed by circumcision.Conclusion: Preputual separation increases with ages in boys and surgical treatment of the phimosisshould be performed with cautions.

Flexible dilatation combined with topical betamethasone cream in treatment of child phimosis / 中华全科医师杂志

Two hundred and twenty five children aged 4-12 years with phimosis were treated by flexible dilatation combined with topical betamethasone cream from January 2003 to January 2015.Two hundred and eight cases (92.44％) were completely cured and penile edema and urination were returned to normal 7 d after a single operation;while,17 children received 2-3 additional flexible expansion.During follow-up of 2-24 months,221 children achieved the cure standards with an overall cure rate of 98.22％.Flexible dilatation combined with topical betamethasone cream is effective modality for phimosis in children,with less surgical trauma and low complication rate.

Diagnosis and treatment of primary malignant melanoma of the foreskin / 局解手术学杂志

Objective To discuss the biological and pathological features, diagnosis, treatment and prognosis of primary malignant mel-anoma of the foreskin. Methods The diagnosis, treatment, and follow-up of one case of primary malignant melanoma of foreskin treated in our hospital was reported, and the related literatures were reviewed. Results The tumour stage of the patient was stage I, and the patient was given partial amputation of the penis and bilateral inguinal lymph node dissection. Chemotherapy and immunotherapy were conducted at the same time. And there was no recurrence metastasis of during the postoperative follow-up of 54 months. Conclusion Primary malignant melanoma of the foreskin is rare in clinical and it is of high malignant degree. Its diagnosis depends on pathology and surgery is the main treatment. Postoperative chemotherapy and immunotherapy can prolong the survival time of patients, but the overall prognosis is poor.

Compared the Efficacy of Circumcision Suture Surgery and Surgery Foreskin Cerclage Ring / 现代医院

Objective The curative effect comparison of circumcision suture surgery and surgery foreskin cerclage ring.Methods Selection in our department from July 2013 to October 2016 were selected from children with phimosis or re-dundant prepuce in children with a total of 562 cases as the research object , randomly divided into control group (182 cases) and observation group (380 cases).The observation group using disposable circumcision suture treatment , the control group using prepuce ring resection in the treatment of patients , observe the operation effect , two postoperative pain and complica-tions.Results The observation group operation success rate ( 100%) was significantly higher than the control group (94.09%), observation group operation time , intraoperative bleeding volume , postoperative 24h pain scores were signifi-cantly less than the control group , the adverse reaction rate of observation group ( 6.32%) was significantly lower than the control group (11.54%),the differences between groups were significantly P<0.05.Conclusion Ircumcision surgery su-ture is better than that of ring foreskin cerclage surgery , more safe and reliable .

Zip injuries: A simple solution.

Entrapment of penile foreskin between zipper teeth and zip slider is a common injury in children. It is seen in boys of age group 5-12 years who usually do not wear underpants. About 80% of these injuries occur accidentally while zipping up. Here, We have described a technique which is simple, quick, pain less and require no special instruments.

Antioxidant and anti-lipid peroxidation activities of Tamarindus indica seed coat in human fibroblast cells.

Antioxidant activity and total phenolic content of tamarind seed coat extracts (TSCEs) were compared between the two extracts using boiling-water (TSCE-W) and 70% ethanol (TSCE-E) for extraction. TSCE-W, consisting of the highest phenolic content, possessed 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and anti-lipid peroxidation activities much higher than TSCE-E and Trolox. Additionally, both TSCEs also exhibited superoxide anion and hydrogen peroxide scavenging activities higher than Trolox and BHA. Anti-lipid peroxidation and cytotoxicity of TSCE-W were also studied in human foreskin fibroblast CCD-1064Sk cells. Cytotoxic effect was not observed when exposed to TSCE-W up to 1 mg/mL for 12-48 h. However, TSCE-W significantly attenuated lipid peroxidation in H2O2-damaged cells. HPLC analysis showed the presence of (+)-catechin, (-)-epicatechin, and procyanidin B2 in TSCE-W, which could be responsible for antioxidant and anti-lipid peroxidation activities. The results suggest that an inexpensive and simple boiling-water extraction of TSCE-W may provide a valuable natural antioxidant source having anti-lipid peroxidation for health food additives, nutraceuticals as well as cosmeceuticals.

Expression level of pluripotent genes in incomplete reprogramming

OBJECTIVE@#To compare the expression levels of pluripotent genes among incomplete reprogrammed colonies and induced pluripotent stem cells (iPSCs), to explore the relationship between the expression of pluripotent genes and incomplete reprogramming.@*METHODS@#Four genes (Oct4, Sox2, Klf4, C-Myc) were introduced into human foreskin fibroblasts (HFFs) by retroviruses. The HFFs were induced to reprogramming. Different forms of colonies were picked up, analyzed, and compared with iPSCs from different aspects, including the morphology of clones, alkaline phosphatase (AP) staining, immuno-fluorescence, and Q-PCR.@*RESULTS@#In the reprogramming process, different colonies were emerged, some of them exhibited typical human embryonic stem cell morphology (eg., compact colonies, high nucleus-to-cytoplasm ratios, and prominent nucleoli). However, these colonies couldn't maintain these characters after passage. There was an intermediate state, named partially reprogramming. Through analysis and identification, AP staining results were weakly positive, compared with iPSC colonies. The immuno-fluorescence staining demonstrated these colonies just expressed pluripotent protein Oct4. Q-PCR indicated that the expression of exogenous transcription factors was inappropriate, either at a high level or at a low level. Most of the endogenous pluripotency genes were expressed at a low level.@*CONCLUSIONS@#It may be one of the causes of incomplete reprogramming that the exogenous pluripotent gene is low-expressed or over-expressed, and successful reprogramming may depend on a specific stoichiometric balance of Oct4, Sox2, Klf4 and c-Myc.

Keratinized versus non-keratinized preputial flap onlay urethroplasty: does it make any difference in the histological analysis? An experimental study in rabbits

Purpose To compare the histological characteristics of keratinized versus non-keratinized onlay island flaps in an experimental rabbit model. Materials and Methods Sixteen male rabbits were randomly allocated into two experimental groups: keratinized and non-keratinized onlay island flaps. A defect was created in the ventral aspect of the penile urethra. In the keratinized group, a longitudinal island flap was harvested from the external prepuce and rotated to cover the urethral defect. In the non-keratinized group a transverse island flap was harvested from the inner prepuce. The animals were sacrificed after 2, 4, 8 and 12 weeks. Results The flaps were viable in all animals, and no deaths were associated with the procedure. Two urethrocutaneous fistulas were identified, one in each experimental group. A similar pattern of fibrosis was identified in both groups. The keratinized epithelium of the external prepuce kept its histological aspect and keratin production. Both keratinized and non-keratinized groups presented a slight decrease on the epithelial thickness, however without a statistically significant difference between groups. Conclusions In this short-term rabbit model, we observed that the stratified squamous keratinized epithelium from the external prepuce kept its keratin production. There was no statistical influence of the flap type on the mean epithelial thickness. .

Structural alterations of foreskin caused by chronic smoking may explain high levels of urethral reconstruction failure using foreskin flaps

OBJECTIVES: The aim of the present study was to perform a stereological and biochemical analysis of the foreskin of smoker subjects. MATERIALS AND METHODS: Foreskin samples were obtained from 20 young adults (mean = 27.2 years old) submitted to circumcision. Of the patients analyzed, one group (n = 10) had previous history of chronic smoking (a half pack to 3 packs per day for 3 to 13 years (mean = 5.8 ± 3.2). The control group included 10 nonsmoking patients. Masson's trichrome stain was used to quantify the foreskin vascular density. Weigert’s resorcin-fucsin stain was used to assess the elastic system fibers and Picrosirius red stain was applied to study the collagen. Stereological analysis was performed using the Image J software to determine the volumetric densities. For biochemical analysis, the total collagen was determined as µg of hydroxyproline per mg of dry tissue. Means were compared using the unpaired t-test (p < 0.05). RESULTS: Elastic system fibers of smokers was 42.5% higher than in the control group (p = 0.002). In contrast, smooth muscle fibers (p = 0.42) and vascular density (p = 0.16) did not show any significant variation. Qualitative analysis using Picrosirius red stain with polarized light evidenced the presence of type I and III collagen in the foreskin tissue, without significant difference between the groups. Total collagen concentration also did not differ significantly between smokers and non-smokers (73.1µg/mg ± 8.0 vs. 69.2µg/mg ± 5.9, respectively, p = 0.23). CONCLUSIONS: The foreskin tissue of smoking patients had a significant increase of elastic system fibers. Elastic fibers play an important role in this tissue’s turnover and this high concentration in smokers possibly causes high extensibility of the foreskin. The structural alterations in smokers’ foreskins could possibly explain the poor results in smoking patients submitted to foreskin fasciocutaneous flaps in urethral reconstruction surgery.

Neuronal Differentiation of a Human Induced Pluripotent Stem Cell Line (FS-1) Derived from Newborn Foreskin Fibroblasts

Isolation of induced pluripotent stem cells (iPSCs) from fully differentiated somatic cells has revolutionized existing concepts of cell differentiation and stem cells. Importantly, iPSCs generated from somatic cells of patients can be used to model different types of human diseases. They may also serve as autologous cell sources that can be used in transplantation therapy. In this study, we investigated the neuronal properties of an iPSC line that is derived from human neonatal foreskin fibroblasts (FS-1). We initially examined the morphology and marker expression of FS-1 cells at undifferentiated stage. We then spontaneously differentiated FS-1 cells in suspension culture and examined the expression of markers representing three germ layers. We finally differentiated FS-1 cells into neuronal lineages by co-culturing them with PA6 stromal cells, and found that, under the conditions we used, they have a tendency to differentiate into more forebrain-type neurons, suggesting that FS-1 iPSC-derived neural cells will be useful to be used in cell therapy of stroke or Huntington's disease, among others. Taken together, FS-1 cells derived from human neonatal fibroblasts exhibit very similar properties with human ES cells, and can provide useful sources for cell therapy and various other applications.

Long channel technique with pedicle inner preputial flap urethroplasty for middle hypospadias repair / 中华泌尿外科杂志

Objective To investigate the indications and results of long channel technique with pedicle inner preputial flap urethroplasty for middle hypospadias repair. Methods During September 2007 to April 2010,28 cases of middle hypospadias were include in this study.The average age was 2.0 years (1.5 -6.0 years).The orifice of urethra was opened in the shaft of penis,and the distance between the urethral meatus and the center of glans was 25 mm ( 16 - 37 mm).A pars-meatus skin incision was made,which was dissected deep to the urethral plate.The urethral plate was transected,and a long channel between the urethral plate and the corpora cavernosa was created.The neourethra was made from the inner prepuce,and transposed to the ventral tunnel through a tunnel between buck's fascia and albuginea of ventrolateral corpora cavernosa.The neourethra was anastomosed with the proximal urethra.The buck's and dartos fascia along the skin incision were brought together and sutured individually,covering the proximal neo-urethra and the anastomosis.Induced penile erection confirmed that 13 cases were with mild penile curvature,and the other 15 case were without penile curvature.The average length of the defected urethra and tunnel was 38 mm (30 -42 mm) and 33 mm (26 -38 mm). ResultsSuccess was achieved in all cases without fistula or urethral stricture formation with the average follow-up of 20 months (6 -31 months),and penile curvature was completely corrected.The urethra was opened in the apex of the glans with normal-looking circumcised penis. ConclusionsLong channel technique with pedicle inner preputial flap urethroplasty can provide another option for repairing middle hypospadias without penile curvature or with mild penile curvature,especially for young children and those with small penis.This technique is simple,and the result is satisfied.

Foreskin for skin grafting: an unthinkable positive aspect

Background: Penile foreskin is a readily available source of dermis, but it is not often used for skin grafting. Objective: To report the use of the preputial foreskin as donor for full thickness skin grafting. Methods: The preputial foreskin was used as donor for skin grafting in 42 Thai boys. Results: The size of the donor graft obtained varied from 15-50 cm² depending on the patients’s weight and penis size. The grafting was successful in more than 90% of patients. There was less contracture and no limitation of movement when the graft lay over a joint. There were no complications at the donor sites. Conclusion: The use of the preputial foreskin for skin grafting is practical and effective.

Congenital megaprepuce: a new alternative technique for surgical correction

OBJECTIVE: To present a new alternative technique for surgical treatment of congenital megaprepuce. MATERIALS AND METHODS: From April 2004 to April 2006, five patients aged 2 to 5 years were treated using the new technique. The technique is described and illustrated. It differs from other techniques in that it takes into consideration the constant ballooning of the foreskin, which gives to the external genitalia the aspect of a penoscrotal transposition. Cosmetic and functional success were also assessed by a case review. RESULTS: After a follow-up of 1 to 3 years, all patients have normal voiding and a satisfactory cosmetic aspect. CONCLUSION: This new technique could be a useful alternative in treatment of the congenital megaprepuce.

Combined lingual mucosa and buccal mucosa or foreskin urethroplasty for the treatment of long or multi-segment urethral stricture / 中华泌尿外科杂志

Objective To investigate the efficacy and safety of using combined lingual mucosa and buccal mucosa onlay grafts or foreskin flap urethroptasty for the treatment of long or multi-seg-ment urethral strictures. Methods Seven patients with long and 4 cases with multi segment urethral strictures(range 10 to 15 cm,mean 12)underwent substitution urethroplasty using combined lingual mucosa and buccal mucosa onlay grafts or foreskin flap urethroplasty.The patients'age ranged 24 to 56,mean 32 and the course of disease was from 6 to 96 months.Of the 11 patients 7 underwent com-bined lingual mucosa and buccal mucosa grafts urethroptasty,4 patients underwent combined lingual mucosa graft and foreskin flap Urethroplasty. Results The patients were followed up 5-1 2(mean 10)months postoperatively. Meatal stenosis developed 3 months postoperatively in 1 patient who un-derwent combined lingual mucosa and foreskin flap urethroplasty.The patient could void well after re-operation.The other patients could void well and the peak flow rate ranged from 2 1 to 3 6 ml/s(mean 26.8 ml/s). Conclusions Combined lingual mucosa and buccal mucosa onlay grafts or foreskin flap substitution urethroplasty may have the advantage of easier harvest,less trauma.It could be a good U- rethral substitution technique for the treatment of long or multi-segment urethral stricture.

Biologic characters of human foreskin fibroblasts / 重庆医科大学学报

Objective:To study the biologic characters of human foreskin fibroblasts(HFF)to lay the foundation for a long-term culture for human embryonic germ cells in vitro.Methods:The method of separating HFF was investigated.By immunocytochemical method,MTT and flow cytometry,we investigated the morphology and the purity of HFF,study the cell growth curve and cell cycle of HFF,and the effects of different concentrations of mitomycin on growth of HFF at different times.Results:Epidermis and dermis were more easily separated after overnight digestion(12~16 h)in 0.25% Trypsin at 4℃,compared with incubation for 2 h in 5% CO2 at 37℃.Vimentin was strongly positive stained with the purity of 95 percent.There was no obvious stranded period.The rapid proliferation period was in 1~6 d of cell growth curve.The platform stage began at 7 d.Majority of the cells were in G1/G0 phases.The cell cycle corresponded to cell growth curve.Mitomycin C(MMC)inhibited the proliferation of HFF at 12.5 ?g/ml over 2.5 h of MMC treatment.Conclusion:Its biological characters showed that HFF can be used as feeder layer for in-vitro cultured human embryonic germ cells。