Xiang-An Tu

Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction

The ability to identify and isolate lineage-specific stem cells from adult tissues could facilitate cell replacement therapy. Leydig cells (LCs) are the primary source of androgen in the mammalian testis, and the prospective identification of stem Leydig cells (SLCs) may offer new opportunities for treating testosterone deficiency. Here, in a transgenic mouse model expressing GFP driven by the Nestin (Nes) promoter, we observed Nes-GFP+ cells located in the testicular interstitial compartment where SLCs normally reside. We showed that these Nes-GFP+ cells expressed LIFR and PDGFR-α, but not LC lineage markers. We further observed that these cells were capable of clonogenic self-renewal and extensive proliferation in vitro and could differentiate into neural or mesenchymal cell lineages, as well as LCs, with the ability to produce testosterone, under defined conditions. Moreover, when transplanted into the testes of LC-disrupted or aging models, the Nes-GFP+ cells colonized the interstitium and partially increased testosterone production, and then accelerated meiotic and post-meiotic germ cell recovery. In addition, we further demonstrated that CD51 might be a putative cell surface marker for SLCs, similar with Nestin. Taken together, these results suggest that Nes-GFP+ cells from the testis have the characteristics of SLCs, and our study would shed new light on developing stem cell replacement therapy for testosterone deficiency.

Long-term sexual activity status and influencing factors in men after surgery for hypospadias.

The aim of this study was to compare the long-term postoperative status of hypospadiac patients by analysing their sexual psychology, sexual behaviour, sexual function and influencing factors. A total of 130 hypospadiac patients hospitalized between January 1988 and December 2007 were followed up with questionnaires using Zungs Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), a self-designed sexual function questionnaire and a 5-item version of the International Index of Erectile Function (IIEF-5). The surveys served to evaluate the effects of hypospadias type, number of operations and surgical procedures on sexual psychology, sexual behaviour and sexual function. The control group consisted of 50 healthy adults. The postoperative SDS / SAS scores and occurrences of depression/anxiety in hypospadiac patients were significantly higher than those of normal controls (P < 0.001). Patients with proximal hypospadias and multiple procedures differed from those with distal hypospadias and a single procedure in all parameters of sexual psychology (P < 0.05). The average penile lengths and circumferences of hypospadiac patients under either erect or flaccid conditions were significantly shorter than those of normal controls (P < 0.001). A similar difference existed between patients with distal and proximal hypospadias (P < 0.01). There was no significant difference in any parameter of sexual function between patients with different numbers of operations and surgical procedures. Hypospadiac patients were clearly impaired in sexual psychology and penile development. The severity of hypospadias and number of operations were key factors that influenced the sexual psychology of patients. This finding indicated the importance of long-term follow-up and psychological counselling for hypospadiac patients postoperatively.

Insulin resistance is an independent determinate of ED in young adult men.

Background Insulin resistance (IR) triggers endothelial dysfunction, which contributes to erectile dysfunction (ED) and cardiovascular disease. Aim To evaluate whether IR was related to ED in young adult patients. Methods A total of 283 consecutive men complaining of ED at least six months were enrolled, with a full medical history, physical examination, and laboratory tests collected. Quantitative Insulin Sensitivity Check Index (QUICKI) was used to determine IR. The severity of ED was assessed by IIEF-5 questionnaire. Endothelial function was assessed by ultrasonographic examination of brachial artery flow mediated dilation (FMD). Results IR was detected in 52% patients. Subjects with IR had significant higher total cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-c), glycated haemoglobin (HBA1c), high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI), but showed significant lower IIEF-5 score, FMD%, high density lipoprotein -cholesterol (HDL-c), testosterone, sex hormone binding globulin (SHBG) levels than patients without IR. Multiple regression analysis showed QUICKI and testosterone were independent predictors of IIEF-5 score. Furthermore, the incidence of IR was correlated with the severity of ED. Conclusions Compared with other CVFs, IR was found as the most prevalent in our subjects. Besides, IR was independently associated with ED and its severity, suggesting an adverse effect of insulin resistance on erectile function.

Psychosexual adjustment and age factors in 130 men undergone hypospadias surgery in a Chinese hospital.

The study investigated the psychosexual status and sexual function in adults who had hypospadias surgery at different ages. A detailed questionnaire was mailed to 130 patients who underwent hypospadias surgery between January 1988 and December 2007, and 50 healthy males who served as the control group. The patients were divided into three groups based on their age at which surgery was completed: group A (n = 32; <10 years); group B (n = 45; 10–18 years); and group C (n = 53; >18 years). The Zung Self‐Rating Anxiety Scale and The Zung Self‐Rating Depression Scale were used to assess psychosexual status; a designed questionnaire and the International Index of Erectile Function‐5 were used to assess sexual function. The incidence of anxiety and depression was significantly higher in patients than that in controls (P < 0.001), and was correlated with the age at which surgery was completed. The length and circumference of penises in patients were shorter than those of control groups with statistically significant differences (P < 0.01). There were no significant differences between patients and controls regarding libido strength, overall sexual satisfaction and erectile function (P > 0.05). In conclusion, difference existed in certain aspects of psychosexual and penile development between patients and controls. Hypospadias surgery should be performed early.

The expression and role of tyrosine kinase ETK/BMX in renal cell carcinoma.

BackgroundExpression of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors, but the underlying molecular mechanisms and its clinical significance in renal cell carcinoma (RCC) remain to be elucidated.MethodsETK expression in 90 human RCC and 30 human normal renal tissue samples was examined by immunohistochemistry and compared with several clinicopathologic parameters. To further demonstrate the biological function of ETK in RCC, Western blot was used to test the expression level of ETK protein in RCC cell lines. Subsequent to the downregulation of ETK by small interfering RNA, the effects of ETK on RCC cell growth, apoptosis, migration and invasion were assessed by methyl thiazol tetrazolium assay, flow cytometry and transwell assay. And the varying expression of VEGF, STAT3 and phosphorylated STAT3 (p-STAT3) in RCC were evaluated by Western blot.ResultsImmunohistochemistry analysis showed that ETK expression was highly increased in RCC and was positively correlated with clinical stage, grade and metastasis. Simultaneously, the overall survival time in patients with higher ETK expression was obviously shorter than that in patients with lower ETK expression. ETK was also detected in RCC cell lines. Moreover, the down-regulating ETK significantly inhibited RCC cell growth, migration, invasion and promoted apoptosis. The expression of VEGF and p-STAT3 were also decreased.ConclusionsOur study suggests that the overexpression of ETK is associated with the malignancy and disease progression of RCC. Since ETK is also involved in RCC cell biological function and VEGF-ETK-STAT3 loop, ETK may be used as a potential therapeutic target for RCC.

Was Fine-Needle Vasography an Obsolete Diagnostic Method to Evaluate Ejaculatory Duct Obstruction? Report of 37 Cases

Objectives: Based on comparative analyses of the precision as well as reliability of the diagnostic results on fine-needle vasography (FNV) and transrectal ultrasonography (TRUS) in the diagnosis of patients who were suspected of having ejaculatory duct obstruction (EDO), this paper aims to demonstrate whether or not FNV techniques still constitute the backbone of diagnostic imaging used in obstructive azoospermia of EDO. Materials and Methods: From July 2005 to December 2008, opening fine-needle punctuation and vasography were performed under local anesthesia in 37 infertile male patients in our center, all of whom were suspected of having bilateral EDO. The diagnostic criteria of these infertile males included characteristic changes of TRUS and/or characteristic changes of semen analysis. Comparative analyses were made of the diagnostic results of the two methods. Results: In the 37 male patients, 19 (51.35%) had been confirmed with pathognomonic findings of both semen analyses and TRUS on complete EDO. Of the others, 18 patients (48.65%) testified with only pathognomonic findings of TRUS but not the typical characteristics on semen analyses. When compared with diagnostic results via FNV however, there were only 5 patients (13.51%) who could be confirmed as having bilateral EDO, 16/37 showed obstruction of the epididymis and proximal vas deferens, 7/37 showed bilateral vasal multiple obstruction, 2 showed unilateral EDO and multiple obstruction of the contralateral vas deferens, and the other 6 patients showed unilateral vasal multiple obstruction and obstruction on the contralateral epididymis and proximal vas deferens. Free flow of the contrast medium could be defined into the bladder by vasography in 23 patients. Of the 23 patients, 12 were suspected of having delayed evacuation based on more than 50% contrast medium remaining inside their seminal vesicles after exhaustion of urine. Conclusion: Our analyses suggest that despite its advantages of being non-invasive, the diagnostic effect of TRUS is limited by both accuracy and reliability. In contrast, although an invasive radiographic imaging method, FNV has been proven as being informative when providing preoperative details about obstruction and other symptoms. After 3 years of research we came to the conclusion that opening fine-needle punctuation and vasography have not become outdated, at least recently, and will remain a necessary and effective method to identify diseases and to provide a strictly defined morphology of the seminal vesicle and ductal system for more comprehensive diagnosis of obstructive azoospermia of EDO.

Erectile Dysfunction in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Outcomes from a Multi-Center Study and Risk Factor Analysis in a Single Center

The aim of this study was to investigate the prevalence of erectile dysfunction (ED) in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and explore the influence of UPOINT domains, National Institutes of Health-CP symptom index (NIH-CPSI) and other factors on ED prevalence. This was a prospective study of consecutive patients with CP/CPPS seen at 11 tertiary hospitals during January–July 2014. ED was diagnosed as a score of<21 on the International Index of Erectile Function (IIEF-5). Patients from one center were evaluated by the UPOINT system and NIH-CPSI. Each patient was assessed using clinical examination, asocio-demographic questionnaire, the Patient Health Questionnaire (PHQ), the Pain Catastrophizing Scale (PCS), NIH-CPSI and IIEF-5.1406 patients from 11 centers (mean age, 32.18 years; range 18–60 years) were enrolled. ED was found in 638/1406 patients (45.4%), and was categorized as mild in 291(45.6%), moderate in 297(46.6%) and severe in50(7.7%). 192 patients from one center(mean age,31.3 years; range 18–57 years) were further studied.IIEF-5 score correlated negatively with NIH-CPSI(r = 0.251), PHQ (r = 0.355) and PCS (r = 0.322)scores (P<0.001).PHQ score correlated positively with NIH-CPSI (r = 0.586) and PCS(r = 0.662) scores (P<0.001).NIH-CPSI, PHQ, PCS and IIEF-5 scores did not differ significantly between class IIIA and IIIB CP/CPPS. Multivariate logistic regression showed that UPOINT psychological (P) domain and NIH-CPSI symptom severity were independent risk factors for ED in CP/CPPS. It is concluded that psychological factors and symptom severity are independent risk factors for ED in CP/CPPS.

Mucormycosis extending from the surgical wound to the transplanted kidney: case report and literature review.

Mucormycosis is an opportunistic, life-threatening infection in organ transplant recipients. We report a case of surgical wound mucormycosis that extended to a transplanted kidney. The patient was a 59-year-old man who underwent a donation-after-cardiac-death kidney transplant 10 years after receiving a liver transplant. On day 10 after the kidney transplant, he presented with cutaneous and subcutaneous tissues necrotizing at his right lower abdominal surgical wound. The necrotic tissue biopsy and laboratory culture showed different causes, while a polymerase chain reaction quickly identified the causative fungus at the species level. Although the combination therapy consisted of immunosuppressant withdrawal, intravenous Liposome AmB, and aggressive surgical debridement; unfortunately, the cutaneous mucormycosis invaded his transplanted kidney, and the patient was given a graft nephrectomy and subsequent hemodialysis. We review the literature and conclude that mucormycosis in organ transplant recipients is a rare and extremely severe complication. Polymerase chain reaction provides a rapid and accurate diagnostic technique for species identification. Early effective antifungal therapy combined with aggressive surgical intervention and judicious withdrawal of immunosuppressants appears to be indispensable for a favorable outcome.

Percutaneous ultrasound-guided radiofrequency ablation treatment and genetic testing for renal cell carcinoma with Von Hippel-Lindau disease.

Percutaneous ultrasound-guided radiofrequency ablation is increasingly being studied in the treatment of renal tumors. Because percutaneous ultrasound-guided radiofrequency ablation is a minimally invasive and nephron-sparing procedure, it is ideally suited for patients with a single kidney, multiple tumors, or contraindications to conventional surgery. We report on a patient with Von Hippel-Lindau (VHL) disease who had multicentric tumors in the single kidney that was successfully treated with percutaneous ultrasound-guided radiofrequncy ablation. The one-year follow-up showed that there was no local recurrence or metastasis. And genetic testing showed the patient had a T to G heterozygotic missense mutation at nucleotide 515 of VHL gene exon 1.

Screening and identification of a renal carcinoma specific peptide from a phage display peptide library

BackgroundSpecific peptide ligands to cell surface receptors have been extensively used in tumor research and clinical applications. Phage display technology is a powerful tool for the isolation of cell-specific peptide ligands. To screen and identify novel markers for renal cell carcinoma, we evaluated a peptide that had been identified by phage display technology.MethodsA renal carcinoma cell line A498 and a normal renal cell line HK-2 were used to carry out subtractive screening in vitro with a phage display peptide library. After three rounds of panning, there was an obvious enrichment for the phages specifically binding to the A498 cells, and the output/input ratio of phages increased about 100 fold. A group of peptides capable of binding specifically to the renal carcinoma cells were obtained, and the affinity of these peptides to the targeting cells and tissues was studied.ResultsThrough a cell-based ELISA, immunocytochemical staining, immunohistochemical staining, and immunofluorescence, the Phage ZT-2 and synthetic peptide ZT-2 were shown to specifically bind to the tumor cell surfaces of A498 and incision specimens, but not to normal renal tissue samples.ConclusionA peptide ZT-2, which binds specifically to the renal carcinoma cell line A498 was selected from phage display peptide libraries. Therefore, it provides a potential tool for early diagnosis of renal carcinoma or targeted drug delivery in chemotherapy.