Keqin Zhang

Relationship Between Patient Age and Superficial Transitional Cell Carcinoma Characteristics

OBJECTIVES To evaluate the relationship between patient age and the characteristics of superficial transitional cell carcinoma. METHODS The clinical and pathologic records of 576 patients were retrospectively reviewed. The patients were classified into three groups: those 40 years or younger, those 41 to 59 years old, and those 60 years or older. The transitional cell carcinoma characteristics of three groups were analyzed to define the relationship, if any, with age. RESULTS The male/female ratio was 4.1:1, 3.6:1, and 2.3:1 in the three age groups, with significant differences between the 60 years or older group and the 40 years or younger group and 41 to 59 year group (P <0.05). The percentage of patients with poorly differentiated tumor increased with increasing age, and a significant difference was found between the 60 years or older group and the 40 years or younger and 41 to 59 year groups (P <0.05). The overall recurrence rate was 34.2% at 12 months and 40.8% at 24 months. The nonrecurrence rate was significantly greater in those 40 years or younger compared with those 60 years or older in all three risk groups (P <0.05). CONCLUSIONS The results of our study have shown that the percentage of female patients with bladder cancer increases with increasing age and that elderly patients are more likely to present with poorly differentiated bladder cancer. Also, the recurrence-free survival rate decreased with increasing age.

Bone Marrow Mesenchymal Stem Cells Induce Angiogenesis and Promote Bladder Cancer Growth in a Rabbit Model

Objectives: To investigate the effect of mesenchymal stem cells (MSCs) in the process of tumor development and the possibility of MSCs differentiating into vascular endothelial cells in the tumor microenvironment. Material and Methods: Twenty male New Zealand rabbits were randomly divided into 2 groups: a test group and a control group. MSCs were isolated and cultured by bone marrow cell adherence. The bladder tumor models were built by embedding a VX2 mass in swelled bladder mucosa in all of the rabbits (n = 20). One week later, 4′,6-diamidino-2-phenylindole-labeling MSCs were transplanted into tumor tissue in the test group (n = 10). Culture medium was injected into the tumor tissue of the control group (n = 10). The maximum diameter of the tumor mass was measured by ultrasound at 2 and 4 weeks after the VX2 tumor mass was embedded. All animals were sacrificed at 4 weeks. The double labeling immunofluorescence for CD146 was performed to reveal whether engrafted cells can differentiate into vascular endothelial cells. Vascular density was compared between the 2 groups. Results: There was no significant difference in the maximum diameters of the tumor masses between the 2 groups at 2 weeks (test group 0.77 ± 0.15 cm vs. control group 0.71 ± 0.15 cm, p > 0.05). The maximum diameters appeared larger in the test group at 4 weeks (test group 3.82 ± 0.94 cm vs. control group 2.28 ± 0.54 cm, p < 0.05). Immunofluorescence studies revealed some engrafted MSCs expressing a vascular endothelial cell phenotype (CD146). Furthermore, vascular density was augmented in the test group in comparison to the control group (10.1 ± 0.70/0.2 mm2 vs. 8.24 ± 0.81/0.2 mm2, p < 0.05). Conclusions: Engrafted MSCs can differentiate into vascular endothelial cells and contribute to angiogenesis in the tumor microenvironment, which may be the major pathway of promoting tumor growth.

Are TGF-β1 and bFGF Correlated with Bladder Underactivity Induced by Bladder Outlet Obstruction?

Background: Transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (bFGF) are the two most important growth factors that have been found. Previous studies have indicated that the above two factors play an important role in the physiological growth, response to injury and the following fibrous proliferation of the bladder. Therefore, they may be related to the detrusor underactivity due to bladder outlet obstruction (BOO). The aim of this study is to investigate the relationship between them. Materials and Methods: 29 evaluable Wistar rats were divided into three groups: control group, BOO 2 weeks group and BOO 6 weeks group. After successful models, we measured excised bladder mass, detrusor contraction force (DCF) in vitro stimulated by carbachol of four different concentrations (10–5, 10–4, 10–3 and 10–2 mM). Simultaneously, the expression of TGF-β1 mRNA and bFGF mRNA in detrusor specimens was detected by reverse transcription polymerase chain reaction (RT-PCR) analysis. Additionally, we analyzed the correlation between DCF and the detrusor mRNA expression of the two factors to determine whether they are associated with the detrusor contraction response when BOO occurs. Results: Bladder mass increased steadily and significantly with the progression of the BOO. While at the point of 10–4 and 10–3 mM carbachol concentration, DCF in the BOO 2 weeks group was higher, no significant differences were found at the point of 10–5 and 10–2 mM carbachol concentration when compared to the control group. DCF was found to be significantly lower in the BOO 6 weeks group than in the BOO 2 weeks group and control group at all points of carbachol concentration. TGF-β1 mRNA expression of the detrusor was found to be higher only in BOO 6 weeks. However, there was a steady and significant increase of bFGF mRNA expression with the aggravation of BOO. Correlation analysis demonstrated that there was a significant moderate negative correlation between DCF in vitro and the level of TGF-β1 mRNA. Meanwhile, a significant high negative correlation was acquired between the DCF and bFGF mRNA level. Conclusion: DCF in the severe BOO group is remarkably impaired. There is a sustained rise of bFGF mRNA expression in detrusor with the progression of BOO, but TGF-β1 mRNA expression increase becomes evident only in the decompensation stage. Significant negative correlations are found between DCF in vivo and the expression of TGF-β1 mRNA, bFGF mRNA. Additionally, DCF correlates negatively with the bladder mass statistically after BOO.

Probucol Improves Erectile Function by Restoring Endothelial Function and Preventing Cavernous Fibrosis in Streptozotocin-induced Diabetic Rats

OBJECTIVE To investigate the effects of probucol on erectile function in streptozotocin-induced diabetic rats and explore the underlying mechanisms. METHODS A total of thirty 12-week-old Sprague-Dawley male rats received a 1-time intraperitoneal streptozotocin (60 mg/kg) or vehicle injection after a 12-hour fast. Three days later, the streptozotocin-induced diabetic rats were randomly divided into 2 groups and were treated with daily gavage feedings of probucol at doses of 0 and 500 mg/kg for 12 weeks. A positive control group underwent intraperitoneal injection of saline followed by daily gavage of saline solution. Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated using immunohistochemistry, Western blot, and ELISA to assess the protein arginine-N-methyltransferase 1/dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine/nitric oxide synthase metabolism pathway. Superoxide dismutase activity and malondialdehyde levels were detected by colorimetry. We also evaluated penile histological changes such as smooth muscle contents and Massons trichrome stain. RESULTS Significant recovery of erectile function was observed in the probucol-treated rats than the untreated diabetic rats. The protein expression of dimethylarginine dimethylaminohydrolase and nitric oxide synthase, cyclic guanosine monophosphate concentrations, and superoxide dismutase activity in cavernous tissue of probucol-treated rats were significantly higher than the untreated diabetic rats. The protein expression of protein arginine-N-methyltransferase 1, asymmetric dimethylarginine concentrations, and malondialdehyde levels in cavernous tissue of probucol-treated rats were significantly lower than the untreated diabetic rats. In addition, probucol treatment markedly augments the cavernous smooth muscle content. CONCLUSION Probucol treatment improves erectile function by restoring endothelial function and preventing cavernous fibrosis in streptozotocin-induced diabetic rats.

Plasmakinetic Vapor Enucleation of the Prostate with Button Electrode versus Plasmakinetic Resection of the Prostate for Benign Prostatic Enlargement >90 ml: Perioperative and 3-Month Follow-Up Results of a Prospective, Randomized Clinical Trial

Objective: To evaluate plasmakinetic vapor enucleation of the prostate (PVEP) with button electrode and plasmakinetic resection of the prostate (PKRP) in patients with urinary symptoms due to benign prostatic enlargement (BPE) >90 ml. Methods: A total of 112 patients with symptomatic BPE were randomly assigned to either PKRP or PVEP prospectively from August 2012 to May 2014 in our department. Perioperative and postoperative data were investigated during a 3-month follow-up. Results: PVEP was significantly superior to PKRP in terms of operation time (63.9 ± 7.7 vs. 78.1 ± 13.6 min, p < 0.001), hemoglobin loss (1.18 ± 0.30 vs. 1.63 ± 0.38 g/dl, p < 0.001), serum sodium decrease (2.9 ± 0.7 vs. 4.3 ± 0.8 mmol/l, p < 0.001), catheterization duration (49.3 ± 12.2 vs. 78.1 ± 14.8 h, p < 0.001) and hospital stay (100.2 ± 28.3 vs. 116.0 ± 29.2 h, p = 0.004). There were no statistical differences in blood transfusion between the two groups. In addition, there were no statistical differences in maximum urinary flow rate, International Prostate Symptom Score, postvoid residual urine volume, quality-of-life score, transient incontinence, and urethral stricture at 3 months postoperatively. Conclusions: PVEP with button electrode is an equally effective technique for treatment of large BPE with PKRP, with more safety and faster recovery. It may become the superior alternative to PKRP for patients with large BPE.

Epigallocatechin-3-gallate ameliorates erectile function in aged rats via regulation of PRMT1/DDAH/ADMA/NOS metabolism pathway.

Aging-related ED is predominantly attributed to neurovascular dysfunction mediated by NO suppression and increased oxidative stress in penis. The alterations of protein arginine methyltransferases 1 (PRMT1)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetrical dimethylarginine (ADMA)/NO synthase (NOS) pathway regulate NO production in the vascular endothelium. Epigallocatechin-3-gallate (EGCG) is one of the most abundant and antioxidative ingredients isolated from green tea. In the present study, 40 Sprague-Dawley rats were randomly distributed into four groups: one young rat group and three aged rat groups treated with daily gavage feedings of EGCG at doses of 0, 10 mg kg−1 and 100 mg kg−1 for 12 weeks, respectively. Erectile function was assessed by electrical stimulation of the cavernous nerves with intracavernous pressure (ICP) measurement. After euthanasia, penile tissue was investigated using Western blot and ELISA to assess the PRMT1/DDAH/ADMA/NOS metabolism pathway. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected by colorimetry. We also evaluated smooth muscle contents. The ratio of maximal ICP and mean systemic arterial pressure (MAP) was markedly higher in EGCG-treated aged rats than in untreated aged rats. We found that DDAH1 and DDAH2 were expressed in cavernosal tissue, and they were downregulated in corpora of aged rats. The administration of EGCG upregulated the expression and activity of DDAH. In contrast, EGCG treatment downregulated the expression of PRMT1 and ADMA content. Moreover, EGCG-treated rats showed an improvement in smooth muscle expression, the ratio of smooth muscle cell/collagen fibril, SOD activity, and MDA levels when compared with untreated aged rats.

Effect of DDAH/ADMA/NOS regulation pathway on cavernae corporum cavernosorum rat penis of different age

The effect of DDAH/ADMA/NOS pathway in penile tissue of rats of different age was investigated to better understand the mechanism of age‐related erectile dysfunction (ED). The Sprague Dawley male rats were assigned as the young group (3 month old, n = 10) and the old group (18 month old, n = 10) respectively. Intracavernous pressure (ICP) was measured before and after papaverine intracavernous injection. Pathology structure of penile tissue was evaluated under transmission electron microscope. The expression amounts of asymmetric dimethylarginine (ADMA) and cyclic guanosine monophosphate (cGMP) in penile tissue were detected by ELISA; the expression levels of isoform‐specific DDAH and NOS were assessed via Western blot. Compared with the young group, the ICP in the old group rat decreased significantly (33.46 ± 5.37 versus 39.71 ± 3.67 mmHg, P = 0.02) after papaverine injection. Diffused fibrosis and impairment of endothelial cell were observed in corpus cavernosum in the old group rats. Higher level of ADMA (10.83 ± 0.96 versus 7.51 ± 1.39 μmol per gpro, P = 3.14 × 10−4) and lower level of cGMP (29.42 ± 3.84 versus 47.09 ± 6.07 nmol per gpro, P = 1.57 × 10−6) were detected in penile tissue of the old group compared with those of the young group. Expression of DDAH1, DDAH2, endothelial NOS (eNOS) and neuronal NOS(nNOS) all decreased significantly in penile tissue of the old group rat. The DDAH/ADMA/NOS regulation pathway changes dramatically accompanying with lower ICP in old group rat compared with those of the young group. Such findings in rats are suggestive in understanding the mechanism of age‐related ED in humans.

Clinical Significance of Urodynamic Analysis in Patients with Benign Prostatic Enlargement Complicated with Diabetes Mellitus

Aim: To compare the bladder dysfunction associated with benign prostatic enlargement (BPE) in patients with and without diabetes mellitus (DM) by urodynamic study. Materials and Methods: The records of 166 first-visit BPE patients were reviewed. Patients were divided into two groups: concomitant group (CG) – 74 patients with BPE complicated with DM, and single group (SG) – 92 isolated BPE patients. Urodynamic findings of the two groups were analyzed. Results: In the clinical data, increased postvoiding residual urine volume (PVR) appeared more often in CG (p < 0.05). In the urodynamic findings, significantly higher maximum cystometric capacity (MCC), incidence of impaired bladder sensation, bladder compliance and detrusor overactivity existed in CG (p < 0.05). In addition, the maximum detrusor pressure during voiding (Pdetmax) and the incidence of bladder outlet obstruction (BOO) were significantly higher in SG (p < 0.05). Conclusions: Impaired bladder function is more severe in patients with BPE complicated with DM than those isolated BPE patients. Urodynamic study can provide objective data on diagnosis of voiding dysfunction in BPE patients with and without DM, and it is helpful for doctors to choose better clinical intervention.

Hypoxia-induced apoptosis and mechanism of epididymal dysfunction in rats with left-side varicocele

To investigate the relationship between hypoxia and epididymal dysfunction and the mechanism of epididymal dysfunction in rats with left‐side varicocele, a total of 45 male Wistar rats were randomly divided into three groups in average. The expression of hypoxia‐inducible factor‐1α (HIF‐1α) was detected by Western blot and immunohistochemical analysis respectively. HIF‐1α was expressed in the experimental group, and the positive rate was significantly higher than that of either the sham or the control group (P < 0.05). The apoptosis index (AI) of epididymal epithelium was higher in the experimental group (7.25 ± 2.56) than that in either the sham (0.52 ± 0.57, P < 0.01) or the control group (0.08 ± 0.13, P < 0.01). Additionally, the levels of sialic acid and carnitine were lower in the experimental group than that in either the sham or the control group (P < 0.05) and were significantly negatively correlated with HIF‐1α expression (r = −0.620, P = 0.014, and r = −0.610, P = 0.016 respectively). It is concluded that left‐side varicocele could cause epididymal hypoxia and epididymal dysfunction. Moreover, HIF‐1α maybe act as useful factor to predict germ cell apoptosis in varicocele.

Mesenchymal Stem Cells Promote Tumor Progression via Inducing Stroma Remodeling on Rabbit VX2 Bladder Tumor Model

Background and aim: Mesenchymal stem cells (MSCs) are capable of impacting tumor progression but its role in tumor stroma remodeling still remains unclear. This present study was aimed to evaluate the potential function of MSCs on tumor stroma remodeling using rabbits VX2 bladder tumor model. Methods: The VX2 bladder tumor models were established by injecting mixed cell suspensions (106 of VX2 tumor cells and 0/106/107 of autologous MSCs in group A, B, C, respectively) into the bladder mucosa using thirty male New Zealand white rabbits. The tumor volume was measured by ultrasound at the time points of 1st, 2nd, 3rd and 4th week after inoculation. At the end of the fourth week, the tumor tissue expressions of basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGFβ-1), hepatocyte growth factor (HGF), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) were determined using Real-time quantitative PCR and immunohistochemistry. Masson trichrome staining and Cy3-FITC double-labelled immunofluorescence staining were used to determine the MSCs distribution in tumor tissue in another two rabbits implanted with a cell suspension of 106 VX2 tumor cells and 106 autologous MSCs. Results: MSCs were homogeneously distributed in tumor tissues after 7 days of inoculation, which were not consistent with the distribution of tumor stroma. After 21 days of inoculation, MSCs have been integrated into tumor interstitial tissue and mainly distributed in the mesenchyma around the tumor nest. At the 1st, 2nd, 3rd and 4th week time point, tumor volume in group A < group B < group C, and the difference has statistical significance (all p<0.001).The relative mRNA and protein levels of bFGF, TGFβ-1 and HGF were significantly higher in group B and C compared with group A (all p<0.05), as well as the mRNA levels of bFGF, HGF were higher in group C than group B (p<0.05), and the protein levels of bFGF, TGFβ-1 were higher in group C than group B (p<0.05). The mRNA and protein levels of MMP2 were significantly higher in group B, C than group A (p<0.05). MMP9 was increasingly over expressed along with the growing amount of MSCs inoculated within tumor, both at the level of mRNA and protein (all p<0.05). Conclusion: MSCs participate in tumor stroma remodeling via inducing overexpression of some important growth factors and MMPs.