Search

Objective To compare the clinical symptoms, brain copper deposition changes of Meso-2,3-dimercaptosuccinic acid (DMSA) and penicillamine therapy in patients with Wilson disease (WD) within 2 years. Methods 68 drug-naive patients with WD were enrolled. 10 WD patients treated with zinc gluconate alone were used as the control group. Neurological symptoms were scored using the modified Young Scale. Liver function tests, copper indices and sensitive weighted imaging (SWI) examination were collected. The values of corrected phase (CP) were collected. WD patients were treated with DPA (group 1) or DMSA (group 2) for two years, and followed up every 2 months. Results The ratio of neurological improvement in group 2 was higher than that in group 1 (P = 0.029). Higher rate of neurologic worsening was noticed in patients treated with DPA vs DMSA (P = 0.039). The post-treatment neurological score of DMSA group was lower than that of Zn group (P = 0.037). Hepatic function in 63.3% of patients was stable, while 16.7% was improved, and 20% was deteriorated, after DMSA therapy. Urinary copper levels were lower 1 month (p = 0.032), 4 months (p = 0.041), 12 months (p = 0.037) after initiation of treatment in group 2 than in group 1. At the first year of treatment, the CP values in globus pallidus and substantia nigra in group 2 were higher than those in group 1 (P = 0.034,0.039). At the second year of treatment, the CP values of substantia nigra in group 2 were higher (P = 0.041). Discontinuation was more common in patients on DPA therapy (P = 0 0.032). Conclusions DMSA could remove metal from brain tissue faster than DPA. DMSA is effective for neurologic symptoms, while the outcome for hepatic symptoms is not entirely satisfactory. DMSA therapy is better tolerated than DPA.

A randomized-controlled trial comparing study of the changes in brain sensitive-weighted imaging (SWI) of Wilson disease (WD) patients during the treatment with metal chelator was done. 100 untreated WD patients (80 cases of cerebral type, 20 cases of hepatic type, age 20.13 ± 9.12 years old) and 20 normal controls were selected. Neurological symptoms were scored using the modified Young scale. Liver function tests and copper indices were collected. All study objects received SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. Cerebral-type WD patients were treated with D-penicillamine (DPA) (group 1) or Dimercaptopropane Sulfonate (DMPS) + Dimercaptosuccinic Acid (DMSA) (group 2). Hepatic-type WD patients were treated with DPA (group 3). All patients received annual neurological symptom score, liver function, copper indices, and SWI examination. At the first year of treatment, score of the modified Young scale in group 2 was lower than that in group 1 (P = 0.023) and lower than that before treatment (P = 0.040). After 2 years of treatment, the score of the modified Young scale in group 1 was lower than that before treatment (P = 0.012). At the second year after treatment, the urinary copper in group 2 was higher than that in group 1 (P = 0.014). Urinary copper was maintained at 200 µg/day in group 1 and 300 µg/day in group 2 after 3 years of treatment. At the first year of treatment, serum copper in group 1 was lower than that in group 2 (P = 0.032). At the first year of treatment, CP values of the pallidum and substantia nigra in group 2 were higher than those in group 1 (P = 0.026, 0.040). At the second year of treatment, CP value of substantia nigra in group 2 was higher than that in group 1 (P = 0.037). After 3 years of treatment, there was no difference in CP values between WD patients and normal controls. Therapy with DMPS and DMSA improves neurological symptoms of WD patients more quickly and leads to less aggravation, compared with therapy with DPA. The metal content in the brain of WD patients was at a low level after 3 years of treatment. DMPS and DMSA can remove metal from brain tissue faster than DPA.

Objective To evaluate different injury factors and pathological characteristics of the brain at different disease stages in toxic milk (TX) mice, an animal model of Wilson's disease (WD). Methods Thirty TX mice (10 each at 3, 6 and 12 months old) and 30 age‐matched C57 mice were used in this study. Corrected phase (CP) values were determined from susceptibility‐weighted images. Myelin content was determined by measuring inhibition optical density values of Luxol fast blue‐stained sections. Neurofilament protein 68 kDa (NF68), β‐amyloid precursor protein (β‐APP), and myelin basic protein (MBP) levels, as well as copper and iron content, in brain nuclei of the TX mouse were evaluated. Gene amplification ratios for catalase (CAT), GSH peroxidase (GSH‐PX), nitric oxide synthase (NOS), and superoxide dismutase (SOD) in mouse brain were also determined. Results Compared with C57 mice, neuronal cell counts were decreased in 12‐months‐old TX mice (p = .011). Myelin content was decreased in the lenticular nucleus (p = .029), thalamus (p = .030), and brainstem (p = .034) of 6‐months‐old TX mice; decreases in the corresponding nuclei (p = .044, .037, and .032, respectively) were also found in 12‐months‐old TX mice. MBP values were lower in the lenticular nucleus and thalamus (p = .027 and .016, respectively) of 6‐months‐old TX mice and in the corresponding nuclei (p = .24 and .040) of 12‐months‐old TX mice. NF‐68 values were lower in the lenticular nucleus and thalamus (p = .034 and .037, respectively) of 6‐months‐old TX mice and in the corresponding nuclei (p = .006 and .012) of 12‐months‐old TX mice. β‐APP values were higher in the thalamus of 6‐months‐old (p = .037) and 12‐months‐old (p = .012) TX mice. Iron content was higher in the lenticular nucleus, thalamus, and cerebellum (p = .044, .038, and .029, respectively) of 6‐months‐old TX mice and in the corresponding nuclei (p = .017, .024, and .029) of 12‐months‐old TX mice. The NOS gene amplification multiple was higher (p = .039), whereas the SOD1 gene amplification multiple was lower (p = .041) in 12‐months‐old TX mice. There was no correlation between metal content or oxidation index and pathological index. Conclusions The pathological characteristics of the brains of TX mice may differ at different ages. Different pathogenic factors, including copper and iron deposition and abnormal oxidative stress, are present at different stages., The brain pathological characteristics of toxic milk (TX) mice at different age of months may be different. Both copper and iron deposition, abnormal oxidative stress may be pathogenic factors.

The aim of this study was determine whether intracavernosal injection (ICI) of insulin-like growth factor-1 (IGF-1) protein can improve corpus cavernosal smooth muscle relaxation in aging rats.Ten young (4-month-old) and 30 old (24-month-old) Sprague-Dawley male rats were enrolled in the study. The old rats were divided into three groups: vehicle-only (n = 10), IGF-1 1 µg/kg (n = 10) and IGF-1 10 µg/kg treatment groups (n = 10). After 4 weeks of single IGF-1 injection treatment, strips of corporal tissue were precontracted with phenylephrine, and dose-response curves were generated to evaluate endothelial-dependent [acetylcholine (ACh)], endothelial-independent [sodium nitroprusside (SNP)] and electrical field stimulation (EFS) vasoreactivity. The changes in percentage of cavernosal smooth muscle and the concentration of nitric oxide (NO) in penile tissue were also evaluated.After IGF-1 treatment, the vasoreactivity was significantly improved in both the 1 µg/kg and the 10 µg/kg treatment groups compared with the vehicle-only group at 4 weeks in response to ACh, SNP and EFS (all p0.05). The percentage of cavernosal smooth muscle was increased in the IGF-1 treatment groups. The NO concentrations were increased after IGF-1 treatment.These data demonstrate that ICI of IGF-1 can improve vasoreactivity via endothelium-dependent and endothelial-independent mechanisms in the corpus cavernosum of the aging rat.

OBJECTIVE: To compare the safety, efficacy and complications of laparoscopic pyelolithotomy (LPL) and percutaneous nephrolithotomy (PCNL) for treatment of renal pelvic stones larger than 2.5 cm. METHODS: From 2011 to 2016, 32 patients underwent LPL and another 32 patients received PCNL for renal pelvic stones larger than 2.5 cm. The baseline characteristics of the patients, stone size, mean operative time, estimated blood loss, postoperative hospital stay, stone-free rate, postoperative analgesia, blood transfusion, and the intraoperative, early postoperative and long-term complications were compared between the two groups. RESULTS: The baseline characteristics and stone size were comparable between the two groups. The mean operative time of LPL and PCNL was 117 ± 23.12 and 118.16 ± 25.45 min, respectively (P＞0.01). The two groups showed significant differences in the mean estimated blood loss (63±11.25 vs 122±27.78 mL, P＜0.01) and blood transfusion rate (0 vs 6.2%, P＜0.01) but not in postoperative hospital stay (4.5±1.34 vs 4.8±2.2 days, P＞0.01), stone-free rate (93.1% vs 87.5%, P＞0.01) or the postoperative analgesia time (1.7 ± 0.5 and 1.9 ± 0.6 days, P＞0.01). The incidence of intraoperative complications were significant lower in LPL group than in PCNL group (6.2% vs 25.0% , P＜0.01), but the incidences of early postoperative complications (25.0% vs 34.4%, P＞0.01) and long-term postoperative complications (9.4% vs 12.5%, P＞0.01) were similar between them. CONCLUSION: PCNL is the standard treatment for pelvic stones larger than 2.5 cm, but for urologists experienced with laparoscopic technique, LPL provides a feasible and safe option for management of such cases.

To investigate the risk factors of the serious complications related with double-J ureteral stent placement following percutaneous nephrolithotomy (PCNL).Clinical data were reviewed for 272 patients treated with PCNL and indwelling double-J stents between January, 2014 and April, 2016. The risk factors of serious complications were identified using univariate and multivariate logistic regression analysis.Serious complications of double-J ureteral stenting occurred in 63 patients (23.1%). Univariate and multivariate logistic regression analysis indicated that the ureter abnormalities (β=1.735, P=0.000, OR=5.670), stent indwelling duration (β=1.206, P=0.028, OR=3.340), gender (β=0.895, P=0.016, OR=2.446), preoperative urinary tract infection (β=0.849, P=0.020 , OR=2.338) and stent size (β=0.847, P=0.011, OR=2.333) were all risk factors of serious complications related with the procedure.Male patients are exposed to a higher risk of serious complications following PCNL. Effective management of urinary tract infection and choice of appropriate stent size in cases of ureteral abnormalities help to reduce these complications. The double-J stent should be withdrawn as soon as possible in patients with good postoperative recovery.

Objective To investigate the relationship between ED and CVD. Methods A total of 103 male patients aged 40–70 years old (mean age 58.3 years) with ED in Southern China were recruited. ED was assessed by International Index of Erectile Function 5 (IIEF-5) score. The presences of risk factors for CVD were evaluated by lifestyle questionnaires in those men. Results CVD increased according to severity of ED, adjusted for age, smoking, total cholesterol level, hypertension, and body mass index (P

Objective To describe the aetiology and efficacy of the treatment of persistent and recurrent hemospermia as a novel technique of transurethral seminal vesiculoscopy. Methods The clinical data of 290 patients with persistent and recurrent hemospermia (a course of hemospermia persisting more than 6 months) from multiple medical center of South China were analyzed retrospectively. The age ranged from 16 to 69 years (mean 31 years). The definite etiologies of persistent and recurrent hemospermia were confirmed by physical examination including digital rectal examination (DRE), tailored investigations such as blood PSA and clotting time, transrectal ultrasound (TRUS), CT or MRI. Of those with persistent and recurrent hemospermia, 269 patients were successfully performed by transurethral seminal vesiculoscopy since July 2008. The aetiology of the other 21 cases with persistent hemospermia were attributable to cystadenoma of the seminal vesicle [1], tuberculosis of tractus genitalis [1], bleeding risk secondary to liver cirrhosis [3], benign prostatic hyperplasia [12] and prostate cancer [4] confirmed by urogenital instrumentation or prostate biopsy. Results All the patients with persistent and recurrent hemospermia were confirmed by transurethral seminal vesiculoscopy (162 seminal vesiculitis and 108 seminal stone secondary to them, 91 ejaculatory ducts obstruction incompletely, 42 Mullerian cyst, 16 cysts of seminal vesicle, 3 cysts of ejaculatory duct and 12 benign prostatic hyperplasia). The mean operative time was 21 min (range, 5–90 min). There were no complications including injury of urethra and seminal vesicle and postoperative discomforts in the perineal region. The mean follow-up period was 24 months (range, 3–72 months). In those 269 cases, 11 patients were out of follow-up. Hematospermia in 235 cases disappeared and 23 patients respectively recurred in 5 to 60 months after receiving transurethral seminal vesiculoscopy. Of those 23 cases with postoperatively recurrent hemospermia, 12 patients were cured by re-transurethral seminal vesiculoscopy. Conclusions The aetiologies of persistent and recurrent hemospermia are mostly associated with seminal vesiculitis and seminal stone secondary to vesiculitis or ejaculatory ducts obstruction incompletely. Transurethral seminal vesiculoscopy could be an effective diagnostic and therapeutic procedure for it.

BACKGROUND FOXP3+ regulatory T cells (Tregs) inhibit effector T cell functions and are implicated in tumour progression. However, together with microvessel density (MVD) they remain controversial prognostic predictors for renal cell carcinoma (RCC), and potential associations have yet to be determined. The objective of this study was to determine the prognostic significance of Tregs and MVD and their potential relationship in RCCs. DESIGN Paraffin-embedded tissues from 62 RCC patients were analysed using immunohistochemistry to detect FOXP3+ lymphocytes, and double immunohistochemistry to detect different microvessel types in the tumour interior, rim and normal kidney tissue, and their correlation with clinicopathological characteristics. Survival analysis was also performed. RESULTS The presence of FOXP3+ cells in the tumour interior or the rim showed no correlation with death from RCC and other pathological characteristics. Negative correlations were noted between the immature MVD in the tumour interior or the rim and tumour size, tumour stage and overall survival; however, there was no correlation with the nuclear grade or pathological type. A positive correlation between FOXP3+ Tregs and immature MVD (r=0.363, P=0.014) and mature MVD (r=0.383, P=0.009) was confirmed in the tumour interior. However, there was no correlation between FOXP3+ Tregs and mature MVD (r=0.281, P=0.076) or immature MVD (r=0.064, P=0.692) in the tumour rim. CONCLUSIONS In this study, a positive correlation between the presence of FOXP3+ Tregs and immature and mature MVD in RCC was confirmed, which suggests a link between suppression of immunity, tumour angiogenesis and poor prognosis.

OBJECTIVES To compare the clinical value of single B-mode ultrasonography and B-mode combined with color Doppler ultrasonography in the guidance of mini-invasive percutaneous nephrolithotomy (m-PCNL) to decrease the incidence of hemorrhagic complications. METHODS A total of 297 patients with renal stones who had undergone m-PCNL were retrospectively categorized into 2 groups. Group 1 (187 patients) underwent m-PCNL with single B-mode ultrasound guidance and group 2 (110 patients) underwent m-PCNL with combined B-mode and color Doppler ultrasound guidance. The clinical characteristics of the patients, intraoperative and postoperative characteristics, complications, especially hemorrhagic complications, and blood transfusion rate were recorded and compared. RESULTS No statistically significant differences in age, height, weight, stone burden, operative time, stone-free rate, or length of postoperative hospital stay were found between the 2 groups. In group 2, a statistically significant decrease in the transfusion rate was found compared with group 1 (P

Incontinence after radical retropubic prostatectomy (RRP) is one of the greatest worries for all patients. One of the possible reasons for this urinary incontinence is a postoperative deficiency of the external striated urethral sphincter (EUS) complex and continence nerves. This study evaluated the application of a modified simple technique to dissection of the apical prostate in laparoscopic radical prostatectomy (LRP) and assessed the rate of urinary continence.A total of 104 patients were randomly selected using envelopes and enrolled in this study. A standard LRP was performed in 52 patients (standard LRP group) and a modified technique for simple dissection of the apical prostate in LRP was performed in another 52 patients (modified LRP group). The urethra was dissected and transected at the apex of the prostate, proximal to the nerve-distributing rhabdosphincter using sharp scissors to avoid damage to the EUS complex and continence nerves. In all patients, a pad test was performed on 3, 30 and 90 days postoperatively and correlated with urinary continence. Continence was defined as zero pads or a liner used for security reasons only.After catheter removal, the continence rates were regained in 66, 85 and 96% of patients in the modified LRP group compared with 28, 55 and 91% of the patients in the standard LRP group at 3, 30 and 90 days, respectively. A statistically significant difference was present at 3 and 30 days (p0.01, respectively). At 90 days, the difference, although still present, was not statistically significant (p0.05).In this preliminary study, the technique of simplified apical dissection of the prostate in LRP appears to be an easy and feasible technique in early recovery of urinary continence. Further long-term and larger sample studies are necessary to elucidate the modified technique in LRP on early restoration of urinary continence.

In this study we evaluate the oncological and functional results of the largest cohort of patients in China treated by laparoscopic radical prostatectomy (LRP) and with at least 3 years of follow-up. 126 inconsecutive patients (range 56–78 years, median 62.5) who had an LRP were retrospectively analyzed. The mean prostate specific antigen level and Gleason score was 13.4 ng mL−1 and 6.4, respectively. Twenty-seven patients had unilateral or bilateral nerve preservation and 29 had pelvic lymphadenectomy. Multivariate analysis was used to adjust for differences in clinical and pathological features when comparing the risk for biochemical progression-free survival (bPFS). Urinary continence was assessed by incontinence questionnaire and erectile function by the Sexual Health Inventory for Men score. The mean operative duration was 250 min and blood loss 354 mL. Five patients received blood transfusion and nine had complications, including rectal injury (two), ureteral injury (one), active bleeding (one), bladder neck stenosis (two), paralytic ileus (one), subcutaneous hematoma (one) and port-site hernia (one). The overall positive surgical margin rate was 20.6% and correlated with pathological stage and Gleason score respectively (P = 0.03, P < 0.001 respectively). All patients had ≥ 3 years of follow-up (range 3–6.75 years, mean 4.6, median 4.75). At 3 years of follow-up, the overall survival rate was 100% and the bPFS was 81.0% in all patients; 124 patients (98.4%) were continent; 22 of 27 patients (81.5%) who underwent nerve preservation retained erectile function. Our series confirms that LRP is an effective, safe and precise technique at Chinese institution.

To evaluate the value of combined use of survivin, cytokeratin (CK) 20 and mucin (MUC) 7 mRNA in comparison with voided urine cytology in the detection of bladder cancer patients. One hundred and fifty three patients and 20 healthy volunteers were evaluated by RT-PCR for detecting survivin, CK-20 and MUC7 mRNA in voided urine before cystoscopy. The three markers and cytology were evaluated independently or in combinations. The overall sensitivity and specificity were 90.4 and 94.7% for survivin, 82.6 and 97.4% for CK-20, 62.6 and 94.7% for MUC7 and 46.0 and 100% for voided urine cytology. Combined sensitivity of voided urine cytology with the three biomarkers together was higher than either combined sensitivity of voided urine cytology with one of the biomarkers or than that of the biomarker alone. Combined use of the three markers can improve the sensitivity for detecting bladder cancer.

Objective To evaluate damage to the extracorticospinal tract in Wilson disease (WD) patients using diffusion tensor imaging (DTI). Methods 70 patients with WD, including 50 with cerebral type and 20 with hepatic type, and 20 age-matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. Patients with cerebral type WD were divided into four subgroups: those with (1) hypokinesia, (2) parkinsonism, (3) mouth and throat dystonia, and (4) psychiatric symptoms. All study subjects underwent DTI of the brain. Five regions of interest (ROIs) were chosen. Fractional anisotropy (FA) and fiber volumes between ROIs were determined, and the relationships between DTI metrics and clinical status were evaluated. Results FA values and fiber volumes between subcortical nuclei were lower in WD patients. Fiber volumes between the putamen (PU) and the globus pallidus (GP), substantia nigra (SN), and thalamus (TH); between the head of the caudate nucleus (CA) and the GP and TH; and between the TH and cerebellum were lower in group 1 than in the other groups of WD patients. Fiber volumes between the GP and the SN and TH were lower in group 2, and fiber volumes between the SN and TH were lower in group 3. DTI metrics differed between patients with the cerebral and hepatic types of WD. Conclusions DTI can reconstruct the network of the extracorticospinal tract. Fiber projection between subcortical nuclei was abnormal in WD patients. Damage to fiber connections may correlate with neurological symptoms in WD patients.

Aims: The aim of this study was to evaluate the feasibility of characterizing the brain-mineral deposition in patients with Wilson disease (WD) using susceptibility-weighted imaging (SWI). Materials and Methods: The study enrolled 30 WD patients and 20 age-matched healthy controls. Neurological symptoms were scored using the modified Young Scale. The hepatic function indices, serum and urinary copper content, and serum iron content were determined. All study objects received the magnetic resonance imaging (MRI) and SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. The relationship between CP values and the clinical status were evaluated. Results: The serum iron content of WD patients was higher than the normal. The CP values of substantia nigra, caudate nucleus, and globus pallidus of WD were lower than the normal values, while the CP value of substantia nigra was the lowest. No correlations were determined between the CP values and the iron and copper parameters. There was negative correlation between the scores of dysarthria and the CP values of the globus pallidus. There was negative correlation between the scores of tremor and the CP values of caudate nucleus. Some regions, which had high signals on T2-weighted image, had low signals on SWI. Conclusions: There might be abnormal iron metabolism in patients with WD. The decreased CP values might reflect a deposition of both copper and iron. SWI may be more sensitive than the ordinary MRI. The mineral deposition may contribute to the neural symptoms.

To evaluate the impacts of three different surgical approaches to urethral stricture on the erectile function of the patients.This study included 126 male patients with urethral stricture, 35 treated by substitution urethroplasty (group A), 52 by anastomotic urethroplasty (group B), and 39 by internal urethroplasty (group C). We evaluated the pre- and postoperative erectile function of the patients using IIEF-5 scores by telephone calls and interviews. We also monitored their nocturnal penile tumescence (NPT).The IIEF-5 scores in groups A, B and C were 13.5 +/- 4.5, 11.1 +/- 4.8 and 14.5 +/- 4.41 respectively after surgery, all significantly decreased as compared with 17.1 +/- 2.6, 17.1 +/- 3.0 and 17.6 +/- 2.2 preoperatively (P0.05).All the three surgical approaches can reduce IIEF-5 scores in patients with urethral stricture, but anastomotic urethroplasty may induce a higher incidence of erectile dysfunction than the other two approaches.

To observe the secretion of insulin-like growth factor-1 (IGF-1) in corpus cavernosum smooth muscle cells (CCSMCs) in rats of different ages and explore the possible relationship of IGF-1 with aging-related erectile dysfunction (ED).We primarily cultured CCSMCs of rats aged 4, 12 and 24 months, and identified them by immunohistochemistry. We quantitatively cultured the CCSMCs in 6-well culture plates, determined the levels of IGF-1 secreted from the CCSMCs by enzyme immunoassay (EIA) and analyzed the effect of age on the IGF-1 level.CCSMCs were successfully cultured in vitro. The level of IGF-1 secreted from the CCSMCs was decreased with the increase of age, with 7.1 ng/10(5) cells in the 4-month-old group, 2.2 ng/10(5) cells in the 12-month group, and 1.9 ng/10(5) cells in the 24-month group, with statistically significant differences among the three groups (P0.01).The secretion of IGF-1 is reduced with the increase of age, and the decreased expression of IGF-1 might be associated with aging-related ED.

It remains a challenge to inhibit the local recurrence or distant metastasis of localized or locally advanced renal cell carcinoma (RCC) after surgical resection. We investigated the feasibility, safety and efficacy of immunotherapy using autologous tumor lysate (TL)-pulsed dendritic cells (DCs) and cytokine-induced killer (CIK) cells in patients with localized or locally advanced RCC.From January 2001 to July 2009, we collected 137 patients that met the selection criteria and randomly divided them into three groups. After surgery, immunotherapy with TL-pulsed DCs-CIK cells (DC-CIK group) and interferon (IFN)-α (IFN-α group) was performed in 46 patients, respectively. The other 45 patients received no postoperative adjuvant therapy (the control group). The changes in the numbers of T lymphocyte subsets, including CD4(+)CD25(high) regulatory T cells (Treg), were determined before the operation and after immunotherapy. The overall survival was compared among the three groups.An increase of the CD4(+)/CD8(+) ratio and a decrease of CD4(+)CD25(high) cells were observed after TL-pulsed DC-CIK cells or IFN-a immunotherapy. All patients tolerated the TL-pulsed DC-CIK cells immunotherapy very well, and side effects in the DC-CIK group were less than in the IFN-α group. The metastasis and recurrence rates were significantly decreased after TL-pulsed DC-CIK cells or IFN-α immunotherapy compared with the control group (P0.01). The Log-rank test showed that the overall survival rates were significantly higher in the DC-CIK group and IFN-α group than that in the control group (P0.01), but there was no difference between the DC-CIK group and IFN-α group (P0.05).Postoperative immunotherapy with TL-pulsed DC-CIK cells may prevent recurrence/metastasis and increase the overall survival rate after surgery in localized or locally advanced RCC.

To explore the effects of gene transfer of insulin like growth factor-1 (IGF-1) on the penis of senile rats and the altered levels of mRNA and protein of endothelial nitric oxide synthase (eNOS).Ten young (4 months) and 20 senile (24 months) Sprague-Dawley male rats were selected. The senile rats were divided into 2 groups: phosphate buffer solution (PBS)-only (n = 10) and 100 µg IGF-1 plasmid treatment group (n = 10). After a 4-week injection of IGF-1, the responses of intracavernous pressure (ICP) with electrical stimulation to the cavernous nerve and systemic mean arterial pressure (MAP) were evaluated. In the control and transfected senile rats, the levels of eNOS mRNA and protein were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively.The ICP/MAP and total ICP were significantly higher in the young control group versus the PBS-only group at Week 4 (P0.05). The ICP/MAP and total ICP were significantly higher in the young control group and the 100 µg IGF-1 treatment group versus the PBS-only group at Week 4 (P0.05). The levels of mRNA and protein of eNOS were higher in the 100 µg IGF-1 treatment group versus the PBS-only group at Week 4 (0.62 ± 0.16 vs 0.25 ± 0.08, 0.71 ± 0.19 vs 0.27 ± 0.09, both P0.05, respectively).The gene therapy of IGF-1 can ameliorate erectile functions and improve the levels of mRNA and protein of eNOS in senile rats.

Growth factors have a universal bioactivity. Gene therapy is a new strategy in dealing with erectile dysfunction (ED). This paper presents an overview on the value of growth factors, particularly the vascular epithelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1), in the treatment of ED.

Previous studies have confirmed the gene transfer of insulin-like growth factor-1 (IGF-1) and the IGF-1 protein can improve the erectile function in aging rats. IGF binding protein (BP)-3 can regulates the availability of IGF-I. The higher expression of IGFBP-3 may play an important role in erectile dysfunction (ED).The study aimed to investigate the mRNA and protein expression of IGFBP-3 in young and old rat penile tissues and assess the alteration of the penile structure and the NO-guanosine 3',5'-cyclic-monophosphate (cGMP) signaling pathways-related marker in ED associated with aging.The main outcome measures for this study were the expression of IGFBP-3, morphological changes, NO-cGMP signaling pathways-related marker, erectile responses were determined.Traditional reverse transcriptase polymerase chain reaction (RT-PCR) and real-time PCR were performed to examine the mRNA expression of the IGFBP-3. The Western blot was used to confirm the protein expression. Immunohistochemistry was also performed to identify the cellular localization of the encoded protein. The percentage of smooth muscle in corpus cavernosum tissue, the activity of nitric oxide synthase (NOS), and concentration of cGMP in penile tissue were also analyzed.The expression levels of IGFBP-3 of mRNA and protein were greatly increased in aging rats compared with young control rats, which is confirmed by traditional RT-PCR, real-time PCR, and Western blot (P0.01, respectively). Increased IGFBP-3 protein was localized to the epithelium of the urethra, penile endothelium, and smooth muscle in the corpus cavernosum. Significant depletion of the smooth muscle density relative to the connective tissue was also observed in the penis of the aged rats, and the lower activity of NOS and lower concentration of cGMP was also demonstrated accompanied with a significant reduction in the intracavernous pressure.Our data suggest that the increased mRNA and protein expression of IGFBP-3 in old rats may play a role in ED.

A modified apical dissection of the prostate to improve the efficiency of vesico-urethral anastomosis (VUA) in laparoscopic radical prostatectomy (LRP) was reported. A total of 42 patients were randomly selected and enrolled in this study. A standard LRP was performed in 21 patients (group 1), whereas a novel, modified apical dissection of the prostate in LRP was performed in another 21 patients (group 2). Surgical data, total operative time, VUA time, extravasation rate, catheterisation time, occurrence of anastomotic strictures, and the early and late continence rates were analysed statistically. No differences in clinical or pathological characteristics were determined between the two groups. The total operative time, VUA time, blood loss and catheterisation time were lower in group 2, which received the novel, modified technique compared with group 1, which received the standard technique to dissect the apex of the prostate (P0.05 for each). After catheter removal, a statistically significant difference in the continence rates was present at 3 and 30 days post operation in the two groups (P0.05). The novel, modified apical dissection of the prostate facilitates the VUA and significantly improves the efficacy of the procedure and early restoration of continence.

The incidence of erectile dysfunction (ED) rises with the increase of age, for which gene therapy is a new option in the recent years. Different target genes, vehicles and therapeutic strategies have been tried and yielded good results. This paper offers an overview of the current advances in gene therapy for aging-related ED.

To investigate the expression of transient receptor potential melastatin (TRPM) and transient receptor potential vanilloid (TRPV) channel family genes in rat spermatogenic cells.Rat spermatogenic cells were isolated by a mechanical procedure and the total RNA was extracted using TRIzol reagent. TRPM and TRPV channel family genes were amplified by RT-PCR and the presence of the target genes was detected by agarose gel electrophoresis. The relative gene expression levels were measured by real-time quantitative RT-PCR.TRPV5, TRPM3, TRPM4 and TRPM7 mRNAs were expressed in rat spermatogenic cells, but TRPV1, TRPV2, TRPV3, TRPV4, TRPV6, TRPM1, TRPM2, TRPM5, TRPM6, TRPM7 and TRPM8 mRNAs were not detected. The relative expressions of TRPM and TRPV mRNA were determined by quantitative real-time RT-PCR. TRPM7 expression was the highest among all the TRPM subtypes in rat spermatogenic cells, at a level equivalent to (0.0430-/+0.0034)% of beta-actin expression. TRPM3 and TRPM4 were also highly expressed, but their expression levels were only approximately 56% and 63% of that of TRPM7, respectively. For the TRPV subfamily, only TRPV5 mRNA was abundantly expressed at the level of (0.0157-/+0.0029)% relative to that of beta-actin.TRPV5, TRPM3, TRPM4 and TRPM7 mRNAs were coexpressed in spermatogenic cells in rats, among which TRPM4 and TRPM7 mRNA were expressed at high levels. TRPM4 and TRPM7 channels may be involved in the regulation of growth, differentiation and maturation of rat spermatogenic cells and are associated with the generation of the sperms.

To investigate the best dose and the long-term effect of the human insulin-like growth factor-1 (hIGF-1) gene injection into the penis of aged rats.Included in this study were 10 young (4 months old) and 40 aged (24 months old) Sprague-Dawley male rats, the latter equally divided into a PBS control and a 10 microg, a 100 microg and a 1 000 microg hIGF-1 injection group. Electrical stimulation was conducted 4 and 8 weeks after hIGF-1 injection into the penile corpus cavernous of the rats to detect the intracavernous pressure (ICP) and mean arterial pressure (MAP). Dose - and time -associated therapeutic results were analyzed and the mRNA expression of hIGF-1 determined by RT - PCR.ICP, MAP and total ICP were significant decreased by electrical stimulation in the aged rats as compared with the young ones (P0.05), statistically increased in the three hIGF-1 dose groups in comparison with the PBS controls (P0.05), and showed no obvious difference between the young rats and the latter two dose groups at 4 and 8 weeks. Although less obvious effect was achieved in the 10 microg group than in the young rats, the therapeutic result was still of significance. The mRNA expression of the hIGF-1 gene was confirmed in all the hIGF-1 treated rats.The hIGF-1 therapy can improve erectile function in aged rats, 100 microg suffices for effective erection and the effect may last at least 8 weeks for a single dose.

Bladder cancer is the most common malignancy of all genitourinary tumors. Urine cytology is the "gold standard" for non-invasive diagnosis of bladder cancer, but its sensitivity is low. This study was to explore the clinical value of combined detection with urinary bladder cancer antigen (UBC), hyaluronic acid (HA) and cytokeratin 20 (CK20) in the diagnosis of bladder cancer.Urine samples were obtained from 64 patients with bladder cancer and 20 patients with benign urological disease. Urine UBC, HA and CD20 were measured using enzyme-linked immunosorbent assay (ELISA), radioimmunology assay, and reverse transcription polymerase chain reaction (RT-PCR) respectively, before cystoscopy.UBC, HA and CK20 yielded significantly higher sensitivity in detecting bladder cancer compared to urinary cytology (85.9%, 89.1% and 78.1% vs. 40.6%, P0.01). The specificity of UBC, HA, CK20 and urinary cytology for the detection of bladder cancer were 85.0%, 80.0%, 80.0% and 95.0%, respectively. The sensitivity of UBC, HA and CK20 were all significantly higher than that of urinary cytology in detecting different histological stages and grades of bladder cancer (P0.01). The value of UBC had no significant difference in different histological stages and grades of bladder cancer (P0.05). The sensitivity of HA was significantly higher in G2 and G3 grades than in G1 grade (P0.01), but not different between G2 and G3 grades(P0.05). No difference in HA values was observed between different histological types (P0.05) regarding to HA. The sensitivity of CK20 was significantly elevated with the increase of histological grades and stages. Combined use of UBC, HA and CK20 improved the sensitivity and specificity of detecting bladder cancer to 96.9% (62/64) and 100.0%, respectively.Combined use of UBC, HA and CK20 can improve the sensitivity and specificity for the detection of bladder cancer in urine, thus it may replace conventional cystoscopy in the primary diagnosis.

Introduction Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. We have confirmed that gene transfer of IGF-1 to the penis could improve erectile capacity. However, there are some limitations in gene therapies, such as toxicity or a risk of insertional mutagenesis. Protein treatment may be another choice for decreasing these risks. Aim To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat. Main Outcome Measures Erectile responses, morphological changes, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathways-related marker were determined. Methods Ten young (4 months) and 30 old (24 months) Sprague-Dawley male rats were enrolled in this study. The old rats were divided into three groups: vehicle-only (N = 10), IGF-1 1 µg/kg (N = 10) and IGF-1 10 µg/kg treatment group (N = 10). After 4 and 8 weeks of single IGF-1 injection treatment, intracavernous pressure (ICP) responses with electrical stimulation to the cavernous nerve were evaluated. The percent of smooth muscle in corpus cavernosum tissue, the expression of mRNA and protein of endothelial nitric oxide synthase (eNOS) were also evaluated. The activity of nitric oxide synthase (NOS) and concentration of guanosine 3′,5′-cyclic-monophosphate (cGMP) that act upon the major NO-cGMP signaling pathways in penile tissue were also analyzed. Results After IGF-1 treatment, the ICP responses was significantly increased as the young control group in both the IGF-1 1 µg/kg and the IGF-1 10 µg/kg group compared with the vehicle-only group at 4 and 8 weeks ( P Conclusions IGF-1 improved erectile function in aged rats via restoration the integrity of smooth muscle of corpus cavernosum and modulation of NO-cGMP pathways. Pu, X-Y, Wang X-H, Gao W-C, Yang Z-H, and Li S-L. Insulin-like growth factor-1 restores erectile function in aged rats: Modulation the integrity of smooth muscle and nitric oxide-cyclic guanosine monophosphate signaling activity.

To evaluate the long-term efficacy and safety of transurethral resection of bladder tumor (TURBT) with bipolar plasmakinetic energy.We reviewed the records of 121 patients with superficial transitional cell carcinoma of the bladder treated at our institute. Bipolar TURBT with plasmakinetic energy was performed for diagnostic and therapeutic purposes in all patients. Resected tissue was examined by a pathologist who recorded the number of tumors, tumor size, tumor shape, location, grade, invasion of the muscularis propria, and presence of muscular invasion. The operating time, length of hospital stay, blood loss, and intraoperative and postoperative complications were recorded by a urologist. Follow-up was 3 to 5.5 years after operation.The median age of the patients was 61 years; 41 patients had multiple tumors and 80 had single tumors. The mean tumor size was 1.9 cm in diameter. The tumor was located in the lateral wall of the bladder in 67 patients. The mean operative time was (25 +/- 16) minutes and the mean postoperative hospitalization period was 3 days. Three (2.5%) patients had hematuria requiring blood transfusion and 2 (1.7%) patients had bladder perforation. Adductor contraction was noted in 6 patients (4.9%), and urethral strictures occurred in 5 patients (4.1%).Transurethral resection of bladder tumors with bipolar plasmakinetic energy is safe and effective in the treatment of superficial bladder tumors.

To report our operative technique and initial outcomes of laparoscopic radical cystectomy (LRC) and external orthoptic gastric neobladder. Since 2003, nine patients have undergone laparoscopic radical cystectomy with orthotopic gastric neobaldder at our institution. The specimen is extracted through a 6-cm vertical minilaparotomy incision above the umbilicus. The gastric neobladder was constructed as our open technique using the part of stomach body and antrum with the pedicle of gastroepiploic vascular bundle through the site of specimen retrieval. The operative data, complications and follow-up functional data were analyzed. The mean operative time was 365 min (300–450). Mean blood loss was 520 ml (200–1,500) and four patients (44.4%) required blood transfusion. In all cases no conversion to open surgery was necessary. The length of stay was 17 days and the total complication rate was 55.6% (five cases). All patients were free of recurrence at a mean follow-up of 22 months (3–48). The day and night incontinence rate was 11.1 and 44.4%, respectively. At 6 months after operation, urodynamic evaluations indicated a larger capacity, low pressure urinary reservoir. Laparoscopic radical cystectomy with orthotopic gastric neobladder is a feasible intervention. The external construction of the gastric neobladder using the part of stomach body and antrum is quick and safe. With precise and increased operative technique, the LRC with orthotopic gastric baldder may be a good choice for urinary diversion. However, the larger samples, long-term compared studies with bowel diversions are required to evaluate this new technique.

Aim: To investigate the expression and distribution of the members of the transient receptor potential (TRP) channel members of TRP melastatin (TRPM) and TRP vanilloid (TRPV) subfamilies in rat prostatic tissue. Methods: Prostate tissue was obtained from male Sprague-Dawley rats. Reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time polymerase chain reaction (PCR) were used to check the expression of all TRPM and TRPV channel members with specific primers. Immunohistochemistry staining for TRPM8 and TRPV1 were also performed in rat tissues. Results: TRPM2, TRPM3, TRPM4, TRPM6, TRPM7, TRPM8, TRPV2 and TRPV4 mRNA were detected in all rat prostatic tissues. Very weak signals for TRPM1, TRPV1 and TRPV3 were also detected. The mRNA of TRPM5, TRPV5 and TRPV6 were not detected in all RT-PCR experiments. Quantitative real-time RT-PCR showed that TRPM2, TRPM3, TRPM4, TRPM8, TRPV2 and TRPV4 were the most abundantly expressed TRPM and TRPV subtypes, respectively. Fluorescence immunohistochemistry indicated that TRPM8 and TRPV1 are highly expressed in both epithelial and smooth muscle cells. Conclusion: Our results demonstrate that mRNA or protein for TRPM1, TRPM2, TRPM3, TRPM4, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV3 and TRPV4 exist in rat prostatic tissue. The data presented here assists in elucidating the physiological function of TRPM and TRPV channels.

To comparatively evaluate the effect of 3- versus 8-month neoadjuvant hormonal therapy (NHT) on laparoscopic radical prostatectomy (LRP) operative and postoperative parameters.We evaluated 55 patients with clinically localized prostate cancer treated by 3-month (25 patients, group-1), 8-month NHT (19 patients, group-2) and non-neoadjuvant therapy (11 patients, group-3) before LRP. Serum PSA levels and prostate volume were measured and evaluated monthly before operation. The operative and postoperative parameters were recorded and compared in the three different groups.Transrectal ultrasound determined that prostate volume decreased 39.6% in group 1 and 35.4% in group 2 after 3-month NHT and a further 34.4% in group 2 after 8-month NHT. The mean prostate volume was significantly smaller after 8-month than 3-month NHT in group 2 (P0.05). Mean serum PSA decreased 97.8% in group 1 and 98.1% in group 2 after 3-month NHT. A further 72.9% PSA decrease was determined after 8-month NHT in group 2. There were no significant differences in the three groups with respect to mean operative time, mean blood loss, transfusion rate, operative difficulty, catheterization time, hospital time and complication rate (P0.05, respectively). Positive margin rate was significantly lower in the 3- or 8-month NHT group than in the non-adjuvant group (P0.05, respectively). However, there was no significant difference between the 3- and 8-month groups with respect to positive margin rate (P0.05).The prolonged NHT (8-month) did not affect the operative or postoperative parameters. The LRP can be safely performed in patients after prolonged NHT. Prospective randomized studies are required to determine whether prolonged NHT reduces the risk of biochemical recurrence after LRP.

To determine the incidence of erectile dysfunction (ED) after PlasmaKinetic vaporization of the prostate (PKVP) using objective and subjective parameters and risk factors.A total of 153 men completed a questionnaire detailing perceived sexual dysfunction and underwent nocturnal penile-tumescence testing using the RigiScan for three consecutive nights 3 or 4 days preoperatively and 3 months postoperatively. The International Index of Erectile Function (IIEF)-5 scores were obtained preoperatively and postoperatively. Full details of each operation were recorded, including grams of tissue resected, operative time, any short-term complications, especially emphasizing capsular perforation, and concomitant diseases such as diabetes and hypertension. The association of risk factors with the development of ED after PKVP was assessed. Complete data were available for 103 men (67.3%). Their mean age was 62.1 years (range 48-83 years).Postoperatively, 11 patients (10.6%) were found to have ED. Patients who developed ED postoperatively had a lower IIEF-5 score and penile-tumescence parameters preoperatively (for all parameters, P0.0001). As risk factors, diabetes, capsular perforation, and an IIEF-5 score21 were found to be significant.The incidence of ED after PKVP measured objectively was 10.6%. In the absence of the risk factors, PKVP is a safe therapeutic strategy with regard to sexual function.

Aim: To determine whether adenoviral gene transfer of insulin like growth factor-1 (IGF-1) to the penis of streptozotocin (STZ)-induced diabetic rats could improve erectile capacity. Methods: The STZ diabetic rats were transfected with AdCMV-βgal or AdCMV-IGF-1. These rats underwent cavernous nerve stimulation to assess erectile function and their responses were compared with those of age-matched control rats 1 to 2 days after transfection. In control and transfected STZ diabetic rats, IGF-1 expression were examined by reverse transcription polymerase chain reaction (RT-PCR), Western blot and histology. The penis β-galactosidase activity and localization of the STZ diabetic rats were also determined. Results: One to two days after transfection, the β-galactosidase was found in the smooth muscle cells of the diabetic rat penis transfected with AdCMV-βgal. One to 2 days after administration of AdCMV-IGF-1, the cavernosal pressure, as determined by the ratio of maximal intracavernous pressure-to-mean arterial pressure (ICP/MAP) and total intracavernous pressure (ICP), was increased in response to cavernous nerve stimulation. Transgene expression was confirmed by RT-PCR, Western blot and histology. Conclusion: Gene transfer of IGF-1 significantly increased erectile function in the STZ diabetic rats. These results suggest that in vivo gene transfer of IGF-1 might be a new therapeutic intervention for the treatment of erectile dysfunction (ED) in the STZ diabetic rats. Edited by Prof. Aleksander Giwercman

Sildenafil is an orally effective therapy for the treatment of men with erectile dysfunction (ED). It is a specific and selective inhibitor of phosphodiesterase type 5 (PDE5). This paper reviews the researches on the pharmacokinetics, the onset and duration of the action of Sildenafil.