Reduced nitrite accumulation at the primary nitrite maximum in the cyclonic eddies in the western North Pacific subtropical gyre.

Nitrite, an intermediate product of the oxidation of ammonia to nitrate (nitrification), accumulates in upper oceans, forming the primary nitrite maximum (PNM). Nitrite concentrations in the PNM are relatively low in the western North Pacific subtropical gyre (wNPSG), where eddies are frequent and intense. To explain these low nitrite concentrations, we investigated nitrification in cyclonic eddies in the wNPSG. We detected relatively low half-saturation constants (i.e., high substrate affinities) for ammonia and nitrite oxidation at 150 to 200 meter water depth. Eddy-induced displacement of high-affinity nitrifiers and increased substrate supply enhanced ammonia and nitrite oxidation, depleting ambient substrate concentrations in the euphotic zone. Nitrite oxidation is more strongly enhanced by the cyclonic eddies than ammonia oxidation, reducing concentrations and accelerating the turnover of nitrite in the PNM. These findings demonstrate a spatial decoupling of the two steps of nitrification in response to mesoscale processes and provide insights into physical-ecological controls on the PNM.

A multicenter retrospective study of transurethral prostate split for benign prostate hyperplasia.

Background: Transurethral split of the prostate (TUSP) is effective in treating benign prostatic hyperplasia (BPH). However, there is still a lack of research focusing on the optimal target population for TUSP. This study aimed to compare the efficacy of TUSP in patients with different prostate volumes or ages. Methods: The study was a multicenter retrospective study. The outcomes of TUSP in BPH patients with different prostate volumes or different ages were compared. A total of 439 patients were included in the study. Patients were divided into two groups according to prostate volume, with a cut-off value of 50 mL. Similarly, the cut-off value for the age groups was 70 years. Baseline patient characteristics and perioperative outcomes were recorded. Follow-up was performed at 1, 6, and 12 months after surgery. Results: The mean age of the patients was 73.4 years, and the mean prostate volume was 51.2 mL. At 12-month follow-up after TUSP treatment, the patients' International Prostate Symptom Scores (IPSS), quality of life (QoL) scores, and postvoid residual (PVR) volumes decreased significantly, while peak urinary flow rate (Qmax) increased significantly. Intraoperative hemoglobin (Hb) reduction was significantly lower in the small volume group than in the large volume group. The incidence of postoperative urinary urgency and transient incontinence was lower in the small volume group. IPSS score, PVR, and Qmax in the small volume group showed more remarkable changes at several time points compared to the preoperative period. Postoperative pain scores were higher in the small volume group than in the large volume group. There were no differences between the two groups in terms of long-term complications. The younger group showed greater variation in PVR and Qmax at some time points but less variation in QoL than the older group. Conclusions: TUSP is overall safe and effective in treating BPH. This study showed differences in the outcomes of TUSP in treating different prostate volumes or ages of BPH patients. The optimal surgical approach for BPH patients might be selected clinically based on a combination of prostate volume or patient age.

Activity and safety of SHR3680, a novel antiandrogen, in patients with metastatic castration-resistant prostate cancer: a phase I/II trial.

BACKGROUND: Antagonizing the androgen-receptor (AR) pathway is an effective treatment strategy for patients with metastatic castration-resistant prostate cancer (CRPC). Here, we report the results of a first-in-human phase 1/2 study which assessed the safety, pharmacokinetics, and activity of SHR3680 (a novel AR antagonist) in patients with metastatic CRPC. METHODS: This phase 1/2 study enrolled patients with progressive metastatic CRPC who had not been previously treated with novel AR-targeted agents. In the phase 1 dose-escalation portion, patients received oral SHR3680 at a starting daily dose of 40 mg, which was subsequently escalated to 80 mg, 160 mg, 240 mg, 360 mg, and 480 mg per day. In phase 2 dose-expansion portion, patients were randomized to receive daily dose of 80 mg, 160 mg, or 240 mg of SHR3680. The primary endpoint in phase 1 was safety and tolerability and in phase 2 was the proportion of patients with a prostate-specific antigen (PSA) response (≥ 50% decrease of PSA level) at week 12. RESULTS: A total of 197 eligible patients were enrolled and received SHR3680 treatment, including 18 patients in phase 1 and 179 patients in phase 2. No dose-limiting toxicities were reported and the maximum tolerated dose was not reached. Treatment-related adverse events (TRAEs) occurred in 116 (58.9%) patients, with the most common one being proteinuria (13.7%). TRAEs of grade ≥ 3 occurred in only 23 (11.7%) patients, and no treatment-related deaths occurred. Antitumor activities were evident at all doses, including PSA response at week 12 in 134 (68.0%; 95% CI, 61.0-74.5) patients, stabilized bone disease at week 12 in 174 (88.3%; 95% CI, 87.2-95.5) patients, and responses in soft tissue lesions in 21 (34.4%, 95% CI, 22.7-47.7) of 61 patients. CONCLUSION: SHR3680 was well tolerated and safe, with promising anti-tumor activity across all doses tested in patients with metastatic CRPC. The dose of 240 mg daily was recommended for further phase 3 study. TRIAL REGISTRATION: Clinical trials.gov NCT02691975; registered February 25, 2016.

Nutrient regulation of biological nitrogen fixation across the tropical western North Pacific.

Nitrogen fixation is critical for the biological productivity of the ocean, but clear mechanistic controls on this process remain elusive. Here, we investigate the abundance, activity, and drivers of nitrogen-fixing diazotrophs across the tropical western North Pacific. We find a basin-scale coherence of diazotroph abundances and N2 fixation rates with the supply ratio of iron:nitrogen to the upper ocean. Across a threshold of increasing supply ratios, the abundance of nifH genes and N2 fixation rates increased, phosphate concentrations decreased, and bioassay experiments demonstrated evidence for N2 fixation switching from iron to phosphate limitation. In the northern South China Sea, supply ratios were hypothesized to fall around this critical threshold and bioassay experiments suggested colimitation by both iron and phosphate. Our results provide evidence for iron:nitrogen supply ratios being the most important factor in regulating the distribution of N2 fixation across the tropical ocean.

Comparison between a transurethral prostate split and transurethral prostate resection for benign prostatic hyperplasia treatment in a small prostate volume: a prospective controlled study.

BACKGROUND: Transurethral resection of the prostate (TURP) was considered the golden standard to treat benign prostatic hyperplasia (BPH) for decades. However, TURP was associated with low efficiency to alleviate the lower urinary tract symptoms (LUTS) and a significantly higher risk of bladder neck contracture (BNC) for patients with small-volume BPH. Our study aims to compare the therapeutic effect of a transurethral split of the prostate (TUSP) with TURP for patients with small-volume BPH (<30 mL). METHODS: In this study, 101 small-volume BPH patients were randomly divided into two groups (TUSP and TURP group). The patient's baseline characteristics and perioperative outcomes were recorded. The follow-up was done at six months, one year and two years after surgical treatment. RESULTS: No significant differences were observed between the two groups for the baseline characteristics, including age, prostate volume, prostate-specific antigen (PSA) level, concurrent disease, post-void residual (PVR), maximum urinary flow rate (Qmax), international prostate symptoms score (IPSS), and quality of life (QoL) score. The operative time and hemoglobin decrease were significantly lower in the TUSP group compared to the TURP group. However, no significant differences were observed between both groups for catheterization time, postoperative hospital stay, and incidence of transurethral resection syndrome (TURS). However, of the late complications, the incidence of BNC in the TUSP group was significantly lower than the TURP group. No significant differences were found between both groups for other complications, including postoperative bleeding, micturition urgency, micturition frequency, micturition pain, urinary tract infection, recatheterization, transient incontinence, and continuous incontinence. Follow-up results showed that the IPSS of the TUSP group was significantly lower than the TURP group, while the Qmax of the TUSP group was significantly higher than the TURP group. CONCLUSIONS: This study shows that TUSP may be an efficient and safe treatment for small-volume BPH (<30 mL) with a lower incidence of postoperative BNC and better longtime clinical outcomes than TURP. It suggested that TUSP could be an ideal treatment choice for small-volume BPH.

The diagnostic value of prostate cancer between holmium laser enucleation of the prostate and transurethral resection of the prostate for benign prostatic hyperplasia: A retrospective comparative study.

BACKGROUND: To compare the diagnostic value of prostate cancer (PCa) between holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP). METHODS: We retrospectively analyzed the clinical data of 2909 patients who underwent surgery for benign prostatic hyperplasia (BPH) from January 2008 to June 2018. A total of 1362 patients received HoLEP, and 1547 patients received TURP. The baseline patient characteristics were collected. We then compared the perioperative outcomes of these patients who diagnosed with incidentally diagnosed prostatic carcinoma (IDPC) or PCa after BPH surgeries. RESULTS: The total detection rate of PCa in HoLEP group was higher than that in TURP group (85/6.24% vs. 61/3.94%, p = 0.005). Specifically, 55(4.6%) patients were diagnosed with IDPC in HoLEP group with prostate-specific antigen (PSA) less than 4 ng/ml, and 37(2.7%) patients in TURP group (p = 0.014). For the patients with PSA between 4 and 10 ng/ml, 15(13.9%) patients were diagnosed with PCa after HoLEP, and 6(5.0%) patients after TURP (p = 0.023). But the detection rate of PCa was not significantly different between the two groups when PSA was over 10 ng/ml. On the other hand, 57 in 1215 patients with no prostate biopsy preoperatively were diagnosed with PCa after HoLEP, while 42 in 1370 patients after TURP (4.7% vs. 3.1%, p = 0.040), respectively. Twenty-six patients received once biopsy and diagnosed with PCa in HoLEP group, while 15 patients in TURP group (18.4% vs. 8.9%, p = 0.018), respectively. However, no significant difference was observed for patients who received twice prostate biopsy in the two groups. CONCLUSIONS: The present study showed that HoLEP can provide a higher total detection rate of PCa when compared with TURP. Besides, this superiority was especially embodied in patients with PSA less than 10 ng/ml.

Diagnosis of CO2 dynamics and fluxes in global coastal oceans.

Global coastal oceans as a whole represent an important carbon sink but, due to high spatial-temporal variability, a mechanistic conceptualization of the coastal carbon cycle is still under development, hindering the modelling and inclusion of coastal carbon in Earth System Models. Although temperature is considered an important control of sea surface pCO2, we show that the latitudinal distribution of global coastal surface pCO2 does not match that of temperature, and its inter-seasonal changes are substantially regulated by non-thermal factors such as water mass mixing and net primary production. These processes operate in both ocean-dominated and river-dominated margins, with carbon and nutrients sourced from the open ocean and land, respectively. These can be conceptualized by a semi-analytical framework that assesses the consumption of dissolved inorganic carbon relative to nutrients, to determine how a coastal system is a CO2 source or sink. The framework also finds utility in accounting for additional nutrients in organic forms and testing hypotheses such as using Redfield stoichiometry, and is therefore an essential step toward comprehensively understanding and modelling the role of the coastal ocean in the global carbon cycle.

Comparison of Diode Laser (980 nm) Enucleation vs Holmium Laser Enucleation of the Prostate for the Treatment of Benign Prostatic Hyperplasia: A Randomized Controlled Trial with 12-Month Follow-Up.

Objective: To compare the clinical efficacy and safety between diode laser (980 nm) enucleation of the prostate (DiLEP) and holmium laser enucleation of the prostate (HoLEP) for treating benign prostatic hyperplasia (BPH). Patients and Methods: One hundred twenty-six BPH patients in our hospital from December 2016 to December 2017 were enrolled in this study. They were randomized to the DiLEP group or HoLEP group, which were administrated with DiLEP and HoLEP treatment, respectively. The patient's characteristics, such as age, body mass index, comorbidities, prostate volume, and prostate-specific antigen, were recorded before surgery. The perioperative outcomes and complications were also compared. The maximum flow rate (Qmax), postvoid residual (PVR), international prostate symptom score (IPSS), and quality-of-life (QoL) score were assessed at baseline and 3, 6, and 12 months postoperatively. Results: No significant differences were observed for the patient's baseline characteristics between both groups. For the perioperative outcomes, including operative time, resected tissue weight, catheter duration, and hospital stay, no significant difference was found between the two groups. However, the DiLEP group showed less blood loss and decrease in hemoglobin compared with the HoLEP group. The incidence of early or late complications was similar for both groups. The Qmax, PVR, IPSS, and QoL for both groups of patients were dramatically improved after surgery. By comparing the Qmax, PVR, IPSS, and QoL between the two groups, no significant differences were detected in the 3-, 6-, or 12-month follow-up. Conclusions: This study demonstrated that both DiLEP and HoLEP are efficient and safe treatments for BPH patients. DiLEP showed less blood loss and decrease in hemoglobin than HoLEP, which indicated that the diode laser (980 nm) generates a better hemostasis effect.

Adjuvant hormone therapy after radical prostatectomy in high-risk localized and locally advanced prostate cancer: First multicenter, observational study in China.

OBJECTIVE: Potential of combined androgen blockade (CAB) has not been explored extensively in Chinese males with prostate cancer (PCa). Therefore, this study evaluated the 2-year prostate-specific antigen (PSA) recurrence rate and quality of life (QoL) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy (HT) after radical prostatectomy (RP). METHODS: This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor (preoperative PSA>20 ng/mL or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator's decision in routine clinical practice. Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate (FACT-P) QoL scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up. RESULTS: A total of 189 patients (mean age: 66.9±6.5 years) were recruited, among which 112 (59.3%) patients showed serum PSA>20 ng/mL preoperatively. The highest postoperative pathological advancement noticed was from clinical T2 (cT2) to pathological T3 (pT3) (43.9%) stage. The majority of the patients (66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence (15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist (LHRHa) (16.1%), and antiandrogen (19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P QoL score of 119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months. CONCLUSIONS: Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in high-risk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens (AA) or LHRHa therapy. Further long-term therapy (>12 months) significantly improved QoL compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving QoL.

Thymol inhibits bladder cancer cell proliferation via inducing cell cycle arrest and apoptosis.

Thymol is a phenolic compound with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-tumor effects. However, the effect of thymol on bladder cancer cell growth is still elusive. The purpose of this study is to investigate the efficacy of thymol in bladder cancer cells and its underlying mechanism. Thymol inhibited bladder cancer cell proliferation in a dose and time-dependent manner. We also observed cell cycle arrest at the G2/M phase after the treatment of thymol. Moreover, thymol could induce apoptosis in bladder cancer cells via the intrinsic pathway along with caspase-3/9 activation, release of cytochrome c and down-regulation of anti-apoptotic Bcl-2 family proteins. The activation of JNK and p38 was also critical for thymol-induced apoptosis since it was abrogated by the treatment of JNK inhibitor (SP600125), and p38 inhibitor (SB203580) but not ERK inhibitor (SCH772984). Furthermore, the generation of ROS (reactive oxygen species) was detected after the treatment of thymol. ROS scavenger NAC (N-acetyl cysteine) could block the thymol-triggered apoptosis and activation of MAPKs. These findings offer a novel therapeutic approach for bladder cancer.

Results of a randomized, double-blind, active-controlled clinical trial with propiverine extended release 30 mg in patients with overactive bladder.

OBJECTIVE: To compare the efficacy and safety of the 30 mg extended release (ER) formulation of propiverine hydrochloride with the 4 mg ER formulation of tolterodine tartrate in patients with overactive bladder (OAB) in a non-inferiority trial. PATIENTS AND METHODS: Eligible patients, aged 18-75 years and with symptoms of OAB, were enrolled in this multicentre, randomized, double-blind, parallel-group, active-controlled study. After a 2-week screening period, patients were randomized at a 1:1 ratio to receive either propiverine ER 30 mg or tolterodine ER 4 mg daily during the 8-week treatment period. Efficacy was assessed using a 3-day voiding diary and patient's self-reported assessment of treatment effect. Safety assessment included recording of adverse events, laboratory test results, measurement of post-void residual urine and electrocardiograms. RESULTS: A total of 324 patients (244 female and 80 male) were included in the study. Both active treatments improved the variables included in the voiding diary and in the patient's self-reported assessment. The change from baseline in the number of voidings per 24 h was significantly greater in the propiverine ER 30 mg group compared with the tolterodine ER 4 mg group after 8 weeks of treatment (full analysis set [FAS] -4.6 ± 4.1 vs -3.8 ± 5.1; P = 0.005). Significant improvements were also observed for the change of urgency incontinence episodes after 2 weeks (P = 0.026) and 8 weeks (P = 0.028) of treatment when comparing propiverine ER 30 mg with tolterodine ER 4 mg. Both treatments were well tolerated, with a similar frequency of adverse drug reactions in both the propiverine ER 30 mg and tolterodine ER 4 mg groups (FAS 40.7 vs 39.5%; P = 0.8). More patients treated with tolterodine ER 4 mg discontinued the treatment because of adverse drug reactions compared with propiverine ER 30 mg (7.4 vs 3.1%). CONCLUSIONS: Propiverine ER 30 mg was confirmed to be an effective and well-tolerated treatment option for patients with OAB symptoms. This first head-to-head study showed non-inferiority of propiverine ER 30 mg compared with tolterodine ER 4 mg.

Minimally invasive percutaneous nephrolithotomy versus endoscopic combined intrarenal surgery with flexible ureteroscope for partial staghorn calculi: A randomised controlled trial.

BACKGROUND: To compare the efficacy and safety of simultaneous percutaneous nephrolithotomy combined with flexible ureteroscopic lithotripsy in Galdakao-Modified Supine Valdivia position (GMSV) with minimally invasive percutaneous nephrolithotomy (MPCNL) for partial staghorn calculi. METHODS: 67 patients with partial staghorn calculi were randomly divided into two groups. In MPCNL Group, conventional MPCNL was performed in the prone position. In the other group, simultaneous combined MPCNL and flexible ureteroscopic lithotripsy (Endoscopic Combined Intra-Renal Surgery, ECIRS) serves as single session treatment in the GMSV position (ECIRS Group). Demographic, clinical characteristic, perioperative complications and stone free rate (SFR) were recorded. RESULTS: No significant difference was detected between two groups concerning the age, body mass index, hydronephrosis, stone burden and location. The mean operative time was 105.33 ± 30.28 min in ECIRS group, which is longer (p = 0.002) than MPCNL group (83.58 ± 24.37 min). The one-step SFR was significantly higher (p = 0.007) in the ECIRS group compared to MPCNL group (87.88% vs 58.82%). The mean blood loss was 77.21 ± 41.21 ml for ECIRS group and 86.43 ± 35.61 ml for MPCNL group (p = 0.330). Overall, complication rate is low in both groups. No statistical difference was found in regards to the clinical complications between the two groups (p = 0.409). After the ancillary treatments, the final SFR was 96.97% in ECIRS group and 91.18% in MPCNL group (p = 0.628). CONCLUSION: Simultaneous combined MPCNL and flexible ureteroscopic lithotripsy is an effective and safe treatment for partial staghorn calculi, with significantly higher one-step SFR when compared to conventional MPCNL monotherapy, without additional procedure-related complications.

Abiraterone acetate for metastatic castration-resistant prostate cancer after docetaxel failure: A randomized, double-blind, placebo-controlled phase 3 bridging study.

OBJECTIVES: To evaluate the efficacy and safety of abiraterone acetate-prednisone versus placebo-prednisone in Asian metastatic castration-resistant prostate cancer patients who have failed docetaxel-based chemotherapy. METHODS: In this double-blind, phase 3 study from China, 214 patients were randomized (2:1) to abiraterone acetate 1000 mg once daily plus prednisone 5 mg twice daily and placebo plus prednisone 5 mg twice daily in 28-day treatment cycles. RESULTS: Abiraterone acetate-prednisone treatment significantly decreased prostate-specific antigen progression risk by 49%, with longer median time to prostate-specific antigen progression of 5.55 months versus 2.76 months in the placebo-prednisone group (hazard ratio 0.506, P = 0.0001, primary end-point). There was a strong trend for improved overall survival in the abiraterone acetate-prednisone group, with a 40% decrease in the risk of death (hazard ratio 0.604, P = 0.0597); however, median survival was not reached in either group because of the short follow-up period (12.9 months) and limited number of observed death events. The prostate-specific antigen response rate was higher in the abiraterone-prednisone group (49.7%) than in the placebo-prednisone group (14.1%). A total of 37.1% patients in this group had pain progression events compared with 50.7% in the placebo-prednisone group. Abiraterone-prednisone significantly decreased the risk of pain progression by 50% (hazard ratio 0.496, P = 0.0014). The incidence of adverse events was similar between the two groups; the most common adverse events being anemia (25.9% for abiraterone-prednisone vs 22.5% for placebo-prednisone), hypokalemia (25.9% and 11.3%), bone pain (23.8% and 21.1%), hypertension (16.1% and 12.7%) and increased aspartate aminotransferase (14.7% and 15.5%), respectively. CONCLUSIONS: Abiraterone-prednisone significantly delays disease and pain progression, and prostate-specific antigen, with a favorable benefit-risk ratio in Asian metastatic castration-resistant prostate cancer patients in the post-docetaxel setting.

[Transurethral resection of the prostate versus transurethral holmium laser enucleation of the prostate for benign prostatic hyperplasia with bladder detrusor overactivity].

OBJECTIVE: To compare and analyze the effects of transurethral resection of the prostate (TURP) and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with bladder detrusor overactivity. METHODS: his study included 51 cases of BPH with bladder detrusor overactivity treated by TURP and another 58 treated by HoLEP. We evaluated the urination of the two groups of patients during the recovery period and at 3 and 6 months postoperatively. RESULTS: There were no statistically significant differences in such baseline data as the blood PSA level, prostate volume, International Prostate Symptom Score (IPSS), and quality of life (QOL) between the two groups of patients, except in effective bladder capacity, which was higher in the TURP than in the HoLEP group (ï¼»315±59ï¼½ vs ï¼»287±76ï¼½ ml, P<0.05). Urine storage symptoms were obviously improved in both of the groups postoperatively, with the storage symptoms score significantly decreased from 12.6±4.9 preoperatively to 7.5±3.9 at 3 months and 6.1±4.2 at 6 months after surgery in the TURP group (P<0.01) and from 13.7±5.7 to 7.9±4.2 and 7.0±5.1 in the HoLEP group (P<0.01). HoLEP manifested significant advantages over TURP in the postoperative urethral catheterization time (ï¼»2.7±0.8ï¼½ vs ï¼»5.1±1.2ï¼½ d, P<0.05), postoperative bladder contracture time (ï¼»4.1±1.9ï¼½ vs ï¼»5.8±2.4ï¼½ d, P<0.05), postoperative hospital stay (ï¼»4.4±1.8ï¼½ vs ï¼»5.9±2.5ï¼½ d, P<0.05), and improvement of the maximum urinary flow rate, which was increased from (7.9±3.7) ml/s preoperatively to (16.8±4.3) ml/s at 3 months after surgery in the HoLEP group and from (8.6±3.2) ml/s to (14.6±4.3) ml/s in the TURP group (P<0.05). CONCLUSIONS: Both TURP and HoLEP can improve bladder function and detrusor overactivity in BPH patients, with similar effects in improving urination at 3 to 6 months after surgery. However, HoLEP has more advantages over TURP during the period of postoperative recovery.

A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats.

Diabetes is an important risk factor for erectile dysfunction (ED). Recent studies have indicated that A2B adenosine receptor (ADORA2B) signaling is essential for penile erection. Thus, we hypothesize that diabetic ED may be attributed to impaired A2B adenosine signaling. To test this hypothesis, we generated diabetic rats by injecting streptozocin as animal model. After 12 weeks, immunohistochemistry staining was used to localize the expression of ADORA2B. Western Blot and quantitative PCR were employed to determine ADORA2B expression level. Intracavernosal pressure (ICP) measurement was used to evaluate erectile function. Diabetic rats received a single intravenous injection of BAY 60-6583, an ADORA2B agonist, or vehicle solution, at 60 min before the ICP measurement. The results showed that ADORA2B expressed in the nerve bundle, smooth muscle, and endothelium in penile tissue of control mice. Western Blot and quantitative PCR results indicated that the expression levels of ADORA2B protein and mRNA were significantly reduced in penile tissues of diabetic rats. Functional studies showed that the erectile response induced by electrical stimulation was remarkably decreased in diabetic rats, compared with age-matched control rats. However, at 60 min after BAY 60-6583 treatment, the erectile function was improved in diabetic rats, suggesting that enhancement of ADORA2B signaling may improve erectile function in diabetic ED. This preclinical study has revealed a previously unrecognized therapeutic possibility of BAY 60-6583 as an effective and mechanism-based drug to treat diabetic ED. In conclusion, we propose that impaired A2B adenosine signaling is one of the pathological mechanisms of diabetic ED.

The Clinical Efficacy and Safety of Ureteroscopic Laser Papillotomy to Treat Intraductal Papillary Calculi Associated With Medullary Sponge Kidney.

OBJECTIVE: To evaluate the safety, efficacy, and durability of ureteroscopic laser papillotomy for the treatment of radiographically visible intraductal papillary calculi and/or free collecting system calculi associated with medullary sponge kidney (MSK). METHODS: The medical records of 25 MSK patients who underwent ureteroscopic laser papillotomy were reviewed at our institution from 2010 to 2013. The follow-up was made in our outpatient department. Pain was assessed using a standard verbal analog pain scale. Patients' pain score, plain abdominal radiograph, ultrasound examination, and urine analysis were routinely performed for each follow-up. We evaluated the procedure-related complications and mean-estimated glomerular filtration rate. RESULTS: Ureteroscopic laser papillotomy was performed a total of 37 times in 25 patients, including 12 bilateral procedures and 13 unilateral procedures. Significantly less pain was reported after 32 procedures. The mean operative time for unilateral procedure was 38.5 ± 8.2 minutes. The main complications after surgery included urinary infection (2 patients). No serious bleeding was presented in all the patients. The maximum follow-up time was 28.5 months. There was no significant change in the mean-estimated glomerular filtration rate before and after the procedure and at the end of follow-up. Twenty-three patients remained asymptomatic, whereas 2 patients had urinary tract infection (pyelonephritis) during follow-up. CONCLUSION: In MSK patients with repeated recurrences of symptomatic stones, ureteroscopic laser papillotomy could be a safe and effective treatment option for radiographically visible intraductal papillary calculi.

A comparative study to analyze the efficacy and safety of flexible ureteroscopy combined with holmium laser lithotripsy for residual calculi after percutaneous nephrolithotripsy.

A certain proportion of patients with initial Percutaneous nephrolithotripsy (PCNL) management require ancillary procedures to increase the stone-free rate. In this study, we aim to analyze the efficacy and safety of flexible ureteroscopy combined with holmium laser lithotripsy (F-UL) for treatment of residual calculi after PCNL by comparison with extracorporeal shockwave lithotripsy (SWL). Total of 96 patients with residual renal calculi (4 mm to 20 mm) after PCNL was enrolled from May 2010 to March 2013. They were randomly divided into two groups: US Group: patients were treated with F-UL; SWL Group: patients were treated with SWL. Follow-up was made one month and three months after treatment. The mean residual stone size after PCNL was 12.4 ± 4.3 mm in US group compared with 11.9 ± 4.5 in SWL group. The stone-free rate was 84.7% one month after surgical procedure in US group, this rate increased to 91.3% in the third months, while the stone-free rate in SWL group is 64.6% one month after treatment and 72.9% in the third month. For residual stone in lower calyx, the stone-free rate three month after treatment was 90.4% in US group compared to 65.2% in SWL group (P < 0.05). The overall complication rate was low in both groups, no severe complication was found. Both F-UL and SWL are safe and effective methods for residual calculi after PCNL, without severe complications. F-UL provided significantly higher stone-free rate compared with SWL, especially for low-pole calculi.

Four-arm robotic partial nephrectomy for complex renal cell carcinoma.

OBJECTIVES: Laparoscopic partial nephrectomy (LPN) remains challenging to even experienced laparoscopists. Complex renal tumors add an additional challenge to a minimally invasive approach to nephron-sparing surgery (NSS). We represented our technique and results of robotic partial nephrectomy (RPN) for hilar, endophytic, and multiple renal tumors. MATERIALS AND METHODS: Between May 2006 and March 2008, 29 patients with complex renal tumors underwent RPN, including hilar (n = 14), endophytic (n = 12) and multiple tumors (n = 3).The hilar vessels were clamped with laparoscopic bulldog with warm ischemia. Follow-up ranged from 3 to 23 months (mean of 15 mo). The perioperative data and pathologic results were retrospectively reviewed. RESULTS: Robotic partial nephrectomy procedures were performed successfully without complications. The mean diameter of tumors was 3.0 cm (range 2.0-4.0). The mean operative time was 197 minutes (range 172-259), and the mean blood loss was 220 ml (range 100-370). The mean warm ischemia time (WIT) was 25 min (range 16-43). The hospital stay averaged 2.5 days (range 2-3). Histopathology confirmed clear-cell carcinoma (n = 21), chromophobe cell carcinoma (n = 4), hybrid oncocytic tumor (n = 2), oncocytoma (n = 1), and cystic renal cell carcinoma (n = 1). All cases had negative surgical margins. At the 3-23 months (mean of 15 mo) follow-up, no patients experienced a significant change of glomerular filtration rate compared to preoperative levels and there was no evidence of tumor recurrence. CONCLUSION: Robotic partial nephrectomy is a safe and feasible procedure. RPN is a preferred approach for complex renal tumors when NSS is indicated. For complex and technical challenging renal tumors, robotic assistance may provide patients the benefit of minimally invasive surgery.

siRNA targeting survivin inhibits growth and induces apoptosis in human renal clear cell carcinoma 786-O cells.

We investigated the inhibitory effect of small interfering RNA (siRNA) targeting survivin gene on cell proliferation and apoptosis in human renal clear cell carcinoma 786-O cells. qRT-PCR, immunocytochemistry, and Western Blot were used to detect Survivin gene expression in 786-O cells. Cell proliferation was determined by BrdU assay and PCNA expression. Cell apoptosis was analyzed through detection of caspase-3 activity, and the effect of survivin-siRNA on Bcl-2 gene expression was also examined. Forty-eight hours after transfection, survivin expression was markedly inhibited at the mRNA and protein level. Downregulation of survivin resulted in a significant inhibition of tumor cell growth. Caspase-3 activity showed that siRNA targeting survivin gene induced cell apoptosis in 786-O cells. Moreover, Bcl-2 protein expression was markedly inhibited by transfection with siRNA against survivin. These results indicate that siRNA targeting survivin gene can downregulate survivin gene expression in 786-O cells, inhibit growth, and induce apoptosis of renal carcinoma cells.

[Diagnostic value of lesion-directed prostate biopsy under TRUS in early detection of prostate cancer].

OBJECTIVE: To evaluate lesion-directed biopsy in improving the detection rate of early prostate cancer (PCa) and in differentiating PCa from other prostate pathological changes. METHODS: We performed TRUS-guided prostate biopsy for 95 patients suspected of PCa, each subjected to extended random biopsy plus lesion-directed biopsy, and analyzed the sonographic characteristics and pathological findings. RESULTS: PCa was detected in 35 of the patients (36.8%), including 16 hypoechoic (45.7%), 4 hyperechoic (11.4%), 10 isoechoic (28.6%) and 5 mixed hetero-echoic lesions (14.3%). Of the 35 PCa cases, 17 (46.2%) were within T2b, 70.6% (12/17) of which were detected by lesion-directed biopsy and 29.4% (5/17) by sextant biopsy, the former obviously higher than the latter (P < 0.05). CONCLUSION: Lesion-directed prostate biopsy under TRUS can significantly improve the early diagnosis of prostate cancer, increase convenience and reduce patients' pain, but is not sufficient to replace traditional sextant biopsy.