The role of lumbosacral innervating noradrenergic neurons in micturition control.

A long-standing observation is that the micturition reflex receives supraspinal descending control. Although one supraspinal nucleus (Barrington's nucleus) is identified as the pontine micturition center, it remains largely unknown whether and how other supraspinal tracts are involved in micturition control. Here, we focused on the role of lumbosacral projecting neurons located in the Locus Coeruleus (LC) in modulating micturition, since previous studies indicated that the LC is involved in controlling bladder contraction. First, by performing an AAV mediated retrograde labeling using a TH-iCre mouse line, we demonstrated specific targeting of LC noradrenergic neurons innervating the lumbosacral spinal cord with high efficiency. Next, by lumbosacral injection of a retro-AAV carrying Cre-dependent human diphtheria toxin receptors (DTR), we achieved specific ablation of LC NA+ neurons with lumbosacral projections upon the administration of diphtheria toxin. Our results showed that specific ablation of theseneurons led to overflow incontinence leaks and lower void efficiency. Mechanistically, by performing the urodynamics analysis, we showed that ablation of lumbosacral innervating NAneurons resulted in detrusor-sphincter dyssynergia. Taken together, our study provided novel insights into the underlying mechanisms of supraspinal control of micturition reflex and thus shed light on developing novel treatment to improve micturition control in patients with SCI or lower urinary tract symptoms.

Fluoxetine, a selective serotonin reuptake inhibitor used clinically, improves bladder function in a mouse model of moderate spinal cord injury.

After spinal cord injury, the upward conduction of the spinal cord is lost, resulting in the loss of micturition control, which manifests as detrusor sphincter dyssynergia and insufficient micturition. Studies have shown that serotonergic axons play important roles in the control of the descending urination tract. In this study, mouse models of moderate spinal cord contusions were established. The serotonin agonists quipazine (0.2 mg/kg), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DAPT, 0.1 mg/kg), buspirone (1 mg/kg), sumatriptan (1 mg/kg), and rizatriptan (50 mg/kg), the serotonin reuptake inhibitors fluoxetine (20 mg/kg) and duloxetine (1 mg/kg), and the dopamine receptor agonist SKF-82197 (0.1 mg/kg) were intraperitoneally administered to the model mice 35 days post-injury in an acute manner. The voided stain on paper method and urodynamics revealed that fluoxetine reduced the amount of residual urine in the bladder and decreased bladder and external urethral sphincter pressure in a mouse model of moderate spinal cord injury. However, fluoxetine did not improve the micturition function in a mouse model of severe spinal cord injury. In contrast, the other serotonergic drugs had no effects on the micturition functions of spinal cord injury model mice. This study was ethically approved by the Institutional Animal Care and Use Committee of Jiangsu Province Hospital of Chinese Medicine (approval No. 2020DW-20-02) on September 11, 2020.

Transurethral assistant transumbilical laparoendoscopic single-site radical prostatectomy.

The laparoendoscopic single-site (LESS) technique is the latest technical innovation in laparoscopic surgery to undergo exponential development in urology. This study undertaken to illustrate our initial experience LESS radical prostatectomy (RP) and analyze early outcomes. Nineteen patients diagnosed with prostate cancer underwent LESS-RP in our institute. The patients were divided into two groups: conventional LESS and transurethral assistant LESS. Preoperative, perioperative, postoperative, pathologic, and functional outcomes data were assessed. With the help of a transurethral assistant, the mean operation and anastomosis time were decreased markedly. No focal positive margins were encountered. No prostate-specific antigen recurrence was detected 1 month postoperatively. Complete continence recovery (no pad) was observed in 32% of the patients at 1 month after the operation. No intraoperative and postoperative complications were reported. LESS-RP is a feasible and effective surgical procedure for treatment of prostate cancer. Moreover, transurethral assistant LESS could reduce the difficulty of LESS-RP and shorten the operation time.

[Updated treatments of castration-resistant prostate cancer].

The diagnosis and treatment of prostate cancer are being improved due to the popularized screening of prostate specific antigen. Advanced prostate cancer, in spite of its response to androgen deprivation therapy, may finally develop into castration-resistant prostate cancer (CRPC) and shorten the overall survival of the patients. Many efforts have been made by worldwide researchers for new approaches to the management of CRPC, including new hormonal therapy, cytotoxic chemotherapy, immunotherapy, and bone metastasis-targeted therapy. This paper reviews the emerging agents undergoing clinical evaluation and drugs that have received approval for the treatment of CRPC in order to provide doctors and patients with more treatment options for CRPC and improve the overall survival rate and quality of life of the patients.

[Efficacy and safety of Saw Palmetto Extract Capsules in the treatment of benign prostatic hyperplasia].

OBJECTIVE: To assess the efficacy and safety of Saw Palmetto Extract Capsules in the treatment of benign prostatic hyperplasia (BPH). METHODS: We conducted a multi-centered open clinical study on 165 BPH patients treated with Saw Palmetto Extract Capsules at a dose of 160 mg qd for 12 weeks. At the baseline and after 6 and 12 weeks of medication, we compared the International Prostate Symptom Scores (IPSS), prostate volume, postvoid residual urine volume, urinary flow rate, quality of life scores (QOL), and adverse events between the two groups of patients. RESULTS: Compared with the baseline, both IPSS and QOL were improved after 6 weeks of medication, and at 12 weeks, significant improvement was found in IPSS, QOL, urinary flow rate, and postvoid residual urine. Mild stomachache occurred in 1 case, which necessitated no treatment. CONCLUSION: Saw Palmetto Extract Capsules were safe and effective for the treatment of BPH.

Treatment of large impacted proximal ureteral stones: randomized comparison of minimally invasive percutaneous antegrade ureterolithotripsy versus retrograde ureterolithotripsy.

OBJECTIVE: To provide appropriate evidence for treatment planning of patients with an impacted proximal ureteral stones ≥1.5 cm in size, by analyzing the therapeutic outcomes for those undergoing minimally invasive percutaneous antegrade ureterolithotripsy and retrograde ureterolithotripsy. PATIENTS AND METHODS: From September 2010 to November 2011, eligible patients with impacted proximal ureteral stones ≥1.5 cm in size referred to our institute were considered for this study. The closed envelope method was used to randomize the enrolled patients to mini-PCNL (30) or retrograde ureterolithotripsy (29). The efficiency quotient (EQ) was calculated to specifically address the efficiency for both the techniques. All preoperative and postoperative data for both groups were recorded. RESULTS: The initial stone-free rate was 93.3% in the mini-PCNL group and 41.4% in the URSL group (p < 0.001). However, the overall stone-free rate at the 1-month follow-up visit after initial treatment was 100% in the mini-PCNL group and 89.7% in the URSL group (p = 0.07). The EQs for the mini-PCNL and URSL groups were 0.83 and 0.50, respectively. CONCLUSIONS: Our study shows that mini-PCNL removal of large impacted proximal ureteral calculi can achieve higher stone-free rates and safe.

[Quercetin induces the apoptosis of human PC-3 cells].

OBJECTIVE: To study the effect of quercetin on the apoptosis of human PC-3 cells. METHODS: Human PC-3 cells were cultured in vitro and then treated with quercetin at the concentrations of 50, 100, 150, 200 and 250 micromol/L. The inhibition rate of quercetin on the PC-3 cells was detected by MTT, the apoptosis of the cells determined by flow cytometry, and the changes of the cellular ultramicrostructure observed by transmission electron microscopy. RESULTS: Quercetin markedly inhibited the proliferation of PC-3 cells in vitro in a time- and dose-dependent manner. Its inhibition rates were (3.01 +/- 1.32)%, (4.84 +/- 1.73)%, (20.35 +/- 1.30)%, (16.78 +/- 1.89)% and (27.25 +/- 4.01)% at 24 hours, and (10.18 +/- 1.16)%, (6.22 +/- 0.04)%, (24.29 +/- 4.19)%, (22.4 +/- 4.26)% and (41.42 +/- 5.43)% at 48 hours in the 50, 100, 150, 200 and 250 micromol/L groups, respectively, with statistical significance at the concentration of > 150 micromol/L (P < 0.05). Flow cytometry showed that the apoptosis of PC-3 cells was increased with the elevated concentration and prolonged time of Quercetin treatment, (19.10 +/- 0.28)% and (26.55 +/- 0.78)% at 24 hours, and (27.65 +/- 1.06)% and (38.30 +/- 5.96)% at 48 hours in the 150 and 200 micromol/L groups, respectively (P < 0.05). Typical changes in the morphology of the cells were observed under the transmission electron microscope. CONCLUSION: Quercetin can inhibit the proliferation and induce the apoptosis of human PC-3 cells, but its action mechanism remains to be further investigated.

[Integrated therapy of traditional Chinese and Western medicine for BPH with diabetes mellitus: clinical observation of 52 cases].

OBJECTIVE: To investigate the effect of the integrated therapy of traditional Chinese and Western medicine in the treatment of BPH complicated by diabetes mellitus. METHODS: Fifty-two cases of BPH complicated by diabetes mellitus were equally randomized to a treatment group and a control group, and both underwent transurethral plasmakentic vaporization when fasting glucose was kept at 6.0 - 8.0 mmol/L, followed by anti-infection, rehydration and semeiologically supportive therapies. And both of the two groups received Chinese medicinal herbal treatment before and after surgery. RESULTS: Neither of the two groups showed postoperative electrolyte disturbance, ketone acidosis, or hypoglycemia. The incidences of postoperative constipation, bladder convulsion and urinary tract infection were significantly lower in the treatment group than in the control group (P < 0.05). CONCLUSION: The integrated therapy of traditional Chinese and Western medicine for BPH with diabetes mellitus can not only smoothly tide the patients over the perioperative period, but also improve their quality of life by reducing postoperative constipation, bladder convulsion and urinary tract infection.

Purification and characterization of biologically active recombinant human Eppin expressed in Escherichia coli.

BACKGROUND: Eppin (epididymis protease inhibitor) appears to play an important role in primate fertility. However, the function of Eppin and its antibody in men and its relationship with men's infertility are poorly studied. To reveal the significance and possibility of detection of anti-Eppin antibody in clinical infertilty cases, we developed an Escherichia coli expression system for the expression of biologically active human Eppin. METHODS: The human Eppin gene was cloned into PET-28a( )+ vector after induction with 0.5 mmol/L isopropy-beta-D-thiogalactoside (IPTG) at 26 degrees C for 4 hours, and the expressed fusion protein His6-Eppin was purified by Ni2+ affinity chromatography. Afterwards, six female 8-week-old Balb/c mice were immunized with purified His6-Eppin for three weeks. Their sera were collected and polyclonal antibodies against His6-Eppin were purified, all of which were further verified by Western-blot and immunofluorescence analysis. RESULTS: About 18.33 mg His6-Eppin was obtained from 1-L flask culture. The produced polyclonal antibodies against His6-Eppin recognized the Eppin protein both in human epididymis and in HEK293T cells by over-expression of the recombinant human Eppin. CONCLUSION: The purified His6-Eppin protein has biological activity, which might be a candidate for clinical diagnosis of infertility and development of male immuno-contraceptive agents.

[A proteomic study of the serum proteins in BPH and HGPIN patients].

OBJECTIVE: To evaluate two-dimensional gel electrophoresis (2DGE) and mass spectrometry in the studies of the serum proteins expressed in patients with BPH and those with high-grade prostatic intraepithelial neoplasm (HGPIN). METHODS: We extracted serum proteins from BPH and HGPIN patients by 2DGE and cut the differentially expressed interesting protein spots from the gel. Then we digested the proteins, obtained the peptide mass fingerprint by mass spectrometry and identified the proteins through database retrieval. RESULTS: We successfully achieved the 2DGE maps of the serum proteins from the BPH and HGPIN patients, obtained 1 421-1 532 protein spots from the 2D map of HGPIN and 1 466-1 778 from that of BPH. Based on peptide mass fingerprinting, 9 of the protein spots were identified. Serum amyloid A was found to be expressed in the HGPIN group, but weakly or not at all in the BPH. CONCLUSION: Proteomics can be applied to the study of the serum proteins in BPH and HGPIN patients. It can afford experimental evidence for the early diagnosis and development HGPIN, promote the search of functional and specific proteins of prostate diseases and shed new light on the network mechanisms of the problems.

[TUBVP and HOLEP: desirable surgical options for large benign prostatic hyperplasia ( >80 ml)].

OBJECTIVE: To compare the safety and efficacy of the two surgical alternatives, transurethral bipolar vaporization resection of the prostate (TUBVP) and holmium laser enucleation of the prostate (HOLEP), in the treatment of large benign prostatic hyperplasia (BPH). METHODS: Retrospective analyses were made of 56 cases of large BPH ( >80 ml), 34 treated by TUBVP with the Bipolar Vaporization System (ACMI Medical Ltd, U.K.) at 160 W in cutting and 80 W in coagulation mode, and 22 by HOLEP with the Holmium Laser System (LUMNIS Ltd, US) at 100W. The safety and efficacy of the two approaches were assessed based on the operative and follow-up data. RESULTS: Blood loss was significantly less in the HOLEP than in the TUBVP group ( P < 0.01), but the time of postoperative bladder irrigation and catheter indwelling was obviously shorter in the latter. IPSS, Qmax and Residual unine were markedly improved at 1 and 3 months after the surgery, with no statistically significant differences between the two groups. CONCLUSION: Both TUBVP and HOLEP are safe and effective surgical options for the treatment of large BPH. Particularly the former, easier to be popularly applied, is promising to be a new "gold standard" in the surgical treatment of BPH.

[Clinical value of CK34BE12 combining the expression of protein P53 gene and prostate specific antigen for the differential diagnosis of prostate carcinoma].

OBJECTIVE: To improve the level of clinical diagnosis and differential diagnosis of benign and malignant prostate lesions. METHODS: One hundred and nine cases of prostate cancer and prostate hyperplasia were evaluated by the expression of high molecular weight cytokeratin (CK34BE12), prostate specific antigen (PSA) and protein P53 gene using the immunohistochemical technique. RESULTS: The basal-cells in all of the benign lesions were stained with the CK34BE12 and PSA, while it had not immunoreactivity with P53. In contrast, the prostate carcinoma were not stained or partly stained with the CK34BE12 and PSA, but P53 show significant immunoreactivity with the tissue. CONCLUSION: Based on the routine histological studies with the expression of CK34BE12 and PSA together, they can indicate the existence of basal-cell distinctly and show indirectly whether the basal-cell is integrated. Combining the expression of P53 to determine the existence of cancer gene, it can help to distinguish benign and malignant prostate lesions.

[Clinical application of alpha1 adrenoceptor antagonist Naftopidil to the treatment of chronic non-bacterial prostatitis].

OBJECTIVE: To study the efficacy and safety of alpha1 adrenoceptor antagonist Naftopidil in the treatment of chronic non-bacterial prostatitis. METHODS: An opened, self-controlled, multicentral clinical trial was conducted. One hundred and six cases of patients who had been diagnosed as chronic non-bacterial prostatitis (NBP) were treated with Naftopidil (25 mg once a day) for 4 weeks. The efficacy was evaluated by the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and the WBC in the examination of prostatic secretion (EPS) after the treatment. RESULTS: After 4 weeks therapy, 105 cases were evaluable. After treatment, NIH-CPSI total score were averagely decreased 12.0 points (P <0.001), symptom score 7.9 points (P <0.001) and QOL score 4.1 points (P <0.001). There was a statistically significant difference in WBC count ([(15.2 +/- 15.1)/HP vs (9.5 +/- 12.0)/HP, P < 0.01] and max flow rate(MFR) [(19.2 +/- 4.8) ml/s vs (22.7 +/- 4.9) ml/s, P < 0.01]. The total effective rate were 84.8% in the whole group. The clinical adverse rate was 3.81%, including 3 cases of mild dizziness and 1 case of mild inappetence. CONCLUSION: alpha1 adrenoceptor antagonist Naftopidil is effective and safe for the treatment of chronic non-bacterial prostatitis.