Role of calcifying nanoparticles in the development of testicular microlithiasis in vivo.

BACKGROUND: Calcifying nanoparticles (NPs) have been proven to be associated with a variety of pathological calcification and previously detected in semen samples from patients with testicular microlithiasis (TM). The present study was designed to test the hypothesis if human-derived NPs could invade the seminiferous tubules and induce TM phenotype. METHODS: The animals were divided into three groups. Normal saline (0.2 mL) was injected into the proximal right ductus deferens in group A as a control group. The experimental groups, B and C received Escherichia coli (106 cfu/mL, 0.2 mL) and human-derived NPs suspension (0.2 mL), respectively. Rats were euthanized in 2 batches at 2 and 4 weeks. Testicular pathology, ultrastructure and inflammatory mediators were assessed. RESULTS: Chronic inflammatory changes were observed at 2 weeks in both groups B and C. Moreover, the innermost layer of sperm cells were structurally impaired and a zone of concentrically layered collagen fibers around the human NPs body was formed in the lumen of the seminiferous tubule in group C only, in which TM phenotype of remarkable calcification surrounded by cellular debris within the seminiferous tubules was built at 4 weeks. CONCLUSIONS: The results obtained from our study suggested a potential pathogenic effect of NPs in the development of calcification within the seminiferous tubules, which should be addressed in the future studies.

Ginkgolide B Inhibits Human Bladder Cancer Cell Migration and Invasion Through MicroRNA-223-3p.

BACKGROUND/AIMS: Ginkgolide B (GB) is currently used as an anticancer drug for treatment of some malignant cancers. However, whether it may have therapeutic effects on bladder cancer remains unknown. Here, we studied the effects of GB on bladder cancer cells. METHODS: Bladder cells were treated with different doses of GB, and the effects on ZEB1 and microRNA-223-3p (miR-223-3p) were analyzed by RT-qPCR and/or Western blot. Prediction of a regulatory relationship between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. RESULTS: We found that GB dose-dependently decreased ZEB1 protein, but not mRNA, in bladder cancer cells, resulting in suppression of cell invasion. Moreover, in bladder cancer cells, GB dose-dependently decreased the levels of miR-223-3p, which suppressed the protein translation of ZEB1 through binding to 3'-UTR of ZEB1 mRNA. Overexpression of miR-223-3p decreased ZEB1 protein, while depletion of miR-223-3p increased ZEB1 protein in bladder cancer cells. CONCLUSION: GB inhibits bladder cancer cell invasiveness through suppressing ZEB1 protein translation via upregulating miR-223-3p.

Expression of heat shock protein 27 correlates with actin cytoskeletal dynamics and contractility of cultured human bladder smooth muscle cells.

Heat shock protein 27 (HSP27) is one of the most important chaperone proteins that modulates smooth muscle contraction. Here we investigated the effects of HSP27 expression on cytoskeleton dynamics and contractile function of human bladder smooth muscle cells (BSMCs) in vitro. Cultured human BSMCs were transfected with lentiviral vectors expressing either HSP27 or HSP27-siRNAs. Normal BSMCs cells and cells transfected with the empty lentivirus were used as control. Cells were then cultured on Flexcell flexible membrane dishes and mechanical stretch (14.8% elongation) was applied. The stretch caused significant disruption of actin cytoskeletal structure and decrease in F/G-actin ratio in BSMCs with HSP27 over-expression, knock-down and control groups (P<0.05) as indicated by phalloidin-FITC staining. It was also shown that the structure of actin filaments in HSP27 over-expressed cells recovered and F/G-actin ratio significantly increased at 12h after stretching compared to unstretched cells (P<0.05), but not in HSP27 knock-down cells, suggesting that HSP27 promoted the recovery of cytoskeletal structure in BSMCs from stretch-induced injury. In addition, the contractile force of BSMCs was enhanced by over-expression of HSP27 and attenuated by knock-down of HSP27 (P<0.05), suggesting a pivotal role of HSP27 in regulating bladder smooth muscle contraction.

Urethral orifice hyaluronic acid injections: a novel animal model of bladder outlet obstruction.

BACKGROUND: We produced a novel model of bladder outlet obstruction (BOO) by periurethral injection of hyaluronic acid and compared the cystometric features, postoperative complications, and histopathological changes of that model with that of traditional open surgery. METHODS: Forty female Sprague-Dawley rats were divided into three groups. Fifteen rats were subcutaneously injected with 0.2 ml hyaluronic acid at 5, 7, and 12 o'clock around the urethral orifice. Another fifteen rats underwent traditional open partial proximal urethral obstruction surgery, and 10 normal rats used as controls. After 4 weeks, filling cystometry, postoperative complications, and histopathological features were evaluated in each group. Three rats were also observed for 12 weeks after hyaluronic acid injection to evaluate the long-term effect. RESULTS: Hyaluronic acid periurethral injection caused increased maximum cystometric capacity, maximum bladder pressure, micturition interval, and post-void residual urine volume compared with control (p < 0.01). The injection group had significantly shorter operative time, less incidence of incision infection and bladder stone formation compared with the surgery group (p < 0.01). Hematoxylin and eosin (HE) staining showed suburothelial and interstitial hyperemia edema and smooth muscle hypertrophy in both injection and surgery bladders; these were not observed in the control group. Bladder weight and thickness of smooth muscle in the injection and surgery groups were significantly greater than those in the control group (p < 0.01). Urethral epithelial hyperplasia and lamina propria inflammation were observed in the surgery group but not in the injection or control groups. Rats periurethrally injected hyaluronic acid were stable the compound was not fully absorbed in any rat after 12 weeks. CONCLUSIONS: Hyaluronic acid periurethral injection generates a simple, effective, and persistent animal model of BOO with lower complications, compared with traditional surgery.

Expression of Hsp27 correlated with rat detrusor contraction after acute urinary retention.

Heat shock protein 27 (Hsp27) can regulate actin cytoskeleton dynamics and contractile protein activation. This study investigates whether Hsp27 expression is related to bladder contractile dysfunction after acute urinary retention (AUR). Female rats were randomized either to AUR by urethral ligation or to normal control group. Bladder and smooth muscle strip contraction at time points from 0 h to 7 days after AUR were estimated by cystometric and organ bath studies. Hsp27 expression in bladder tissue at each time point was detected with immunofluorescence, Western blots, and real-time PCR. Expression of the three phosphorylated forms of Hsp27 was detected by Western blots. Smooth muscle ultrastructure was observed by transmission electron microscopy. Data suggest that maximum detrusor pressure and both carbachol-induced and spontaneous detrusor strip contraction amplitude decreased gradually for the duration from 0 to 6 h, and then increased gradually to near-normal values at 24 h. Treatment of muscle strips with the p38MAK inhibitor, SB203580, inhibited carbachol-induced contractions. Smooth muscle ultrastructure damage was the highest at 6 h after AUR, and then lessened gradually during next 7 days, and ultrastructure was close to normal. Expressions of Hsp27 mRNA and protein and the proteins of the three phosphorylated forms were higher at 0 h, decreased to lower levels up to 6 h, and then gradually increased. Therefore, we conclude that rat bladder contractile function after AUR worsens during 0-6 h, and then gradually recovers. The findings of the current study suggest that Hsp27 modulates bladder smooth muscle contraction after AUR, and that phosphorylation of Hsp27 may be an important pathway modulating actin cytoskeleton dynamics in bladder smooth muscle contraction and reconstruction after injury.

Glutathione S-transferases gene polymorphisms and risk of male idiopathic infertility: a systematic review and meta-analysis.

The Glutathione S-transferases (GSTs) polymorphisms have been implicated in susceptibility to male idiopathic infertility, but study results are still controversial. To investigate the genetic associations between GSTs polymorphisms and risk of male idiopathic infertility, a systematic review and meta-analysis were performed. Meta-analysis was performed by pooling odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) form studies in electronic databases up to March 16, 2012. Glutathione S-transferase M 1 (GSTM1) null genotype, Glutathione S-transferase T 1 (GSTT1) null genotype, and dual null genotype of GSTM1/GSTT1 were analyzed independently. 14 eligible studies with a total of 1,845 idiopathic infertility males and 1,729 controls were included. There were 13 studies on GSTM1 polymorphism, 10 ones on GSTT1 polymorphism and 5 ones on GSTM1-GSTT1 interaction analysis. Meta-analyses of total relevant studies showed GSTM1 null genotype was significantly associated with an increased risk of male idiopathic infertility (OR = 1.40, 95 % CI 1.07-1.84, P OR = 0.015). The GSTM1-GSTT1 interaction analysis showed dual null genotype of GSTM1/GSTT1 was also significantly associated with increased risk of male idiopathic infertility (OR = 1.85, 95 % CI 1.07-3.21, P OR = 0.028). Subgroup analyses by ethnicity showed the associations above were still statistically significant in Caucasians (For GSTM1, OR = 1.51, 95 % CI 1.11-2.05, P OR = 0.009; For GSTM1/GSTT1, OR = 2.10, 95 % CI 1.51-2.91, P OR < 0.001). This meta-analysis suggests GSTM1 null genotype contributes to increased risk of male idiopathic infertility in Caucasians, and males with dual null genotype of GSTM1/GSTT1 are particularly susceptible to developing idiopathic infertility.

Long-term evaluation of patients undergoing genitoplasty due to disorders of sex development: results from a 14-year follow-up.

PURPOSE: To summarize the experience in treating patients with genitoplasty due to disorders of sex development in China. METHODS: The operative procedures, gender of rearing, surgical outcome, and psychosocial and family adjustments of 262 patients were reviewed retrospectively. RESULTS: At initial diagnosis, the mean age was 14.3 ± 2.8 years (range: 2-38 years). There were 96 children, 133 adolescents, and 33 adults. Follow-up was done every 6 months. Patients with female sex assignment had no urinary incontinence or voiding difficulty. Five patients underwent the second surgery (3%); vaginal dilation was performed in 35 patients with postoperative vaginal stenosis; 12 patients (7.4%) were unsatisfactory with the outcome. For patients with male sex assignment, the median length of penis was 2.2 cm in prepubertal patients, 4.2 cm in pubertal patients, and 5.0 cm in adults; 39 patients developed postvoid dribbling (39%); 21 patients underwent a second surgery (21%); urethral dilation was done in 28 patients (28%) due to urethral stricture; 38 patients were unsatisfactory with the outcome (38%). In addition, 136 patients (83%) with female sex assignment and 54 (54%) with male sex assignment had favorable psychosocial adjustment. CONCLUSIONS: Patients with male sex assignment have more surgical complications and difficulties in psychosocial adjustment as compared to those with female sex assignment.

Radiomics Analysis of Breast Lesions in Combination with Coronal Plane of ABVS and Strain Elastography.

Background: Breast cancer is the most common tumor globally. Automated Breast Volume Scanner (ABVS) and strain elastography (SE) can provide more useful breast information. The use of radiomics combined with ABVS and SE images to predict breast cancer has become a new focus. Therefore, this study developed and validated a radiomics analysis of breast lesions in combination with coronal plane of ABVS and SE to improve the differential diagnosis of benign and malignant breast diseases. Patients and Methods: 620 pathologically confirmed breast lesions from January 2017 to August 2021 were retrospectively analyzed and randomly divided into a training set (n=434) and a validation set (n=186). Radiomic features of the lesions were extracted from ABVS, B-ultrasound, and strain elastography (SE) images, respectively. These were then filtered by Gradient Boosted Decision Tree (GBDT) and multiple logistic regression. The ABVS model is based on coronal plane features for the breast, B+SE model is based on features of B-ultrasound and SE, and the multimodal model is based on features of three examinations. The evaluation of the predicted performance of the three models used the receiver operating characteristic (ROC) and decision curve analysis (DCA). Results: The area under the curve, accuracy, specificity, and sensitivity of the multimodal model in the training set are 0.975 (95% CI:0.959-0.991),93.78%, 92.02%, and 96.49%, respectively, and 0.946 (95% CI:0.913 -0.978), 87.63%, 83.93%, and 93.24% in the validation set, respectively. The multimodal model outperformed the ABVS model and B+SE model in both the training (P < 0.001, P = 0.002, respectively) and validation sets (P < 0.001, P = 0.034, respectively). Conclusion: Radiomics from the coronal plane of the breast lesion provide valuable information for identification. A multimodal model combination with radiomics from ABVS, B-ultrasound, and SE could improve the diagnostic efficacy of breast masses.

Human telomerase reverse transcriptase transfection reduces apoptosis in human penile smooth muscle cells and slows down cellular aging.

INTRODUCTION: Erectile dysfunction (ED) is one of the most common diseases in male urology that greatly affects the quality of life in senior people. Relaxation of corpus cavernosum smooth muscle is the key to penile erection. AIM: To explore effects of human telomerase reverse transcriptase (hTERT) gene transfection on biological behaviors of human penile smooth muscle cells. METHODS: Human penile smooth muscle cells were grown in primary culture. A fluorescent eukaryotic expression vector, hTERT-internal ribosome entry site 2 (IRES2)-enhanced green fluorescent protein (EGFP), was constructed and transfected into human penile smooth muscle cells using Lipofectin reagent. MAIN OUTCOME MEASURE: The telomerase activity, mitotic index, cell apoptosis, and cell growth curves of transfected smooth muscle cells were determined; the potential formation of malignant phenotypes in these transfected cells was investigated. RESULTS: Telomerase activity, mitotic index, and cell growth of hTERT-transfected cells were significantly higher than those of nontransfected cells and cells transfected with the empty EGFP vector, while apoptosis rates were the lowest in hTERT-transfected cells. No changes in cell morphology, chromosome number, and tumorigenicity were observed between hTERT-transfected cells and control cells. CONCLUSION: In this study, for the first time, the hTERT gene was transfected into human penile smooth muscle cells, and the gene increased telomerase activity in cells, reduced cell apoptosis, and slowed down cell aging. We believe that this finding is of potential clinical value in the prevention and treatment of organic ED.

Prulifloxacin versus levofloxacin in the treatment of respiratory and urinary tract infections: a multicentre, double-blind, randomized controlled clinical trial.

BACKGROUND: Prulifloxacin is a promising fluoroquinolone antibiotic. A multicentre, double-blind, randomized clinical study was designed to evaluate its efficacy and safety compared to that of levofloxacin for the treatment of respiratory and urinary infections of Chinese patients. METHODS: A total of 267 patients were enrolled and each was randomly assigned to either the treatment or the control group. Prulifloxacin 264.2 mg (equivalent to ulifloxacin 200 mg) b.i.d. or levofloxacin hydrochloride 200 mg b.i.d. was administered orally for 5-14 days according to a patient's condition. The clinical response, bacterial eradication and incidence of adverse events were evaluated. RESULTS: Two hundred and forty-three patients completed the study. For the modified intention-to-treat population, the cure and effective rates were 45.53 and 82.93% in the prulifloxacin group and 49.18 and 83.61% in the levofloxacin group. For the per-protocol analysis population, the cure and effective rates were 45.90 and 83.61% in the prulifloxacin group and 49.59 and 83.47% in the levofloxacin group. The bacterial eradication rates were 96.59 and 95.35%, and the drug-related adverse event rates were 7.87 and 5.51% in the prulifloxacin and levofloxacin group, respectively. The cure rate and efficacy rate of respiratory and urinary tract infections of the levofloxacin group were better than those of the prulifloxacin group. However, the difference between the 2 groups was not statistically significant (p > 0.05). CONCLUSION: Prulifloxacin is as effective and well tolerated as levofloxacin in the treatment of respiratory and urinary tract infections.

Chemical irritation of the prostate sensitizes P(2)X(3) receptor-mediated responses in rat dorsal root ganglion neurons.

AIMS: P(2)X(3) (ATP-gated receptors) in nociceptive neurons of dorsal root ganglion (DRG) participate in transmission of pain signals from the periphery to the spinal cord. However, the role of P(2)X(3) receptors in chronic prostate pain and continued intractable pain remains unclear. MATERIALS AND METHODS: We examined ATP-evoked responses and P(2)X(3) expression in DRG neurons isolated from rats with prostatic inflammation induced by injection of complete Freund's adjuvant (CFA) into the prostate. Neurons were dissociated from the L(6)-S(1) DRG. The effect of ATP on the excitability of DRG neurons was determined using whole-cell patch clamp. P(2)X(3) receptor expression was determined with Western blot on the 3rd and 10th days after irritation of the prostate. RESULTS: Although application of ATP induced both fast- and slow-inactivating currents and caused depolarization in control and inflamed neurons, compared to the control group, the increase in ATP responses gave rise to large depolarization that exceeded the threshold of action potentials in inflamed DRG neurons. The affinity of P(2)X(3) receptor for ATP increased significantly and inflammation enhanced the expression of P(2)X(3) receptor in inflamed neurons. CONCLUSIONS: P(2)X(3) receptor upregulation could account for neuronal hypersensitivity and contribute to abnormal pain responses associated with chronic prostatitis. These results suggest that P(2)X(3) receptors are useful targets for the treatment of pain in chronic prostatitis.

Specific management of acute renal failure caused by an upper ureteral stone in a solitary pelvic kidney.

A 36-year-old man presented with left lumbosacral region pain and 2 days of oliguria. Acute renal failure of a solitary pelvic kidney was diagnosed after a blood creatinine test, color Doppler ultrasonography, and magnetic resonance imaging. The cause of the acute renal failure was not clear; however, acute ureteral obstruction was presumed and emergency surgery was performed. The unusual anatomy of the kidney required specific management to find and relieve the cause of the obstruction. We found and cleared an upper ureteral stone by endoscopic surgery after exploring the kidney through open surgery.

Caveolin-1 may participate in the pathogenesis of bladder pain syndrome/ interstitial cystitis.

OBJECTIVES: To determine whether caveolin-1 expression is associated with bladder pain syndrome/interstitial cystitis (BPS/IC) and to better understand the pathogenesis of BPS/IC. METHODS: The study population was composed of 19 women with BPS/IC and 7 healthy women as controls. Midstream urine specimens were collected before cystoscopy and cold cup bladder biopsies were obtained from the trigone of the bladder. Caveolin-1 protein expression was determined by indirect immunofluorescence and Western blot analysis in cases and controls, using a rabbit polyclonal antibody against caveolin-1. χ(2) test and Student's t test were used in the statistical analysis. RESULTS: A statistical difference of caveolin-1 protein expression was observed between BPS/IC and healthy controls (p < 0.05, χ(2) test). Western blot analysis showed that the mean relative integrated density value of caveolin-1 in (BPS/IC) patients was significantly higher than that in the control group (p < 0.001, Student's t test). CONCLUSIONS: The results of our study demonstrate that there is a relationship between the raised levels of caveolin-1 expression and BPS/IC. This preliminary study may provide a basis for further investigation of the role of caveolin-1 in the pathogenesis of BPS/IC.

A modified single-port technique for the minimally invasive treatment of pediatric inguinal hernias with high ligation of the vaginal process: the initial experience.

The aim of this study is to evaluate a modified single-port technique for treating pediatric inguinal hernias (PIH) with high ligation of the vaginal process by combining the use of a ureteroscope and a custom-made puncture guide under pneumoperitoneum. The cases of 86 patients with PIH who underwent the procedure in our institution were reviewed. All of the operations were completed uneventfully. The median operative times for unilateral and bilateral lesions were 11 min (range, 8-15 min) and 16 min (range, 12-20 min), respectively. All of the patients were discharged from the hospital on the day of surgery. No massive hemorrhages or infections were reported. The median follow-up was 15 months (range, 12-24 months), during which no recurrences were reported. In conclusion, with the aid of a ureteroscope and a modified custom-made puncture suit, the described single-port technique allowed easier induction of the ligation suture and a shorter operative time than other methods reported previously. However, the determination of long-term efficacy requires additional studies with larger sample sizes and longer follow-up times.

Decreased nanobacteria levels and symptoms of nanobacteria-associated interstitial cystitis/painful bladder syndrome after tetracycline treatment.

INTRODUCTION AND HYPOTHESIS: This study was designed to detect whether nanobacteria (NB) reside in urine and bladder tissue samples of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) and whether antibiotic therapy targeting these organisms is effective in reducing NB levels and IC/PBS symptoms. METHODS: Twenty-seven IC/PBS patients underwent cystoscopy. Bladder biopsies and urine samples were obtained and cultured for NB, which were identified by indirect immunofluorescent staining and transmission electron microscopy. RESULTS: Eleven bladder samples showed growth of microbes that were identified to be similar to NB. Homologous study of the 16S ribosomal RNA gene suggested that the NB could be the pathogen. For enrolled 11 patients, NB levels decreased dramatically after tetracycline treatment, and they reported significant reduction in the severity of IC/PBS symptoms. CONCLUSIONS: A high prevalence of NB was observed in female IC/PBS, and anti-NB treatment effectively improved the symptoms, which suggest that NB may cause some cases of IC/PBS.

[Correlation between activation of L5-S2 spinal cord astrocytes and effect of substance P in chronic prostatitis pain].

OBJECTIVE: To observe the expressions of the substance P (SP) mRNA and neurokinin-1 receptor (NK-1R) in the posterior horn of the L5 - S2 spinal cord in the rat model of chronic prostatitis pain, and to investigate the changes in the activation of astrocytes and influence of SP on this activation in rat spinal cord astrocytes cultured in vitro. METHODS: The rat model of chronic prostatitis pain was established by injection of complete Freund's adjuvant (CFA) and assessed by the tail flick threshold test, the control rats injected with sodium chloride and all observed at 0, 14 and 28 days. Changes in the expressions of SP mRNA, NK-1R, glial fibrillary acidic protein (GFAP), tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) in the posterior horn of the L5 - S2 spinal cord were detected by RT-PCR and Western blot. Rat spinal cord astrocytes were cultured in vitro and divided into a control group, cultured with ITS cell culture fluid, and two experiment groups, with Group 1 stimulated with SP at the concentration of 10(-9) - 10(-6) mol/L for 12 hours followed by determination of the expressions of TNF-alpha, IL-1beta, NO and NOS by ELISA and nitrate reductase and colorimetric methods, and Group 2 at 10(-7) mol/L for 0, 24, 48 and 72 hours followed by detection of the GFAP expression by Western blot. RESULTS: The expressions of SP mRNA, NK-1 R, GFAP, TNF-alpha and iNOS in the posterior horn of the L5 - S2 spinal cord were obviously higher in the rat prostatitis pain models than in the controls, successively higher at 28 than at 14 and 0 d (P < 0.01), and so was the expression of GFAP at 28 than at 14 d in the experiment groups (P < 0.05). SP induced a gradual increase at 10(-7) mol/L in the expression of GFAP in the spinal cord astrocytes at 0 -72 h, significantly different from that of the control group (P < 0.01), and it promoted the excretion of TNF-alpha and IL-1beta and the activity of NO and NOS at 10(-9) - 10(-6) mol/L at 12 h in a concentration-dependent manner, with marked differences between the experiment and control groups (P < 0.01, P < 0.05). But a decreased excretion of IL-1 beta was observed in the 10(-6) mol/L group, though with no significant difference from the control (P > 0.05). CONCLUSION: Chronic prostatitis pain could upregulate the expressions of the excitatory transmitter SP and receptor in the L5 - S2 spinal cord, and result in the activation of astrocytes and increased excretion of proinflammatory cytokines, which may be associated with the persistence and generalization of prostatitis pain.

Intrathecal administration of resiniferatoxin produces analgesia against prostatodynia in rats.

BACKGROUND: Prostatodynia remains a difficult clinical problem. Resiniferatoxin (RTX), an ultrapotent vanilloid, can produce a selective and long-lasting desensitization of nociception via C-fiber sensory neurons. Substance P (SP) and calcitonin gene-related peptide (CGRP) released from C-fibers are key neurotransmitters in visceral pain. In this study, we evaluated the analgesic effect of intrathecal RTX on rat prostatodynia. METHODS: Male Sprague-Dawley rats were divided into 3 groups for different treatment. In group A, sham operation was preformed. In group B, 100 microl complete Freund's adjuvant (CFA) was injected into the rat's bilateral ventral prostate to induce chronic inflammation. In group C, after prostatitis formed, 50 microl 10 nmol/L RTX was injected into the rat's lumbosacral (L5-S2) vertebral canal. SP and CGRP contents in the spinal cord were investigated by immunohistochemistry and radioimmunoassay (RIA). Their transcriptional levels in dorsal root ganglion (DRG) were determined by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, pelvic nerve afferent discharge was recorded to explore the neuro-electrophysiological mechanisms underlying RTX-induced effect. RESULTS: SP and CGRP released in the spinal cord and their synthesis in DRG were increased significantly in response to CFA-induced chronic prostatitis, whereas this increase was effectively inhibited by intrathecal RTX. Meanwhile, pelvic nerve afferent electrical activity was enhanced significantly in rats with chronic prostatitis, but it was attenuated markedly in RTX-treated rats paralleled by the change of neuropeptides. CONCLUSIONS: Intrathecal RTX administration could produce an analgesic effect on rat prostatodynia. Suppression of pelvic nerve afferent electrical activity may be a crucial mechanism underlying RTX-induced analgesia. RTX intrathecal application may present a novel analgesic strategy of prostatodynia.

Notch3 overexpression enhances progression and chemoresistance of urothelial carcinoma.

Abnormal activation of Notch signaling is involved in the etiology of various diseases, including cancer, but the association between Notch3 expression in urothelial cancer and clinical outcome remains unclear, and the molecular mechanisms underlying Notch3 signaling activation are not well defined. In this study we examined 59 urothelial cancer patients and found that Notch3 was more highly expressed in human urothelial cancer tissues than in non-tumorous bladder tissue samples, with Notch3 overexpression being associated with poor clinical outcome. Notch3 knockdown resulted in decreased proliferation of urothelial cancer cells in vitro and decreased xenograft tumor growth in vivo. In addition, Notch3 knockdown rendered urothelial cancer cells more sensitive to cisplatin. Furthermore, suberoylanilide hydroxamic acid (SAHA, a histone deacetylase [HDAC] inhibitor) induced acetylation of NOTCH3, downregulated Notch 3, prevented urothelial cancer cell proliferation, and induced cell cycle arrest. Taken together, these data suggested that Notch 3 overexpression promotes growth and chemoresistance in urothelial cancer.

Establishment of immunoassay for detecting HPV16 E6 and E7 RNA.

Cervical carcinoma is the most prevalent malignancy second only to breast cancer among women worldwide. Since more than 99% of cervical cancers are caused by human papilloma virus (HPV), measurement of HPV (HPV test) was commonly used in screening risk and/or early stage of cervical cancer as well as assessing the efficacies of the treatments that can decrease the incidence of cervical cancer. Many approaches that diagnose HPV infections have been developed, while most of them have distinct shortcomings. We here established a novel immunoassay method in which the pairs of unlabeled DNA probes firstly bind to HPV16 E6 and E7 RNAs to form the DNA-RNA hybrids, and the hybrids will subsequently be identified by S9.6 antibody. The sensitivity of this highly specific method can reach ~0.923 pg/mL and ~0.424 pg/mL of in vitro transcribed HPV16 E6 and E7 RNA, respectively, and reverse transcription and polymerase chain reaction (PCR) amplification were no longer needed. Thus, our immunoassay approaches can precisely reflect the actually viral load that is related to the course of HPV infection. In addition, it has also fast and low cost characteristic feature.