The effect of JuanBiQiangGu granules in combination with methotrexate on joint inflammation in rheumatoid arthritis: a randomized controlled trial.

Background: Rheumatoid arthritis (RA) joint inflammation severely affects joint function and quality of life in patients and leads to joint deformities and limb disability. The non-steroidal anti-inflammatory drugs used in the treatment of RA do not fully control the progression of joint inflammation and bone destruction and have notable adverse reactions. Traditional Chinese medicine formula JuanBiQiangGu Granules (JBQG) are commonly used for the treatment of RA inflammation and delay of bone destruction, but has not been evaluated through high-quality clinical studies. There is a pressing need for well-designed, randomized, parallel, controlled clinical studies to evaluate the exact effect of JBQG on RA joint inflammation and improvement of patient quality of life. Methods: This is a randomized, parallel, controlled clinical study in which 144 patients with rheumatoid arthritis who met the inclusion criteria were randomly assigned to 2 groups in a 1:1 ratio. The JBQG group received methotrexate 7.5 mg qw and JBQG granules 8 mg tid, while the MTX group received methotrexate 7.5 mg qw. The endpoint was 12 weeks after treatment. Relevant indices at baseline, 4 weeks, 8 weeks, and 12 weeks after treatment were observed and recorded, and DAS28-ESR, HAQ-DI, and Sharp scores were recorded for each patient. Blood samples were collected to test for CRP, ESR, TNF-α, IL-1ß, IL-6, IL-17, and INF-γ, and adverse reactions and liver and kidney function (AST, ALT, Cr, BUN) were recorded for safety assessment. After 12 weeks of treatment, the effect of JBQG granules on disease activity, improvement in bone damage, and patient quality of life scores and safety in RA patients were evaluated. Results: A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators (p > 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR levels below or equal to Low, including 45.07% in Remission and 5.63% in High, compared to 53.1% in the MTX group below or equal to Low, 12.33% in Remission, and 17.81% in High. CRP was significantly reduced (8.54 ± 5.87 vs. 11.86 ± 7.92, p < 0.05, p = 0.005), ESR was significantly reduced (15.1 ± 6.11 vs. 21.96 ± 9.19, p < 0.0001), TNF-α was significantly reduced (1.44 ± 0.83 vs. 1.85 ± 1.07, p < 0.05, p = 0.011), IL-17 was significantly reduced (0.53 ± 0.33 vs. 0.71 ± 0.38, p < 0.05, p = 0.004), and INF-γ was significantly reduced (3.2 ± 1.51 vs. 3.89 ± 1.77, p < 0.05, p = 0.014). The median (IQR) OPG in the JBQG group was 2.54 (2.21-3.01), significantly higher than in the MTX group 2.06 (1.81-2.32), p < 0.0001), and the median (IQR) ß-CTX in the JBQG group was 0.4 (0.32-0.43), significantly lower than in the MTX group 0.55 (0.47-0.67), p < 0.0001). The median (IQR) VSA scores were 2 (1-3), a decrease from 3 (2-4) in the MTX group (p < 0.0001). The median (IQR) Sharp scores were 1 (1-2), a decrease from 2 (1-2) in the MTX group, but the difference was not statistically significant (p > 0.05, p = 0.28). The median (IQR) HAQ-DI scores were 11 (8-16), significantly lower than in the MTX group 26 (16-30) (p < 0.0001). The median (IQR) AST in the JBQG group was 16 (12-20), with a significant difference compared to the MTX group 19 (13-25) (p < 0.01, p = 0.004); the median (IQR) ALT in the JBQG group was 14 (10-18), with a significant difference compared to the MTX group 16 (11-22.5) (p < 0.05, p = 0.015). There were no statistically significant differences in Cr or BUN (p > 0.05). Conclusion: JuanBiQiangGu Granules can be used to treat patients with rheumatoid arthritis, alleviate joint inflammation, reduce the incidence of adverse reactions to methotrexate, and has good safety. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html; identifier: ChiCTR2100046373.

Presence of secondary bladder cancer following radical nephroureterectomy for upper tract urothelial carcinoma: characteristics, risk factors, and predictive value.

BACKGROUND: To assess the characteristics, predictive risk factors, and prognostic effect of secondary bladder cancer (SBCa) following radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). METHODS: Using the Surveillance, Epidemiology, and End Results database, the authors analyzed clinicopathologic characteristics and survival data from 472 UTUC patients with SBCa after RNU, between 2004 and 2017. Cox's proportional hazard regression model was implemented to identify independent predictors associated with post-recurrence outcomes. The threshold for statistical significance was p < 0.05. RESULTS: In total, 200 Ta-3N0M0 localized UTUC patients with complete data were finally included. With a median follow-up of 71.0 months (interquartile ranges [IQR] 36.0 -103.8 months), 52.5% (n = 105) had died, with 30.5% (n = 61) dying of UTUC. The median time interval from UTUC to SBCa was 13.5 months (IQR 6.0-40.8 months). According to multivariable Cox regression analysis, patients with SBCa located at multiple sites, advanced SBCa stage, higher SBCa grade, elderly age and a shorter recurrence time, encountered worse cancer-specific survival (CSS), all p < 0.05. CONCLUSION: For primary UTUC patients with SBCa after radical surgery, advanced age, multiple SBCa sites, shorter recurrence time, higher SBCa stage, and grade proved to be significant independent prognostic factors of CSS. We ought to pay more attention to SBCa prevention as well as to earlier signs which may increase the likelihood of early detection. Having the ability to manage what may be seen as the superficial SBCa signs may enable us to improve survival but further research is required.

The Value of Lymph Node Dissection in Patients With Node-Positive Upper Urinary Tract Urothelial Cancer: A Retrospective Cohort Study.

Purpose: The value of lymphadenectomy during radical nephroureterectomy (RNU) remains unclear. This study aimed to determine the effects of the removed lymph node (RLN) counts, positive lymph node (pLN) counts, and pLN density (pLND) on survival outcomes in patients with node-positive upper urinary tract urothelial cancer (UTUC). Methods: A total of 306 patients with node-positive UTUC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016 were identified. Multivariable Cox regression analyses were used to evaluate the effect of RLN counts, pLN counts, and pLND on survival outcomes. The maximally selected rank statistics were used to determine the most informative cutoff value for pLND on survival outcomes. Results: The RLN counts or pLN counts were not associated with survival outcomes, whereas higher pLND was associated with lower cancer-specific survival (CSS) and overall survival (OS) [hazard ratio (HR) 1.75, P = 0.014 and HR 1.62, P = 0.036, respectively]. The most informative cutoff value for pLND in relation to survival was 27%. Patients with pLND ≥27% had worse 5-year survival rates than those with pLND <27% (52.9% vs. 75.9% for CSS and 18.7% vs. 34.2% for OS, each P < 0.05). Furthermore, the multivariable Cox regression model with pLND could predict 5-year CSS (AUC 0.732 vs. 0.647) or OS (AUC 0.704 vs. 0.621) more accurately than the model without pLND. Conclusions: For patients with node-positive UTUC, more lymph nodes removed do not offer a better therapeutic effect. However, pLND provides additional prognostic value.

Correction: All-purpose nanostrategy based on dose deposition enhancement, cell cycle arrest, DNA damage, and ROS production as prostate cancer radiosensitizer for potential clinical translation.

Correction for 'All-purpose nanostrategy based on dose deposition enhancement, cell cycle arrest, DNA damage, and ROS production as prostate cancer radiosensitizer for potential clinical translation' by Xiao-xiao Guo et al., Nanoscale, 2021, 13, 14525-14537, https://doi.org/10.1039/D1NR03869A.

All-purpose nanostrategy based on dose deposition enhancement, cell cycle arrest, DNA damage, and ROS production as prostate cancer radiosensitizer for potential clinical translation.

Radiotherapy (RT) is one of the main treatments for men with prostate cancer (PCa). To date, numerous sophisticated nano-formulations as radiosensitizers have been synthesized with inspiring therapeutic effects both in vitro and in vivo; however, almost all the attention has been paid on the enhanced dose deposition effect by secondary electrons of nanomaterials with high atomic numbers (Z); despite this, cell-cycle arrest, DNA damage, and also reactive oxygen species (ROS) production are critical working mechanisms that account for radiosensitization. Herein, an 'all-purpose' nanostrategy based on dose deposition enhancement, cell cycle arrest, and ROS production as prostate cancer radiosensitizer for potential clinical translation was proposed. The rather simple structure of docetaxel-loaded Au nanoparticles (NPs) with prostate specific membrane antigen (PSMA) ligand conjugation have been successfully synthesized. Enhanced cellular uptake achieved via the selective internalization of the NPs by PCa cells with positive PSMA expression could guarantee enhanced dose deposition. Moreover, the as-synthesized nanosystem could effectively arrest the cell cycle at G2/M phases, which would reduce the ability of DNA damage repair for more irradiation sensitive of the PCa cells. Moreover, the G2/M phase arrest would further promote cascade retention and the enrichment of NPs within the cells. Furthermore, ROS generation and double strand breaks greatly promoted by NPs under irradiation (IR) could also provide an underlying basis for effective radiosensitizers. In vitro and in vivo investigations confirmed the as-synthesized NPs as an effective nano-radiosensitizer with ideal safety. More importantly, all moieties within the present nanosystem have been approved by FDA for the purpose of PCa treatment, thus making it highly attractive for clinical translation.

Comparison of Oncological Outcomes Between Radical Prostatectomy and Radiotherapy by Type of Radiotherapy in Elderly Prostate Cancer Patients.

OBJECTIVE: We aimed compare the oncologic outcomes of radical prostatectomy (RP) with those of external beam radiotherapy (EBRT), brachytherapy (BT), or EBRT + BT (EBBT) in elderly patients with localised prostate cancer (PCa). METHODS: Localised PCa patients aged ≥70 years who underwent RP, EBRT, BT, or EBBT between 2004 and 2016 were identified from the Surveillance, Epidemiology, and End Results database. Multivariable competing risks survival analyses were used to estimate prostate cancer-specific mortality (CSM) and other-cause mortality (OCM). Subgroup analyses according to risk categories were also conducted. RESULTS: Overall, 14057, 37712, 8383, and 5244 patients aged ≥70 years and treated with RP, EBRT, BT, and EBBT, respectively, were identified. In low- to intermediate-risk patients, there was no significant difference in CSM risk between RP and the other three radiotherapy modalities (all P > 0.05). The corresponding 10-year CSM rates for these patients were 1.2%, 2.3%, 2.0%, and 1.8%, respectively. In high-risk patients, EBRT was associated with a higher CSM than RP (P = 0.003), whereas there was no significant difference between RP and BT or RP and EBBT (all P > 0.05). The 10-year CSM rates of high-risk patients in the RP, EBRT, BT, and EBBT groups were 7.5%, 10.2%, 8.3%, and 7.6%, respectively. Regarding OCM, the risk was generally lower in RP than in the other three radiotherapy modalities (all P < 0.001). CONCLUSIONS: Among men aged ≥70 years with localised PCa, EBRT, BT, and EBBT offer cancer-specific outcomes similar to those of RP for individuals with low- to intermediate-risk disease. In patients with high-risk disease, EBBT had outcomes equally favourable to those of RP, but RP is more beneficial than EBRT. More high-quality trials are warranted to confirm and expand the present findings.

Advances in single-cell sequencing: insights from organ transplantation.

Single-cell RNA sequencing (scRNA-seq) is a comprehensive technical tool to analyze intracellular and intercellular interaction data by whole transcriptional profile analysis. Here, we describe the application in biomedical research, focusing on the immune system during organ transplantation and rejection. Unlike conventional transcriptome analysis, this method provides a full map of multiple cell populations in one specific tissue and presents a dynamic and transient unbiased method to explore the progression of allograft dysfunction, starting from the stress response to final graft failure. This promising sequencing technology remarkably improves individualized organ rejection treatment by identifying decisive cellular subgroups and cell-specific interactions.

In vivo hepatoprotective activity and the underlying mechanism of chebulinic acid from Terminalia chebula fruit.

BACKGROUND: The fruit of Terminalia chebula Retz. is one of the most widely used herbal drug in Traditional medicine prescriptions including those for liver diseases. In the screening of bioactive constituents that have potential hepatoprotective activity, chebulinic acid (CA) which is a major chemical constituent of T. chebula fruit showed potent activity. PURPOSE: This work was conducted to investigate the hepatoprotective activity and mechanisms of CA. METHODS: The hepatoprotective effect of CA was examined on hepatotoxic models of cells, zebrafish larvae and mice caused by tert-butyl hydrogen peroxide (t-BHP), acetaminophen (APAP) and CCl4, respectively. RESULTS: Pretreatment with CA could prevent t-BHP-induced damage in L-02 hepatocytes by blocking the production of ROS, reducing LDH levels and enhancing HO-1 and NQO1 expression via MAPK/Nrf2 signaling pathway. In animal experiments, CA significantly protected mice from CCl4-induced liver injury, as demonstrated by reduced ALT, AST and MDA levels, enhanced SOD activity, improved liver histopathological changes, and the activation of the Nrf2/HO-1 signaling pathway. CA metabolized to chebulic acid isomers with DPPH radical scavenging activity. In a transgenic zebrafish line with liver specific expression of DsRed RFP, CA diminished the hepatotoxicity induced by 10 mM APAP. CONCLUSION: Experiments in cell and two animal models demonstrated consistent results and comprehensively expounded the hepatoprotective effects of CA.

Inhibitory effects and molecular mechanisms of pentagalloyl glucose in combination with 5-FU on aggressive phenotypes of HepG2 cells.

This study examined the inhibition and mechanism of natural product pentagalloyl glucose (PGG) against HepG2 cells and determined the effects of its combination with the clinical chemotherapeutic drug, 5-FU. PGG was found to inhibit the proliferation, migration and invasion of HepG2 cells, induced G1 arrest and apoptosis in both concentration- and time- dependent manners. The combination of PGG and 5-FU had synergistic effects on reversal the aggressive phenotypes of HepG2 cells, increasing the proportion of Bax/Bcl-2, promoting the activation of caspase-9 and caspase-3, and inducing apoptosis. This combination upregulated P27 and cyclin B1, and downregulated cyclin E1, leading to G1 phase arrest. The combination significantly downregulated MDR1 and LRP1, suggesting the potential to reverse the resistance to 5-FU.

Cognitive magnetic resonance imaging-ultrasound fusion transperineal targeted biopsy combined with randomized biopsy in detection of prostate cancer.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers among men. Various strategies for targeted biopsy based on multiparametric magnetic resonance imaging (mp-MRI) have emerged, which may improve the accuracy of detecting clinically significant PCa in recent years. AIM: To investigate the diagnostic efficiency of a template for cognitive MRI-ultrasound fusion transperineal targeted plus randomized biopsy in detecting PCa. METHODS: Data from patients with an increasing prostate-specific antigen (PSA) level but less than 20 ng/mL and at least one lesion suspicious for PCa on MRI from December 2015 to June 2018 were retrospectively analyzed. All patients underwent cognitive fusion transperineal template-guided targeted biopsy followed by randomized biopsy outside the targeted area. A total of 127 patients with complete data were included in the final analysis. A multivariable logistic regression analysis was conducted, and a two-sided P < 0.05 was considered statistically significant. RESULTS: PCa was detected in 66 of 127 patients, and 56 cases presented clinically significant PCa. Cognitive fusion targeted biopsy alone detected 59/127 cases of PCa, specifically 52/59 cases with clinically significant PCa and 7/59 cases with clinically insignificant PCa. A randomized biopsy detected seven cases of PCa negative on targeted biopsy, and four cases had clinically significant PCa. PSA density (OR: 1.008, 95%CI: 1.003-1.012, P = 0.001; OR: 1.006, 95%CI: 1.002-1.010, P = 0.004) and Prostate Imaging-Reporting and Data System (PI-RADS) scores (both P < 0.001) were independently associated with the results of cognitive fusion targeted biopsy combined with randomized biopsy and targeted biopsy alone. CONCLUSION: This single-centered study proposed a feasible template for cognitive MRI-ultrasound fusion transperineal targeted plus randomized biopsy. Patients with higher PSAD and PI-RADS scores were more likely to be diagnosed with PCa.

The impact of atrial fibrillation on outcomes in patients undergoing radical prostatectomy.

PURPOSE: To assess the role of atrial fibrillation (AF) on complicating inpatient outcomes of radical prostatectomy (RP). MATERIALS AND METHODS: We identified patients treated with RP during 2012-2014 within National Inpatient Sample (NIS) database. Length of stay, cost of hospitalization, and in-hospital complications were compared between patients with or without diagnosis of AF. Propensity score matching methods and multivariable regression analysis were used to adjust for potential confounders and a trend analysis was conducted. RESULTS: Patients with AF had a significantly longer hospital stay (coefficient 0.19, 95% CI 0.09-0.29, P < 0.001) and higher cost (coefficient 0.10, 95% CI 0.06-0.15, P < 0.001). Post-operative cardiac complications were significantly higher for patients with AF (OR 16.38, 95% CI 7.72-34.74, P < 0.001), while no differences were found in other complications between the two groups. Similar results were shown in propensity score matching methods. The cardiac complications after laparoscopic RP (OR: 37.71, 95% CI 1.85-768.73, P = 0.018) and open RP (OR: 16.78, 95% CI 1.41-199.51, P = 0.026) were significantly higher than robot-assisted RP (RARP) in patients with AF. The results of trend study indicated that postoperative cardiac complication rates showed a trend of decreasing year by year while the prevalence of AF was rising. CONCLUSIONS: Perioperative AF is associated with increased cardiac complications, longer hospital stay and higher cost in PCa patients undergoing RP. RARP may be a preferred choice for patients with AF. Attention should be paid to this special patient population. Reasonable pre-operative risk stratification and standardized management should be done to decrease perioperative complications.

Oncological impact of different distal ureter managements during radical nephroureterectomy for primary upper urinary tract urothelial carcinoma.

BACKGROUND: The current standard surgical treatment for non-metastatic upper urinary tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU) with bladder cuff excision (BCE). Typically, BCE techniques are classified in one of the following three categories: An open technique described as intrasvesical incision of the bladder cuff, a transurethral incision of the bladder cuff (TUBC), and an extravesical incision of the bladder cuff (EVBC) method. Even though each of these management techniques are widely used, there is no consensus about which surgical intervention is superior, with the best oncologic outcomes. AIM: To investigate the oncological outcomes of three BCE methods during RNU for primary UTUC patients. METHODS: We retrospectively analyzed the data of 248 primary UTUC patients, who underwent RNU with BCE between January 2004 to December 2018. Patients were analyzed according to each BCE method. Data extracted included patient demographics, perioperative parameters, and oncological outcomes. Statistical analyses were performed using chi-square and log-rank tests. The Cox proportional hazards regression model was utilized to identify independent predictors. P < 0.05 was considered statistically significant. RESULTS: Of the 248 participants, 39.9% (n = 99) underwent intrasvesical incision of the bladder cuff, 38.7% (n = 96) EVBC, and 21.4% (n = 53) TUBC. At a median follow-up of 44.2 mo, bladder recurrence developed in 17.2%, 12.5%, and 13.2% of the cases, respectively. Cancer-specific deaths occurred in 11.1%, 5.2%, and 7.5% of patients, respectively. Kaplan-Meier survival curves with a log-rank test highlighted no significant differences in intravesical recurrence-free survival, cancer-specific survival, and overall survival among these approaches with P values of 0.987, 0.825, and 0.497, respectively. Multivariate analysis showed that the lower ureter location appears to have inferior intravesical recurrence-free survival (P = 0.042). However, cancer-specific survival and overall survival were independently influenced by tumor stage (hazard ratio [HR] = 8.439; 95% confidence interval: 2.424-29.377; P = 0.001) and lymph node status (HR = 14.343; 95%CI: 5.176-39.745; P < 0.001). CONCLUSION: All three techniques had comparable outcomes; although, EVBC and TUBC are minimally invasive. While based upon rather limited data, these findings will support urologists in blending experience with evidence to inform patient choices. However, larger, rigorously designed, multicenter studies with long term outcomes are still required.

Comparing the Oncological Outcomes of Cryoablation vs. Radical Prostatectomy in Low-Intermediate Risk Localized Prostate Cancer.

Purpose: To compare the oncologic outcomes of cryoablation (CA) and radical prostatectomy (RP) in patients with low- and intermediate-risk localized prostate cancer (PCa). Materials and Methods: PCa patients who received CA or RP between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Multivariable Cox proportional hazard analysis was used to compare the prostate cancer-specific survival (CSS) and overall survival (OS). We conducted 1:3 propensity score matching and adjusted standardized mortality ratio weighting (SMRW) to balance the clinicopathological characteristics. Results: Ninety-seven thousand seven hundred eighty-three patients were identified after preliminary screening. After matching, the CA and RP groups included 1,942 and 5,826 patients and had median follow-up periods of 85 and 72 months, respectively. CA had lower CSS and OS rates (hazard ratio [HR], 2.07; P = 0.007; HR, 2.09; P < 0.001, respectively) than did RP, which was consistent in the SMRW model (CSM: HR, 2.66; P < 0.001; OS: HR, 2.29; P < 0.001). The 10-years CSS and OS for CA vs. RP were 98.1 vs. 99.2% and 61.3 vs. 79.9%, respectively. Conclusions: In patients with low- to intermediate-risk localized PCa, CA had lower CSS rates than did RP. However, the high 10-years CSS rates indicated that CA could be an option for those who are not RP candidates. Further high-quality trials are needed to confirm and expand our findings.

Positive node burden rather than the number of removed nodes impacts survival in patients with node-positive prostate cancer.

BACKGROUND: The value of pelvic lymphadenectomy during radical prostatectomy (RP) remains controversial. This study aims to test the effects of the number of removed lymph nodes (RLN), positive nodes (pLN), and pLN ratio (pLNR) on cancer-specific survival (CSS) in patients with node-positive prostate cancer (PCa). METHODS: A total of 2458 patients with a greater than 5% probability of lymph node invasion according to the updated Briganti nomogram who harboured pathologically confirmed positive nodes in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were identified. Multivariable Cox regression with forward stepwise selection was performed to identify independent risk factors for CSS. Maximally selected rank statistics were used to determine the most informative cut-off value for pLN and pLNR. RESULTS: The median pLN counts and RLN in the study were two (interquartile range [IQR] 1- 3) and 18 (IQR 15-23), respectively. The RLN counts could not predict CSS, while the higher pLN and pLNR were associated with worse CSS (hazard ratio [HR], 1.11; p < 0.001 and HR, 1.01; p < 0.001, respectively). Patients with ≤ 2 pLN or pLNR ≤ 20% had significantly better CSS than those with pLN > 2 or pLNR > 20% (HR, 1.38 (1.08-1.77); p = 0.009; HR, 1.77 (1.41-2.22); p < 0.001, respectively). CONCLUSIONS: In patients with node-positive PCa, pelvic lymphadenectomy provides important information for staging, prognosis, and guiding after RP therapy; however, it does not play a therapeutic role. The pLN counts and pLNR were independent predictors of CSS.

Clinical outcomes of sacral neuromodulation in non-neurogenic, non-obstructive dysuria: A 5-year retrospective, multicentre study in China.

BACKGROUND: Management of non-neurogenic, non-obstructive dysuria represents one of the most challenging dilemmas in urological practice. The main clinical symptom is the increase in residual urine. Voiding dysfunction is the main cause of dysuria or urinary retention, mainly due to the decrease in bladder contraction (the decrease in contraction amplitude or duration) or the increase in outflow tract resistance. Sacral neuromodulation (SNM) has been used for > 10 years to treat many kinds of lower urinary tract dysfunction. It has become increasingly popular in China in recent years. Consequently, studies focusing on non-neurogenic, non-obstructive dysuria patients treated by SNM are highly desirable. AIM: To assess the outcome of two-stage SNM in non-neurogenic, non-obstructive dysuria. METHODS: Clinical data of 54 patients (26 men, 28 women) with non-neurogenic, non-obstructive dysuria treated by SNM from January 2012 to December 2016 in ten medical centers in China were retrospectively analyzed. All patients received two or more conservative treatments. The voiding diary, urgency score, and quality of life score before operation, after implantation of tined lead in stage I (test period), and during short-term follow-up (latest follow-up) after implantation of the implanted pulse generator in stage II were compared to observe symptom improvements. RESULTS: Among the 54 study patients, eight refused to implant an implanted pulse generator because of the unsatisfactory effect, and 46 chose to embed the implanted pulse generator at the end of stage I. The conversion rate of stage I to stage II was 85.2%. The average follow-up time was 18.6 mo. There were significant differences between baseline (before stage I) and the test period (after stage I) in residual urine, voiding frequency, average voiding amount, maximum voiding amount, nocturia, urgency score, and quality of life score. The residual urine and urgency score between the test period and the latest follow-up time (after stage II) were also significantly different. No significant differences were observed for other parameters. No wound infection, electrode breakage, or other irreversible adverse events occurred. CONCLUSION: SNM is effective for patients with non-neurogenic, non-obstructive dysuria showing a poor response to traditional treatment. The duration of continuous stimulation may be positively correlated with the improvement of residual urine.

The sphingosine-1-phosphate/RhoA/Rho associated kinases/myosin light chain pathway in detrusor of female rats is down-regulated in response to ovariectomy.

BACKGROUND: Dysuria is one of the main symptoms of genitourinary syndrome of menopause, which causes serious disruption to the normal life of peri-menopausal women. Studies have shown that it is related to decrease of detrusor contractile function, but the exact mechanism is still poorly understood. Previous results have suggested that the sphingosine-1-phosphate (S1P) pathway can regulate detrusor contraction, and this pathway is affected by estrogen in various tissues. However, how estrogen affects this pathway in the detrusor has not been investigated. In this study, we detected changes of the S1P/RhoA/Rho associated kinases (ROCK)/myosin light chain (MLC) pathway in the detrusor of ovariectomized rats in order to explore the underlying mechanism of dysuria during peri-menopause. METHODS: Thirty-six female Sprague-Dawley rats were randomly divided into SHAM (sham operation), OVX (ovariectomy), and E groups (ovariectomy + estrogen), with 12 rats in each group. We obtained bladder detrusor tissues from each group and examined the mRNA and protein levels of the major components of the S1P/RhoA/ROCK/MLC pathway using quantitative real-time polymerase chain reaction and Western blotting, respectively. We also quantified the content of S1P in the detrusor using an enzyme linked immunosorbent assay. Finally, we compared results between the groups with one-way analysis of variance. RESULTS: The components of the S1P pathway and the RhoA/ROCK/MLC pathway of the OVX group were significantly decreased, as compared with SHAM group. The percent decreases of the components in the S1P pathway were as follows: sphingosine kinase 1 (mRNA: 39%, protein: 45%) (both P < 0.05), S1P (21.73 ±â€Š1.09 nmol/g vs. 18.86 ±â€Š0.69 nmol/g) (P < 0.05), and S1P receptor 2/3 (S1PR2/3) (mRNA: 25%, 27%, respectively) (P < 0.05). However, the protein expression levels of S1PR2/3 and the protein and mRNA levels of SphK2 and S1PR1 did not show significant differences between groups (P > 0.05). The percent decreases of the components in the RhoA/ROCK/MLC pathway were as follows: ROCK2 (protein: 41%, mRNA: 36%) (both P < 0.05), p-MYPT1 (protein: 54%) (P < 0.05), and p-MLC20 (protein: 47%) (P < 0.05), but there were no significant differences in the mRNA and protein levels of RhoA, ROCK1, MYPT1, and MLC20 (all P > 0.05). In addition, all of the above-mentioned decreases could be reversed after estrogen supplementation (E group vs. SHAM group) (all P > 0.05). CONCLUSION: In this study, we confirmed that ovariectomy is closely associated with the down-regulation of the S1P/RhoA/ROCK/MLC pathway in the rat detrusor, which may be one mechanism of dysuria caused by decreased contractile function of the female detrusor during peri-menopause.

Rare primary lymphoepithelioma-like carcinoma of the renal pelvis.

Lymphoepithelioma-like carcinoma (LELC) is a rare, malignant epithelial tumour which can arise within the upper urinary tract. This letter adds to a previous systematic review and cumulative analysis of 28 published upper urinary tract-LELC cases which provided insight into this disease; however, the current evidence does not provide clinicians with clear guidelines due to its rarity. Therefore, the aim was to report a new case of renal pelvis LELC presented in our hospital. In this instance, we were able to report treatment experience and long-term follow-up results. This patient presented with hypertension and haemturia which initiated further investigation. While ultrasound identified an hypechoic mass, no malignant cells were detected using cytological testing. Abdominal magnetic resonance imaging identified a slightly enhanced mass in the left renal pelvis with no evidence of lymph node metastasis. Ureteroscopic tumor biopsy suggested the existence of urothelial carcinoma, hence, laparoscopic radical left nephroureterectomy with bladder cuff excision was performed. Through patient-practitioner consultations, we decided to adopt a "watch and wait" approach after radical nephroureterectomy rather than administering chemotherapy. Although, we would encourage clinicians to record and publish cases to garner insight into this type of malignant disease.

The prevalence of urinary incontinence in men and women aged 40 years or over in China, Taiwan and South Korea: A cross-sectional, prevalence-based study.

OBJECTIVES: To assess prevalence of urinary incontinence (UI), including urgency UI (UUI), stress UI (SUI) and mixed UI (MUI) in individuals aged ≥40 years in China, Taiwan and South Korea. METHOD: This was a post hoc analysis of a cross-sectional, questionnaire-based internet survey. Participants were asked questions relating to urinary symptoms, health-related quality of life (HRQoL) and mental health (using the HRQoL 12-item short form health survey mental health and physical domains, and the Hospital Anxiety and Depression Scale), visits to healthcare professionals (HCPs) for any reason or for urinary symptoms, treatments for urinary symptoms and treatment satisfaction. RESULTS: Of 8284 survey participants, 1818 (22%) reported any UI (men 17.3%, women 26.4%). MUI was the most prevalent (overall 9.7%, men 6.8%, women 12.6%) followed by SUI (overall 7.9%, men 5.1%, women 10.7%) and UUI (overall 4.3%, men 5.5%, women 3.2%). HRQoL, anxiety and depression scores were poor in all participants with UI; MUI was associated with the worst scores. Of the participants with UI, 46.9% visited HCPs for urinary symptoms (highest proportion [62.7%] among participants with MUI). Approximately 80% of participants with UI followed treatment, with prescribed medicine being the most common form (38.1%). Over half of participants (59.6%) were somewhat, very, or extremely satisfied with their treatment. MUI was associated with least satisfaction. CONCLUSION: UI was associated with substantial problems, including an adverse impact on HRQoL. Medication failed to satisfy many individuals with UI. Efforts to educate the public and physicians about the impact of UI could improve diagnosis and treatment rates.

Lymphoepithelioma-like carcinoma of the upper urinary tract: A systematic review of case reports.

BACKGROUND: Lymphoepithelioma-like carcinomas (LELCs) are rare, malignant epithelial tumors, generally considered a subtype of squamous cell carcinoma. LELCs are undifferentiated and can occur in multiple tissues, although LELCs in the urinary tract are extremely rare. As such, evidence does not provide clinicians with guidelines for the best practices. Even though this is a rare disease, it is associated with high morbidity and mortality. Therefore, we must learn to differentiate LELC types and identify risk factors for early identification. AIM: To develop an evidence base to guide clinicians treating primary LELCs of the upper urinary tract (UUT-LELC). METHODS: We performed a systematic review of all reports on UUT-LELC from the first published case in 1998 until October 2019, according to the PRISMA. A database was then developed by extracting data from previously published reports in order to analyze interactions between clinical characteristics, pathological features, interventions and outcomes. Survival was analyzed using Kaplan-Meier estimates, which were compared using log rank tests. RESULTS: A total of 28 previously published cases were identified for inclusion. The median age was 72 years with a male to female ratio of 4:3. Pure type LELCs were most common with 48.3% (n = 14), followed by 37.9% (n = 11) predominant LELCs and 3.4% (n = 1) focal LELCs. Epstein-Barr virus testing was negative in all cases. Fourteen patients received radical nephroureterectomy (RNU)-based intervention. Twenty-three patients survived with no evidence of further metastasis, although six died before the median 18 mo follow-up point. Survival analysis suggests pure histological subtypes, and patients who receive complete tumor resection have more favorable prognoses. As always in cancer care, early identification generally increases the probability of interventional success. CONCLUSION: The most effective treatment for UUT-LELC is RNU-based therapy. Since cases are few in number, case reporting must be enhanced and publishing encouraged to both save and prolong lives.