OBJECTIVES:To establish a novel spinal cord hemisection-induced neurogenic bladder (SCHNB) rat model combined with sacral neuromodulation (SNM) and evaluate the immediate effects of SNM on bladder function and morphology in SCHNB. MATERIALS AND METHODS:Female Sprague-Dawley rats were randomly assigned to three groups: control, SCHNB, and SCHNB + SNM groups. Rats in control group underwent only T9-T10 laminectomy, SCHNB group received right T9-T10 spinal cord hemisection and electrode implantation without electrical stimulation, SCHNB + SNM group underwent the same procedure as SCHNB group but also received daily 3-hours SNM beginning on postoperative day 1 for 3 weeks. All rats subsequently underwent motor function assessment, bladder ultrasonography and cystography, cystometric testing, and histological analysis of spinal cord and bladder tissues. RESULTS:Ultrasonography revealed significantly increased post void residual in SCHNB group compared to control and SCHNB + SNM groups. Bladder weight in SCHNB group was significantly higher than in control and SCHNB + SNM groups. Cystometric analysis showed a shorter voiding contraction interval in SCHNB + SNM group than control group but longer than SCHNB group. During bladder filling, SCHNB group exhibited multiple uninhibited detrusor contractions, SCHNB + SNM group showed fewer uninhibited contractions and a lower maximum pressure. Histological examination revealed that compared to control and SCHNB + SNM groups, SCHNB group displayed disorganized bladder mucosal epithelium, disrupted and loosened lamina propria, tissue edema, and increased fibrosis. CONCLUSIONS:This model of SCHNB combined with SNM provides a new experimental platform for SNM research. Immediate SNM effectively inhibited bladder overactivity and partially improved functional and structural abnormalities of the bladder.
Bladder outlet obstruction (BOO) induces urinary bladder wall remodeling. However, the function of exosomal miRNAs from bladder smooth muscle cells (BSMCs) in BOO development remains unclear. Differentially expressed miRNA profiles in BSMC-derived exosomes from BOO rat models and normal rats were analyzed using miRNA sequencing. LPS-induced BSMCs were treated with exosomes from BOO-extracted BSMCs. The uptake of exosomes in BSMCs was assessed by PKH26 fuorescent dye. The protein levels of MCP-1, IL-1β, TNF-α, α-SMA, and collagen I were detected by western blotting and qPCR analysis. Cell proliferation and apoptosis were assessed by CCK-8, EdU, and flow cytometry, respectively. The interaction between miR-200b-3p and zonula occludens-1 (ZO-1) 3’UTR was analyzed by luciferase reporter gene assay. Results indicated that miRNA-200b-3p was upregulated in BSMC-derived exosomes from BOO rats compared with the sham group. Treatment with exosomes from BOO-extracted BSMCs further aggravated LPS-induced BSMC proliferation, inflammation, and fibrosis. Inhibition of miR-200b-3p attenuated these effects, which were restored by silencing ZO-1 expression in BSMCs. We identified upregulation of exosomal miR-200b-3p from BSMCs in BOO rats and demonstrated that BSMC-derived exosomes enhanced proliferation, inflammation, and fibrosis of BSMCs via miR-200b-3p/ZO-1 axis. Our work identifies a potential target for diagnosis and therapy in BOO.
Table S2 shows the clinical information of patients from Qilu Hospital of Shandong University.
Introduction Overactive bladder (OAB) in children is clinically common and seriously affects the physical and mental health of children. The voiding frequency (VF) is an important basis for the diagnosis of OAB. The emergence of home-uroflowmetry (HUF) has allowed the patients to record the VF while recording the uroflowmetry at home, and the voiding at home can show the real voiding situation. However, the use of HUF to assess OAB in children and its clinical significance has not been reported in the literature. Thus, this study investigate the value of HUF in evaluation of voiding function in children with OAB and survey the VF of healthy children in Mainland China. Materials and methods From May 2021 to July 2023, 52 children with OAB aged 7-10 years, 48 age-matched volunteers (control group) accepted HUF. Daytime VF and nighttime VF, voided volume (VV) per time, 24-h voided volume (24h-VV), maximum flow rate (Qmax), voiding time (VT), and uroflow pattern were recorded and compute corrected maximum urine flow rate (cQmax). VF in 600 health pupils (7-10 years) from five primary schools in Henan Province China were selected for questionnaire survey by cross-sectional survey and multi-stage sampling methods. Results 52 children with OAB and 48 healthy children completed the available 48-h HUF recordings. 24-hour, daytime, and nighttime VF, and cQmax were higher in the OAB group than in the control group (P < 0.05). However, average VV, Qmax, and VT were lower in the OAB group than in the control group (P < 0.05). There was no significant difference in 24h-VV between two groups (P > 0.05). A total of 502 questionnaires qualified for statistical analysis, and the 24h-VF was 6.3 +/- 0.95 times, daytime VF was 5.6 +/- 0.89 times, and nighttime VF was 0.7 +/- 0.59 times. There was no significant difference in the comparison of 24-h, daytime, and nighttime VF between boys and girls and in the comparison of VF by age (P > 0.05). Compared with the results of the questionnaire, the difference of VF in HUF control group was not statistically significant (P > 0.05). Conclusions The VF in children is similar to that of adults and the HUF is a useful tool with the ability to more realistically record changes in voiding function in children with OAB.
ABSTRACT Purpose: Currently, detethering surgery (DS) is the modality most extensively utilized to treat primary tethered cord syndrome (TCS). Disappointingly, some children without bladder impairment showed a deterioration of bladder function after surgery, which critically influences the health-related quality of life. It was hypothesized that the DS might have a significant effect on bladder function and psychology. Therefore, the purpose of this study was to investigate the effect of DS on bladder function and quality of life in children with primary TCS. Materials and Methods: A retrospective study of 83 patients aged 6 to 10 years who were diagnosed with TCS and underwent DS between 2022 and 2023. The urodynamic parameters and score, psychological-behavioral profile, and lower urinary tract symptoms were compared before and after DS. Additionally, the patients were divided into the normal group and the abnormal group according to the preoperative urodynamics parameters. Results: A total of 66 children fulfilled the criteria, with a mean age at surgery of 89.5 ± 13.7 months. There were statistically significant differences in bladder detrusor sphincter synergy and urodynamic score and no statistically significant difference in the remaining urodynamic parameters and psychological-behavioral items before and after DS. The proportion of bladder dysfunction that improved or did not worsen after surgery was higher in the Abnormal group than in the Normal group. Nevertheless, the detection rate of each psychological behavior abnormality in children with TCS was higher compared with that of normal children, both preoperatively and postoperatively. Conclusions: DS could not considerably ameliorate pre-existing bladder dysfunction and patients exhibiting non-progressive bladder dysfunction could be treated conservatively with close observation. TCS plagues patients all the time even if detethering. Psychological counseling for children with TCS should be strengthened after DS.
Uroflowmetry is an uroflow measurement technique used to record the voided volume (VV) and flow rate, which can help clinicians objectively evaluate lower urinary tract function. Currently, few uroflowmetry studies have focused on the female population,[1] especially on the uroflow curve standard analysis. Hence, we sought to establish dependable uroflow reference values and nomograms for Chinese women and to evaluate the relationship between uroflow patterns and demographic data. This multicenter survey was conducted between July 2020 and April 2023. Female participants aged 18 years or above were recruited from 11 cities [Supplementary Table 1, https://links.lww.com/CM9/B973] through different modes, such as Internet advertising, social networks, and clinics. Volunteers who were diagnosed with cognitive impairment, urinary incontinence, and individuals with overactive bladder symptom score (OABSS) ≥3, history of lower urinary tract surgery were excluded from the study. This study was conducted in accordance with the principles of the Declaration of Helsinki and all individuals provided informed consent to participate in this study. Ethical approval was obtained from the Beijing Hospital Ethics Committee (No. 2020BJYYEC-085-02). The electronic questionnaire consisted of three parts: a demographic information sheet (Part 1), the Chinese version of the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF, Part 2), and the OABSS (Part 3). A home-based uroflowmetry (HBU) system was distributed after the completion of an electronic questionnaire [Supplementary Figure 1, https://links.lww.com/CM9/B973]. Each uroflow curve met the following quality criteria: VV ≥125 mL. Each participant was required to perform ≥3 qualified uroflowmetry tests. To standardize the classification of uroflow patterns, five categories were defined: (1) Fluctuating type (with at least two fluctuations in the curve and amplitude in each wave >1/5 of the maximum value); (2) Prolonged type (time to peak >15 s); (3) Intermittent type (with an interruption number ≥1, and the adjacent uroflow peaks of interruption >3 mL/s); (4) Plateau type (A point = the first point that reaches 70% of the maximum value, B point = the last point that reaches 70% of the maximum value, and slope of the fitted line between A point and B point >–0.7); 5. Bell-shaped (one peak, change before and after the peak less than 1/3 of the flow time, and no other curve-type features). The HBU (Xiaoyu, Cliapath-RJ01, Guangzhou, China) was sent to the National Center of Metrology (Guangzhou; Certificate No. LZT202102176) for testing. With a measured error of 0.1 g, the HBU can provide accurate measurements at 0–1000 mL volumes and maximum flow rates of 0–100 mL/s. The definitions are shown in the Supplementary File 1, https://links.lww.com/CM9/B973. Continuous variables were expressed as mean (interquartile range [IQR]). The Kruskal–Wallis H test was used for comparison among groups. Bivariate correlations were tested using the Spearman's rho and linear regression analysis was used for multivariate analysis. Statistical significance was set at P ≤0.05. Data were analyzed using SPSS statistical software (version 22.0; SPSS Inc., Chicago, IL, USA) and R software (version 3.6.3; The R Project for Statistical Computing, Vienna, Austria). Of the 2461 volunteers enrolled in this study, 406 were excluded (282 volunteers were aged <18 years/lower urinary tract symptoms [LUTS]-related oral medications/LUTS-related surgery history, 124 did not meet the uroflow qualified criteria). A total of 8439 uroflows were collected from 2055 volunteers, and 1994 uroflow data were excluded. The demographic table and uroflowmetry parameters of the age groups are shown in the Supplementary Tables 2-5, https://links.lww.com/CM9/B973. The ages of the volunteers ranged from 18 years old to 93 years old, with an average age of 51.4 ± 17.4 years. Uroflow parameters of the general group were as follows: VV 275.1 ± 104.3 mL, flow time 21.1 ± 9.3 s, Qave 14.0 ± 5.8 mL/s, Qmax 24.8 ± 9.4 mL/s, and time to peak 5.4 ± 3.2 s; uroflow parameter of the aged group were as follows: VV 276.4 ± 104.8 mL, flow time 23.0 ± 10.1 s, Qave 13.1 ± 5.7 mL/s, Qmax 23.5 ± 9.3 mL/s, and time to peak 5.3 ± 2.9 s. Aged women were divided into three groups (60–69 years, 70–79 years, and over 80 years). A comparison of different age groups revealed a significant decrease in flow rate among individuals aged 60 years and above ([Qmax & Qave] P <0.001). After eliminating the voiding volume influence, the correlation between age and corrected Qmax remained steady (cc = –0.18, P <0.001). In the aged groups, the downward trend of the flow rate was more apparent in the 80+ year group (Supplementary Figure 2, https://links.lww.com/CM9/B973, P <0.001). BSA, BMI, Eutocia, and macrosomia showed weak correlations with Qmax (P <0.001). The variable most impacting the flow rate was VV in both univariate and multivariate analyses, which can be described by a quadratic equation [Figure 1]. The equations in general and aged groups are shown in Supplementary File 2, https://links.lww.com/CM9/B973.Figure 1: Flow–volume nomograms: (A) Q max with VV in the general group, (B) Q ave with VV in the general group, (C) Q max with VV in the young age group, (D) Q ave with VV in the young age group, (E) Q max with VV in the aged group, (F) Q ave with VV in the aged group. Percentage values represent confidence limits. M = mean line. 68% and 95% confidence intervals were adopted to construct the flow–volume nomograms. VV: Voided volume.In the analysis of 8433 urinary flow rate records (6 records were deleted because they could not be classified into the five categories), the distribution of uroflow patterns was as follows: 4106 bell types, 2571 fluctuating types, 722 plateau types, 535 prolonged types, and 499 intermittent types. Among participants with bell-shaped urinary flow, 86.3%(3543/4106) rated their Quality of Life (QoL) as either satisfied or very satisfied. However, this percentage decreased to 78.3% (419/535) in the prolonged type. Similar trends were observed in the urination scores, with 73.1% (3001/4106) of those with a bell-shaped flow expressing satisfaction (urination score = 5), whereas the other categories remained below 70% (the satisfaction rates were 1743/2571 for fluctuating type, 311/499 for intermittent type, 464/722 for plateau type, and 314/535 for prolong type). With advancing age, the proportion of bell-type individuals decreased from 53.7% (737/1372) in the 18–29 years age group to 36.1% (65/180) in the >80 years age group (P <0.001). Correspondingly, only 1.9% (78/4106) of bell-type subjects were at risk of sarcopenia, while the prolonged type had 6.9% (37/535) of subjects with sarcopenia risk (P <0.001). Additionally, the prevalence of the bell type was influenced by parity (P = 0.004); 52.4% (840/1602) of nulliparous subjects exhibited a bell-shaped uroflow pattern, whereas in those with three or more childbirths, only 46.9% (450/960) displayed bell-shaped uroflows. Slight differences in BMI and BSA were observed between the different uroflow patterns (P = 0.012 and P = 0.002, respectively). Overall, individuals with predominantly bell-type patterns appeared to have a higher QoL. No significant correlations were identified between smoking, alcohol consumption, educational history, age at first childbirth, and uroflow patterns (P >0.05). With limited research on the elderly female population and uroflow patterns, this multicenter study aimed to provide normal uroflowmetry parameters and analyze the factors influencing uroflow patterns. In this study, we set VV >125 mL and more than three flows within 48 h as the qualifying standard for better simulation of daily urination patterns. The HBU test provides a private and familiar environment that eliminates psychological and environmental influences on subjects.[2,3] Multivariate analysis revealed that age, VV, BMI, and eutocia were associated with the uroflow rate [Supplementary Table 3, https://links.lww.com/CM9/B973]. The correlation between age and uroflow rate remains controversial in current studies, but most studies have reached a consensus that uroflow decreases with age. The positive correlation between BMI and Qmax may be because obese patients often have significantly higher baseline intra-abdominal pressure; similar results were found in another study.[1] Several female uroflow nomograms have been established.[1,4] Haylen et al[4] enrolled 249 female volunteers aged 16–63 years to construct Liverpool nomograms, with the advantage of accommodating a wide range of VVs but limited recruitment in the aged population. In this study, we established a nomogram for the elderly population to fill this gap. Currently, there is no consensus on the standard methodology for uroflow patterns. Although a few studies have established a relatively standard analytical approach, the majority depend on subjective classifications by researchers, thereby raising concerns about credibility. Notably, few researches have analyzed uroflow patterns in the normal population. In this study, we identified a correlation between uroflow patterns and demographic data. These findings laid the groundwork for subsequent in-depth investigations. This study had several limitations. First, patients with LUTS were not included in our study to validate the nomogram, and we plan to enroll more patients with LUTS to validate our nomogram next year. Second, to include a diverse range of ages and regions, the PVR of each volunteer was not recorded; instead, all patients with LUTS were excluded. The strengths of this study include the large sample size of aged volunteers, repetitive measurements, and standard uroflow pattern analysis. This largest female uroflowmetry study provides valuable insights into female uroflow in China. In conclusion, this multicenter study established a flow–volume nomogram and provided uroflow parameters for different age groups; we further evaluated the relationship between uroflow patterns and demographic data. Based on these findings, Qave <10 mL/s in the aged group should not be directly labeled as abnormal, warranting caution in the diagnosis. Bell-type uroflow may reflect a better QoL. Funding This work was supported by a grant of National Key Program (No. 2018YFC2002202). Conflicts of interest None. Registration number Chinese Clinical Trial Registry, No. ChiCTR2100054334.
ObjectivesSacral neuromodulation is an effective, minimally invasive treatment for refractory lower urinary tract dysfunction. However, regular postoperative programming is crucial for the maintenance of the curative effects of electronic sacral stimulator devices. The outbreak of coronavirus disease 2019 (COVID-19) limited the ability of practitioners to perform traditional face-to-face programming of these stimulators. Therefore, this study aimed to evaluate the application of remote programming technology for sacral neuromodulation during the COVID-19 pandemic in China. Materials and methodsWe retrospectively collected data including baseline and programming information of all patients with lower urinary tract dysfunction who underwent sacral neuromodulation remote programming in China after the outbreak of COVID-19 (i.e., December 2019). The patients also completed a self-designed telephone questionnaire on the subject. ResultsA total of 51 patients from 16 centers were included. They underwent 180 total remote programming visits, and 118, 2, 25, and 54 voltage, current, pulse width, and frequency adjustments, respectively, were performed. Additionally, remote switching on and off was performed 8 times; impedance test, 54 times; and stimulation contact replacement, 25 times. The demand for remote programming was the highest during the first 6 months of sacral neuromodulation (average, 2.39 times per person). In total, 36 out of the 51 patients completed the questionnaire survey. Of these, all indicated that they chose remote programming to minimize unnecessary travel because they had been affected by COVID-19. The questionnaire also showed that remote programming could reduce the number of patient visits to the hospital, save time, reduce financial costs, and would be easy for patients to master. All surveyed patients indicated that they were satisfied with remote programming and were willing to recommend it to other patients. ConclusionRemote programming for sacral neuromodulation is feasible, effective, safe, and highly recommended by patients with refractory lower urinary tract dysfunction. Remote programming technology has great development and application potential in the post-pandemic era.
Bladder outlet obstruction (BOO) is a common disease that always make the bladder develops from inflammation to fibrosis. This study was to investigate the effect of exosomes from human urine-derived stem cells (hUSCs) on bladder fibrosis after BOO and the underlying mechanism. The BOO mouse model was established by inserting a transurethral catheter, ligation of periurethral wire, and removal of the catheter. Mouse primary bladder smooth muscle cells (BSMCs) were isolated and treated with TGFβ1 to mimic the bladder fibrosis model in vitro. Exosomes from hUSCs (hUSC-Exos) were injected into the bladder of BOO mice and added into the culture of TGFβ1-induced BSMCs. The associated factors in mouse bladder tissues and BSMCs were detected. It was confirmed that the treatment of hUSC-Exos alleviated mouse bladder fibrosis and down-regulated fibrotic markers (a-SMA and collagen III) in bladder tissues and TGFβ1-induced BSMCs. Overexpression of NRF1 in hUSC-Exos further improved the effects of hUSC-Exos on bladder fibrosis both in vivo and in vitro. TGFβR1 was a target of NRF1 and miR-301b-3p, and miR-301b-3p was a target of NRF1. It was next characterized that hUSC-Exos carried NRF1 to up-regulate miR-301B-3p, thereby reducing TGFβR1level. Our results illustrated that hUSC-Exos carried NRF1 to alleviate bladder fibrosis through regulating miR-301b-3p/TGFβR1 pathway.
The effects of circular RNAs (circRNAs) on bladder outlet obstruction (BOO)-induced hypertrophy and fibrogenesis in rats and hypoxia-induced bladder smooth muscle cell (BSMC) fibrosis remain unclear. This study aimed to determine the regulatory role of circRNAs in the phenotypic changes in BSMCs in BOO-induced rats.circRNAmicroarray and real-time PCR were used to explore differentiated expressed circRNAs. Bioinformatics analyses and dual-luciferase reporter were performed to identify the targets for circRNA PVT1 (circPVT1). BOO was performed to establish a bladder fibrosis animal model. The circPVT1 and suppressor of cytokine signaling 3 (SOCS3) expression levels were upregulated (p = 0.0061 and 0.0328, respectively), whereas the microRNA-203a (miR-203) level was downregulated in rats with bladder remodeling (p=0.0085). Bioinformatics analyses and dual-luciferase reporter assay results confirmed that circPVT1 sponges miR-203 and that the latter targets the 3′-untranslated region of SOCS3. Additionally, circPVT1 knockdown alleviated BOO-induced bladder hypertrophy and fibrogenesis. Furthermore, hypoxia was induced in BSMCs to establish a cell model of bladder fibrosis. Hypoxia induction in BSMCs resulted in upregulated circPVT1 and SOCS3 levels (p = 0.0052) and downregulated miR-203 levels. Transfection with circPVT1 and SOCS3 shRNA ameliorated hypoxia-induced transforming growth factor-β (TGF-β1), TGFβR1, α-smooth muscle actin, fibrotic growth factor, extracellular matrix subtypes, BSMC proliferation, and apoptosis-associated cell injury, whereas co-transfection with miR-203 inhibitor counteracted the effect of circPVT1 shRNA on these phenotypes.These findings revealed a novel circRNA regulator of BOO-associated bladder wall remodeling and hypoxia-induced phenotypic changes in BMSCs by targeting the miR-203–SOCS3 signaling axis.
To determine the prevalence of bladder and bowel dysfunction (BBD) and its relationship with delayed elimination communication (EC) in children. A cross-sectional study was carried out in kindergartens and primary schools in mainland China. A total of 10,166 children ranging from 4 to 10 years old were included. A total of 10,166 valid questionnaires were collected, and 409 children were diagnosed with BBD. The overall prevalence was 4.02% (409/10,166) and decreased with age, from 6.19% at age 4 to 1.96% at age 10. With the prolonged use of disposable diapers (DDs), the commencement of usage of EC in a child was significantly put off or delayed by parents, and the prevalence of BBD amongst these children increased (P < 0.001). The prevalence of BBD among children who stopped using DDs within the first 12 months and after more than 24 months was 2.79% and 4.38% respectively. Additionally, the prevalence among children who started EC within 12 months after birth and those who never engaged in EC was 1.36% and 15.71% respectively. Early introduction of EC and weaning of DD usage has a positive correlation with lower prevalence of BBD in children in China.
Long noncoding RNA (lncRNA) is a new class of noncoding RNA playing an indispensable role in different diseases by regulating miRNA. Our previous studies have suggested that miR-630 was decreased in patients with cervical cancer. Recently, studies have shown that lncRNA NOC2L-4.1 was abnormally expressed in patients with cervical cancer and can target miR-630. Therefore, we wanted to identify the integrated relationship between lncRNA NOC2L-4.1 and miR-630 in the pathological processes regarding cervical cancer either in vitro or in vivo. Quantitative reverse transcription-polymerase chain reaction detection shows that compared with human normal cervical epithelial cell, the expression of lncRNA NOC2L-4.1 was significantly increased and the expression of miR-630 was decreased in cell lines of cervical cancer. Moreover, luciferase reporter assay showed that miR-630 was a target of lncRNA NOC2L-4.1. The in vitro study found that downregulation of lncRNA NOC2L-4.1 suppressed cervical cancer cell migration (transwell assays) and proliferation (cell counting kit-8 and cloning formation assays). miR-630 specific inhibitor treatment reversed the inhibitory effect of lncRNA NOC2L-4.1 on cell proliferation and migration. Further studies also found that yes-associated protein 1 (YAP1) was the target of miR-630. Overexpression YAP1 suppressed miR-630 overexpression induced cell proliferation and inhibition of migration. Tumors induced by implantation of lncRNA NOC2L-4.1-knockdown Hela cells in nude mice showed that lncRNA NOC2L-4.1 silencing decreased the growth of tumors in both volume and weight by regulation of miR-630/YAP1. Taken together, our study reveals the important role of lncRNA NOC2L-4.1/miR-630/YAP1 regulatory network in cervical cancer, which provides new insights concerning the pathogenesis of cervical cancer.
Background To investigate the prognostic risk factors and postoperative recurrence of bladder cancer in patients with upper urinary tract urothelial carcinomas (UTUCs). Methods Data of 439 UTUC patients were retrospectively analyzed. Follow-up and analysis of smoking effects, consumption of traditional Chinese medicine containing aristolochic acid, history of bladder cancer, age, sex, presence or absence of diabetes mellitus (DM), metformin use, tumor characteristics (number, location, stage, grade), and open or laparoscopic surgery on the prognosis of UTUCs were performed. Cox proportional hazard regression analysis was performed to analyze the relationship between various factors and the postoperative survival rate. The survival rate was analyzed using the Kaplan-Meier method. Moreover, logistic regression analysis was performed to analyze the relationship between the above mentioned factors and postoperative recurrence of bladder cancer. Results Overall, 439 patients met, including 236 males (53.7%) and 203 females (46.3%), the criteria for the final statistical analysis, and the average age was 66.7 years. The 1-, 3-, and 5-year overall survival rates of 439 UTUC patients were 90.0, 76.4, and 67.7%, respectively. The 5-year survival rates of T1, T2, T3, and T4 patients were 90.2%, 78%, 43.8%, and 18.5%, respectively. Factors influencing the long-term survival rate of UTUC patients were smoking, taking traditional Chinese medicine containing aristolochic acid, history of bladder cancer, age, tumor size, tumor stage, tumor grade, and lymph node metastasis. The risk factors related to postoperative bladder cancer recurrence were advanced tumor stage, high grade tumor, preoperative ureteroscopy, ureteral urothelial carcinoma, no postoperative bladder perfusion chemotherapy and DM without metformin use. Conclusions Advanced tumor stage and presence of a high-grade tumor were risk factors for not only poor UTUC prognosis but also BC recurrence. In addition, preoperative ureteroscopy, ureteral urothelial carcinoma and DM without metformin use were high risk factors for BC recurrence, whereas regular postoperative bladder perfusion chemotherapy was a protective factor.
Transmembrane protease serine 4 (TMPRSS4), a type-II transmembrane serine protease, is involved in the development and progression of wide range of tumors. However, the biological role of TMPRSS4 in prostate cancer remains obscure. Here, we investigated the effect of TMPRSS4 on proliferation and migration in prostate cancer and potential mechanisms. Our findings demonstrated over-expression of TMPRSS4 promoted the PC3 prostate cancer cells migration, which could be reversed by TMPRSS4 silencing. TMPRSS4 induced TWIST1 expression and followed progression of EMT along with upregulation of N-cadherin and downregulation of E-cadherin via STAT3 phosphorylation. Silencing TWIST1 significantly attenuated TMPRSS4-induced PC3 migration. Moreover, knockdown of STAT3 effectively attenuated TMPRSS4-induced TWIST1 expression and TWIST1 promoter activity. Taken together, we demonstrated a mechanistic cascade of TMPRSS4 up-regulating STAT3 activation and subsequent TWIST1 expression, leading to prostate cancer migration.
The objective of this study is to investigate the efficacy of silodosin in medical expulsive therapy (MET) for ureteral stones. We conducted a systematic review and meta-analysis to determine the efficacy and safety of silodosin in MET for ureteral calculi. We searched PubMed, Embase, Medline, Central (the Cochrane Library, Issue 1,2013), Google Scholar from the inception to March 2015 for randomized controlled trials (RCTs), comparing silodosin with tamsulosin or control on ureteral stone passage. Eight RCTs with a total of 1145 ureteral stone patients (300 patients in the control group, 287 patients in the tamsulosin group, 558 patients in the silodosin group) were included in this meta-analysis. When compared with control, silodosin significantly improved expulsion rate of distal ureteral stones (RR: 1.42; 95% CI, 1.21–1.67; P < 0.0001), while there was no significant difference between silodosin and the control in expulsion rate of proximal (RR: 0.99; 95% CI, 0.69–1.43; P < 0.97) or mid (RR: 1.13; 95% CI, 0.60–2.16; P < 0.0001) ureteral stones. There was no significant difference between silodosin and tamsulosin in terms of expulsion time (WMD: −2.47; 95% CI, −5.32 to 0.39; P = 0.09), analgesic use (WMD: −0.39; 95% CI, −0.91 to 0.13; P = 0.14) and retrograde ejaculation rate (RR: 1.85; 95% CI, 0.95–3.59; P = 0.07) in MET for distal ureteral stones. However, silodosin provided a significantly higher expulsion rate (RR: 1.25; 95% CI, 1.13–1.37; P < 0.0001) than tamsulosin for distal ureteral stones. Silodosin significantly improved expulsion rate of distal ureteral stones and was clinically superior to tamsulosin. Silodosin was ineffective in MET for proximal and mid ureteral stones. More RCT studies are needed to compare the efficacy of silodosin versus tamsulosin in MET for distal ureteral stones.
OBJECTIVE:The purpose of this study was to investigate the mechanism of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in prostate cancer (PCa) via regulating the miR-218-5p/high mobility group box 1 (HMGB1) axis.METHODS:The Cancer Genome Atlas database was used to divide differentially expressed lncRNAs, microRNAs, and messenger RNA (mRNAs). The mRNA expressions of lncRNA PCA3, miR-218-5p, and HMGB1 were determined by reverse transcription polymerase chain reaction. Cell propagation was evaluated using the Cell Counting Kit-8 assay and the apoptotic rate was examined by flow cytometry. Cell migration and invasion were observed through the wound healing assay and transwell assay. Target relationships among PCA3, miR-218-5p, and HMGB1 were validated via dual-luciferase reporter gene assay. A nude mouse model in vivo was designed to evaluate the effect of PCA3 on prostate tumor growth.RESULTS:PCA3 and HMGB1 were high-expressed in PCa, whereas miR-218-5p was low-expressed. PCA3 knockdown or miR-218-5p overexpression suppressed PCa cell proliferation, migration, and invasion, but promoted apoptosis. Besides, targeted relationships and interactions on the expression between miR-218-5p and PCA3 or HMGB1 were elucidated. PCA3 weakened cell viability and mobility whereas induced apoptosis through binding with miR-218-5p. Meanwhile, miR-218-5p also inhibited PCa tumorigenesis via downregulation of HMGB1. Knockdown of PCA3 impeded tumor growth by downregulating its downstream gene HMGB1.CONCLUSIONS:lncRNA PCA3 facilitated PCa progression through sponging miR-218-5p and regulating HMGB1.
OBJECTIVE:To assess the efficacy of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agent (AA) therapy in the management of paediatric monosymptomatic nocturnal enuresis (MNE) using a network meta-analysis. MATERIALS AND METHODS:We searched the electronic databases PubMed, Cochrane Library, EMBASE and Web of Science from inception to 1 March 2018. Randomized controlled trials (RCTs) that compared desmopressin, alarm, desmopressin plus alarm, and desmopressin plus AAs were identified. The network meta-analysis was conducted with software R 3.3.2 and STATA 14.0. RESULTS:Eighteen RCTs with a total of 1 649 participants were included. The meta-analysis results showed that complete response (CR) and success rates with desmopressin plus AAs were higher than with desmopressin or alarm monotherapy. Success rates for desmopressin plus alarm therapy were higher than for alarm monotherapy. No obvious difference was observed between desmopressin plus AAs and desmopressin plus alarm therapy with regard to CR rate and success rate. The relapse rate with alarm monotherapy was much lower than with desmopressin monotherapy. Adverse events seemed to be infrequently and tolerable for all treatments. The ranking probability results were as follows: desmopressin plus AA ranked first for the outcomes of CR and success, desmopressin plus alarm therapy ranked first for mean number of wet nights per week, and alarm therapy had the lowest relapse rate. CONCLUSIONS:The network meta-analysis showed that desmopressin had similar efficacy to alarm therapy but a higher relapse rate. Desmopressin plus AA therapy was associated with better efficacy than and a similar relapse rate to desmopressin monotherapy. Desmopressin plus alarm therapy was similar to both desmopressin and alarm monotherapy in efficacy. All treatments, including desmopressin plus AAwere associated with tolerable adverse events; however, additional high-quality studies are needed for further evaluation of these treatments.
The influence of hydrogen plasma by ammonia ionization preprocessing of MC-Si solar cells before deposition of SiNx thin films was described. The effect of preprocessing time, RF power, temperature and the pressure were investigated. The short circuit current is 4% higher than before. Then the silicon nitride (SiNx) was deposited for crystalline silicon solar cell by means of plasma enhanced chemical vapor deposition (PECVD), and the results indicated that the hydrogen plasma could walk through the silicon nitride and the carrier lifetime increased about 5��s. The low temperature pretreatment could make the short current increased and the best range is 430-440��C.