Lower urinary tract symptoms (LUTS),consisting storage,voiding and postmicturition symptoms,is a comprehensive definition involving multiple organs.There has been an increasing emphasis on the integrated management of non-neurogenic male lower urinary tract symptoms.Instead of focusing on the enlarged prostate,the current treatment has paid more attention on the entire urinary tract as well as multiple organ factors.Therefore,we provided a literature review and summarized the key points during the management of male LUTS as 3B,namely beyond prostate,beyond surgery and beyond urology.

Objective:To analyze the early changes of gene expression levels and signaling pathways in 661W cell line under hypoxic conditions and to find potential functional target genes.Methods:The cultured mouse 661W cells were divided into hypoxia treatment group and normoxia control group. Cells in the hypoxia treatment group were cultured in a three-gas incubator with volume fraction of 1% and 5% CO 2 at 37 ℃. Cells in the normoxia control group were cultured in an incubator at 37 ℃ with volume fraction of 5% CO 2. High-throughput sequencing technology was used to sequence the transcriptome of 661W cell treated with hypoxia and normoxia for 4 hours to screen for differentially expressed genes (DEG). Clustering heat map analysis, gene ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction network (PPI) analysis were performed. The reverse transcription-polymerase chain reaction (RT-PCR) was used to verify the accuracy of the sequencing results. Results:A total of 506 differentially expressed genes were screened, including 459 up-regulated genes and 47 down-regulated genes. GO functional enrichment analysis showed that the main biological processes of DEG were the cell's response to hypoxia, glycolysis, negative regulation of cell proliferation and apoptosis. hypoxia inducible factor (HIF)-1α pathway, glycolysis, Forkhead box O (FoxO) pathway, Insulin signaling pathway and Adenosine 5′-monophosphate-activated protein kinase (AMPK) pathway were involved in the above process. PPI analysis results showed that hub genes related to hypoxia were Aldoa, Aldoc, Gpi1, Hk2, Hk1, Pfkl, Pfkp, Vhl, Fbxo10 and Fbxo27. The RT-PCR results showed that the relative expression levels of 15 DEG mRNA in the hypoxic treatment group were higher than that of the normoxic control group, and the difference was statistically significant ( P<0.05). The mRNA expression levels of N-myc downstream-regulated gene-1 ( Ndrg1 ), Mt1, and vascular endothelial growth factor A ( VEGFA) were time-dependent on hypoxia. Conclusions:Under hypoxia, DEG is mainly related to glucose metabolism, cell response to hypoxia, regulation of proliferation and apoptosis. HIF-1α pathway, glycolysis, FoxO pathway and AMPK pathway are involved in the early changes of 661W cells under hypoxia. Aldoa, Aldoc, Gpi1, Hk2, Hk1, Pfkl, Pfkp, Vhl, Fbxo10, Fbxo27 may play key roles in the response of 661W cells to hypoxia. Ndrg1, Mt1 and VEGFA could be potential functional target genes for the study of ischemia and hypoxia-related fundus diseases.

Trauma,iatrogenic injury,and neurological disorders can lead to neurogenic lower urinary tract dysfunction (NLUTD).However,there are some special causes in women,including radical hysterectomy,mid-urethral suspension,pelvic organ prolapse repair,Fowler syndrome,interstitial cystitis etc.Traditional behavioral therapy,drug treatment and surgeries may work less well in patients with NLUTD and may even lead to progression and deterioration of the diseases.A review of current literatures revealed that there is an increasing evidence on the application of sacral neuromodulation (SNM) in the treatment of NLUTD in female.This review will provide a summary of the known mechanisms of female NLUTD and the effectiveness of SNM.

Objective To translate the International Consultation on Incontinence Modular Questionnaire for Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) and ICIQ-MLUTS long form (ICIQ-MLUTS LF) into Chinese and assess their metric properties and applicability.Methods After obtaining permission from the International Consultation on Incontinence Questionnaire (ICIQ),original ICIQ-MLUTS and ICIQ-MLUTS LF were translated into Chinese according to ICIQ validation protocol and cultural adaptation guideline.During November 2017 to August 2018,Chinese version of ICIQ-MLUTS and ICIQ-MLUTS LF were tested by administering them in 6 and 12 hospitals in China respectively.To validate the translated questionnaires,the following tests were undertaken.The content validity was determined by indepth interviews with participants and experts.The correlation coefficients of ICIQ-MLUTS and ICIQ-MLUTS LF with International Prostate Symptom Score (IPSS) were assessed to validate criterion validity.Cronbach's alpha test was used to explore internal consistency.And the test-retest reliability was evaluated by calculation of intraclass correlation coefficient.Results In total,Chinese ICIQ-MLUTS and ICIQ-MLUTS LF were administrated to 135 and 230 male patients with lower urinary tract symptoms respectively.Both questionnaires had good content validity and good criterion validity with IPSS (Pearson correlation 0.846 and 0.833 for ICIQ-MLUTS and ICIQ-MLUTS LF respectively,both P ＜ 0.001).The Cronbach's alpha coefficient was 0.797 for ICIQ-MLUTS,and 0.853 for ICIQ-MLUTS LF.Intraclass correlation coefficient was 0.986 and 0.985 respectively (both P ＜ 0.001),showing good test-retest reliability.Conclusions The Chinese version of ICIQ-MLUTS and ICIQ-MLUTS LF had good validity and reliability,which can be used to assess Chinese male patients with lower urinary tract symptoms.

Objective To evaluate the effects of sacral neuromodulation (SNM) on female overactive bladder (OAB) and interstitial cystitis/ painful bladder syndrome (IC/PBS).Methods From May 2016 to April 2017,13 patients with OAB or IC/PBS who had been treated with SNM were assessed retrospectively.Among them,6 cases were OAB patients,and 7 cases were IC/PBS patients.The average age was 52.3 (42-67)years old,and the preoperative and postoperative 24 h urine frequency,night urination frequency and average voided volume were compared.Results Totally 13 patients underwent stage Ⅰprocedure.The operation time for stage Ⅰ was 52-125min(average 92 min).After an average follow-up of 3.6 weeks,stage 11 procedures were performed on responders.Four OAB patients accepted stage Ⅱ1 surgery (conversion rate:66.7％),and the 24h frequency and night urination frequency reduced from preoperative 22.5 and 5.2 times to postoperative 14.3 and 2.3 times (P ＜ 0.05) respectively,and average voided volume increased from 120.3ml to 166.4ml (P ＜ 0.05).Among 4 patients presenting IC/PBS who had underwent stage Ⅱ surgery (conversion rate:57.1％),VAS score and 24 h voiding frequency reduced from 7.3 and 21.6 to 3.8 and 16.8 (P ＜ 0.05),respectively.No adverse event,such as wound infection or electrode translocation was detected during an average follow-up of 8.3 months.Conclusions Stage Ⅰ procedure is crucial for the long term efficacy of SNM.Postsurgical wound management and parameter adjustment are equal essential in order to achieve a maximum benefits.SNM has advantages in minimal invasiveness and less bleeding,which provides a minimal invasive approach for the managemem of OAB and IC/PBS.

Objective To evaluate the clinical efficacy and complications of lattice carbon dioxide laser in the treatment of female mild to moderate stress incontinence.Methods 30 cases of mild to moderate stress urinary incontinence in our hospital from August to October 2017 were reviewed.The average age was (46.5 ±3.5) years old,all married and has been bred,12 patients with mild stress incontinence and 18 patients with moderate stress urinary incontinence.Preoperative preparation including:1h urine cushion test measured leakage of urine,urine flow rate,residual urine,the international consultation on incontinence questionnaire (ICI-Q-SF) score,urine routine examination.Preoperative urine flow rate (31.87 ± 2.42) ml/s,preoperative (1 h) pad test (8.19 ± 2.42) ml,preoperative ICI-Q-SF score (4-8).The power was 12.5 mJ,the efficacy was 25％,and the single treatment was chosen.Urine flow rate,1 h urine pad test,residual urine test,ICI-Q-SF score,and subjective satisfaction were recorded at 1,3,6 months after operation.Results All 30 patients in this group were followed up for more than 6 months.The pad test was (2.14 ± 0.36) ml,(1.02 ± 0.54) ml,(0.80 ± 0.41) ml at 1,3 and 6 months postoperatively,which were significantly different from preoperative pad test (P ＜ 0.01,).The urine flow rate at 1,3,6 months after operation was (30.53 ± 3.15) ml/s,(32.19 ± 2.72) ml/s,(31.23 ± 5.76) ml/s,respectively,and there was no significant difference between the 3 groups (P ＞ 0.05).There was no significant difference between preoperative and postoperative urine flow rate (P ＞ 0.05).The ICI-Q-SF at 1,3,6 months after operation were 3 (1-4),3 (0-4),3 (0-4),which were significantly different from preoperative ICI-Q-SF.Among the 30 patients,3 cases had frequent urination after operation,1 case had frequent urination before operation,and became more severe after operation.The residual urine of 30 patients was negative after operation.All patients had no dysuria and no vaginal bleeding.No signs of urinary incontinence were observed after 6 months follow-up.Conclusions For patients with mild stress urinary incontinence,there is no obvious serious complication in the short term after the laser treatment of dot matrix carbon dioxide laser.The clinical treatment is safe and the leakage of urine can be improved.

Objective:To discover the clinical features of nocturnal enuresis (NE) in adults and to detect factors that correlated with the symptom severity.Methods:This cross-sectional study recruited NE subjects from September 2017 through December 2020. All patients had experienced enuresis at least once per week and with a symptom duration of 3 months or longer. Followed by documentation of history and medical records, three-day bladder diary was adopted to assess their voiding pattern, and urodynamic parameters were obtained to evaluate lower urinary tract function.Results:A total of 106 NE patients (43 male and 63 female) were identified. There is no statistical difference regarding the average age (men: 57.8±15.6 vs. women: 56.1±14.0, P>0.05) and BMI (men: 23.9±3.4 vs. women: 23.3±4.3, P>0.05) between men and women. Comorbidities are extremely common in NE patients (n=85, 80.2%), with the incidence rate higher in men compared to women [88.4% (38/43)vs. 74.6% (47/63), P<0.05]. Hypertension (n=58, 54.7%), hyperlipemia (n=41, 38.7%), diabetes mellitus (n=38, 35.8%), coronary heart disease (n=22, 20.8%) were the most frequently reported conditions. On bladder diaries, subjects were frequently manifested nocturnal polyuria (NP, 47/106, 44.3%), reduced nocturnal bladder capacity (NBC, 74/106, 69.8%), or combination of both(33/106, 31.3%). Urodynamic studies suggested that the incidence of reduce bladder compliance, detrusor overactivity (DO), stress incontinence, bladder outlet obstruction(BOO), detrusor underactivity(DU)and detrusor hyperreflexia with impaired contractility(DHIC)was 27.4%(29/106), 39.6%(42/106), 17.9%(19/106), 9.4%(10/106), 25.5%(27/106)and 15.1%(16/106), respectively. Women were more likely to suffer from stress urinary incontinence [2.3%(1/43) men vs. 28.6% (18/63) women, P<0.01], while men were prone to have bladder outlet obstruction [ 23.3%(10/43) men vs. 0 women, P<0.01]. Correlation analysis demonstrated that obesity( r=0.63, P<0.01), systemic comorbidities( r=0.40, P<0.01), presence of NP( r=0.50, P<0.01) and NP+ NBC( r=0.47, P<0.01), post-void residual( r=0.53, P<0.01), reduced compliance( r=0.21, P=0.04), DU( r=0.28, P<0.01), stress incontinence( r=0.42, P<0.01)and DHIC ( r=0.35, P<0.01)are positively correlated with NE severity. Whereas, reduced Q max( r=-0.35, P<0.01), low capacity( r=0.21, P=0.03), and reduced bladder sensation( r=-0.21, P=0.03) correlate negatively with NE severity. Conclusions:The presence of NE is not only a sign of bladder dysfunction, but also an implication of obesity, systematic chronic diseases, urine production malfunctioning. Therefore, a thorough history regarding the lower urinary tract function and systemic comorbidities should be taken carefully, so that, an integrated and personalized treatment can be carried out.

Objective:To investigate the safety and effectiveness of tension adjustment technique using anatomical landmarks during retropubic midurethral synthetic sling.Methods:The data of 36 consecutive female patients with urinary incontinence, who had underwent retropubic midurethral synthetic sling procedure from January to August 2019 were analyzed retrospectively. The mean age was (60.83±7.93) years old and the body mass index was (24.43±2.44) kg/m 2. Among the recruited subjects, 36 had positive stress test and Marshall-Marchetti test. 20 (55.6%) were pure stress urinary incontinence, and 16 (44.4%) were mixed urinary incontinence. The severity of incontinence was classified into mild (5 cases, 13.9%), moderate (14 cases, 38.9%), severe (13 cases, 36.1%) and very severe (4 cases, 11.1%) using one-hour pad tests. Urodynamics were performed in 17 cases, with 5 (29.4%) presented detrusor overactivity, 3 (17.7%) possessed intrinsic sphincter deficiency. For each case, the tension of the sling was adjusted based on the anatomical landmarks, i. e. using an angled clamp attached closely to the pubic symphysis ventrally and the tip parallel to the edge of hymen dorsally. All patients were catheter-free right after the procedure. The subjective and objective effectiveness, and safety (the rate of urinary retension after surgery and postvoid residual volume 3 months later) were evaluated.The subjective cure rate was was defined as complete leakage free or very mild leakage during excessive bladder filling and fierce cough. The subjective effectiveness was defined as over 50% improvement of the leakage symptom. The objective cure rate was defined as a negative stress test. Results:For all 36 patients, the median hospital stays was 8 (5-95)h. No bladder perforation or transfusion cases. All patients were catheter-free right after the procedure, with no incidence of urinary retention. 27 patients completed a 3-month follow-up, with 22 had post-void residual data, 23 had subjective effectiveness data and 23 had objective effectiveness data. The median post-void residual was 7.5 (5-64) ml, subjective cure rate was 91.3% (21/23), and objective cure rate was 95.7% (22/23). 8.7% (2/23) reported difficult urination alleviated without the necessity of clinical interference. No urethra erosion or vagina extrusion was found. At 2-year follow-up, 34 patients completed assessment by phone. The subjective cure rate was 91.2% (31/34), with only 2.9% (1/34) reported difficult urination. Besides, at 3-month follow-up, there was no difference regarding the subjective cure rate [100.0%(12/12) vs. 81.8%(9/11)]or objective cure rate [91.7%(11/12) vs. 100.0%(11/11)] between patients with stress and mixed incontinence. No difference was noted among patients with mild, moderate, severe and very severe leakage[75.0% (3/4) vs. 100.0%(6/6) vs. 90.0%(9/10) vs. 100.0%(3/3)]. Of the 12 cases with urodynamic records, the presence of detrusor overactivity [66.7%(2/3) vs. 88.9%(8/9)] or intrinsic sphincter deficiency [0(0/1) vs. 90.9%(10/11)] did not significantly affected the cure rate of the procedure. At 2-year follow-up, there was no difference regarding the subjective cure rate between patients with stress and mixed incontinence [94.7%(18/19) vs. 86.7%(13/15)]. No difference was also noted among patients with mild, moderate, severe and very severe leakage[80.0%(4/5) vs. 100.0%(13/13) vs. 83.3%(10/12) vs. 100.0%(4/4)]. Of the 16 cases with urodynamic records, the presence of detrusor overactivity [60.0%(3/5) vs. 90.9%(10/11)]or intrinsic sphincter deficiency [66.7%(2/3) vs. 84.6%(11/13)]did not significantly affected the cure rate of the procedure.Conclusions:Tension adjustment using anatomic landmarks during sling procedure is safe and feasible for urinary incontinence, with minimum complications and residual volume, and high subjective/objective cure rate.

Objective:To analyze differentially expressed genes (DEGs) and the changes of signal pathways in human retinal pigment epithelium cells (ARPE-19) under hypoxic and normoxic conditions and to explore the biological mechanism of hypoxia-induced ARPE-19 cell damage via transcriptome sequencing (RNA-seq) and bioinformatics technology.Methods:The ARPE-19 cells were divided into the hypoxia treatment group and the normoxia control group treated with 1% and 21% O 2 by volume for 8, 24, 48, 72 hours, respectively.The relative expression levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) mRNA were detected with real-time fluorescent quantitative PCR at different time points.RNA-seq and bioinformatics analysis were performed at 8 hours and 24 hours after hypoxia and normoxia treatment.DEGs were screened out under the conditions of |log 2FC|≥1 and P≤0.05.Then the cluster heat map analysis, Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction network analysis were also carried out.Real-time fluorescent quantitative PCR was employed at 24 hours after hypoxia to detect the relative mRNA expression of genes that might be related to hypoxia in DEGs.Cell viability kit was used to verify and compare the damage effect of hypoxia on ARPE-19 cells at different time points between the two groups. Results:The relative mRNA expression levels of VEGF at 8, 24, 48 and 72 hours after hypoxia treatment and the relative HIF-1α mRNA expression levels at 8, 24 and 48 hours after hypoxia treatment were significantly higher than those of the normoxia control group (all at P<0.05). There were large differences in the mRNA expression levels at 8-hour and 24-hour treatment between the two groups.A total of 62 significant DEGs were screened between the hypoxia treatment group and the normoxia control group after 8-hour hypoxia treatment, among which 45 genes were significantly up-regulated and 17 genes were significantly down-regulated.A total of 255 significant DEGs were screened out between the hypoxia treatment group and the normoxia control group after 24-hour hypoxia treatment, among which 228 genes were significantly up-regulated and 27 genes were significantly down-regulated.The GO functional analysis of DEGs was mainly enriched in processes such as protein degradation, nucleotide biosynthesis, and material transport.KEGG pathway analysis was mainly enriched in PI3K-Akt, cGMP-PKG, and other signaling pathways closely related to metabolism, cell cycle, cell growth, and apoptosis.The core genes HPCA, MT3 and NOS3 were found by protein-protein interaction network analysis.Real-time fluorescent quantitative PCR test results showed that after 24-hour hypoxia treatment, the mRNA expression levels of hypoxia related genes DEPP1, NPPB, PDZK1, HILPDA, TCEA3, NDRG1 and RORC in ARPE-19 cells were significantly increased and the mRNA expression levels of TFRC and NQO1 were significantly decreased (all at P<0.05). The cell morphology was normal and the growth state was good without dead cells after 8-hour and 24-hour hypoxia treatment in ARPE-19 cells.There were dead cells after 48-hour hypoxia treatment, and the number of dead cells was increased at 72 hours after hypoxia treatment. Conclusions:The PI3K-Akt and cGMP-PKG signaling pathways related to metabolism may be involved in hypoxia-induced injury of ARPE-19 cells.Core genes of HPCA, MT3 and NOS3 can be used as functional target genes and play key roles in hypoxia response of cells.

Objective:To analyze the change of differential genes and signaling pathways in high glucose induced BV2 cells, and to explore the mechanism of transgelin-2 (TAGLN2) regulating cellular inflammatory response and metabolic process.Methods:An experimental study. The cultured BV2 cells were divided into mannitol treatment (Man) group, glucose treatment (Glu) group, overexpression control Glu treatment (Con) group, overexpression TAGLN2 Glu treatment group, silence control Glu treatment (shCon Glu) group, and silence TAGLN2 Glu treatment (shTAGLN2 Glu) group. Cells in the Man group were cultured in modified Eagle high glucose medium (DMEM) containing 25 mmol/L mannitol and 25 mmol/L glucose, cells in other groups (Glu group, Con Glu group, TAGLN2 Glu group, shCon Glu group and shTAGLN2 Glu group) were cultured in DMEM medium containing 50 mmol/L glucose. After 24 hours of cells culture, transcriptome sequencing of cells in each group were performed using high-throughput sequencing technology, and significantly differentially expressed genes (DEG) were screened. |log 2 (fold change)|≥1 and P≤0.05 were adopted as criteria to screen for DEG. Gene Ontology (GO) function enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction network analysis were performed. Real-time polymerase chain reaction (RT-PCR) was used to detect the relative expression level of DEG mRNA. The data between groups were compared by independent sample t-test. Results:When compared with Man group, a total of 517 differentially expressed genes were screened in Glu group, which including 277 up-regulated genes and 240 down-regulated genes. KEGG pathway enrichment analysis showed that the up-regulated genes were significantly enriched in immune system processes such as nuclear factor (NF)-κB signal pathway, Jak-signal transducers and activators of transcription (STAT) signal pathway, while down-regulated genes were significantly enriched in glycosaminoglycan degradation and glyceride metabolic pathway. Compared with Con Glu group, a total of 480 DEG were screened in TAGLN2 Glu group, among which 147 up-regulated and 333 down-regulated genes were detected. Up-regulated genes were significantly enriched in the metabolic processes of fatty acid, glyceride and pyruvate, while down-regulated genes were significantly enriched in immune system processes such as NF-κB signal pathway, Jak-STAT signal pathway and tumor necrosis factor (TNF) signal pathway. Compared with shCon Glu group, a total of 582 DEG were screened in shTAGLN2 Glu group, among which 423 up-regulated and 159 down-regulated genes were detected. Up-regulated DEG were significantly enriched in immune system processes such as TNF signal pathway and chemokine signal pathway, while down-regulated DEG were significantly enriched in pattern recognition receptor signal pathway. RT-PCR results showed that the relative expression levels of DEG mRNA Card11 ( t=13.530), Icos ( t=3.482), Chst3 ( t=6.949), Kynu ( t=5.399), interleukin (IL)-1β ( t=2.960), TNF-α ( t=5.800), IL-6 ( t=3.130), interferon-γ ( t=7.690) and IL-17 ( t=6.530) in the TAGLN2 Glu treatment group were decreased significantly compared with Con Glu group, and the difference was statistically significant. Conclusion:TAGLN2 can inhibit glucose induced microglia inflammation by NF-κB and Jak-STAT signaling pathways, Card11, Icos, Chst3 and Kynu play an important role in the anti-inflammatory process of TAGLN2.