ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis.

This study investigated the mechanism of action of ABT-263 in the treatment of neurogenic bladder fibrosis (NBF)and its protective effects against upper urinary tract damage (UUTD). Sixty 12-week-old Sprague-Dawley (SD) rats were randomly divided into sham, sham + ABT-263 (50 mg/kg), NBF, NBF + ABT-263 (25 mg/kg, oral gavage), and NBF + ABT-263 (50 mg/kg, oral gavage) groups. After cystometry, bladder and kidney tissue samples were collected for hematoxylin and eosin (HE), Masson, and Sirius red staining, and Western Blotting (WB) and qPCR detection. Primary rat bladder fibroblasts were isolated, extracted, and cultured. After co-stimulation with TGF-ß1 (10 ng/mL) and ABT-263 (concentrations of 0, 0.1, 1, 10, and 100 µmol/L) for 24 h, cells were collected. Cell apoptosis was detected using CCK8, WB, immunofluorescence, and annexin/PI assays. Compared with the sham group, there was no significant difference in any physical parameters in the sham + ABT-263 (50 mg/kg) group. Compared with the NBF group, most of the markers involved in fibrosis were improved in the NBF + ABT-263 (25 mg/kg) and NBF + ABT-263 (50 mg/kg) groups, while the NBF + ABT-263 (50 mg/kg) group showed a significant improvement. When the concentration of ABT-263 was increased to 10 µmol/L, the apoptosis rate of primary bladder fibroblasts increased, and the expression of the anti-apoptotic protein BCL-xL began to decrease.ABT-263 plays an important role in relieving NBF and protecting against UUTD, which may be due to the promotion of myofibroblast apoptosis through the mitochondrial apoptosis pathway.

Activation of the TGF-ß1/Smads/α-SMA pathway is related to histological and functional changes in children with neurogenic bladder.

This research is to investigate the expression of the TGF-ß1/Smads/α-SMA pathway and its effect on bladder histology and function in children with neurogenic bladder (NB). The bladder specimens from 10 children with NB and 8 children with vesicoureteral junction obstruction were collected into the NB and control groups. The expression of TGF-ß1, Smad2, Smad3, Smad4, Smad6, α-SMA, fibronectin, collagen I and collagen III in bladder tissues was detected. In addition, the histological characteristics of the bladder were evaluated. A preoperative urodynamic study was performed on all children with NB. We analysed the correlations among the expression of the marker protein a-SMA in myofibroblasts, effector cells of the pathway, and bladder function parameters. Compared with those in the control group, the expression of TGF-ß1, Smad2, Smad3, Smad4, α-SMA, fibronectin, collagen I and collagen III was significantly increased in the NB group, while the expression of Smad6 was decreased (p < 0.01). HE and Masson staining in the NB group showed increased collagen levels and hypertrophy of smooth muscle cells. Children with NB had a low bladder volume ratio (BVR), low compliance (△C) and high maximum bladder pressure, low maximum flow rate, large postvoid residual volume, low bladder contraction index and low bladder voiding efficiency. The expression of α-SMA was negatively correlated with the BVR (r = - 0.7066, P = 0.0223) and △C (r = - 0.6516, P = 0.0412). We conclude that the TGF-ß1/Smads/α-SMA pathway is activated in the bladder tissue of children with NB and may be involved in the processes causing histological and functional changes.

A Study of Urodynamic Parameters at Different Bladder Filling Stages for Predicting Upper Urinary Tract Dilatation.

PURPOSE: To identify more accurate predictors of upper urinary tract dilatation (UUTD) in neurogenic bladder (NB) children, we studied the relationship among urodynamic parameters at different bladder filling stages, detrusor leak point pressure (DLPP) and UUTD. METHODS: A total of 158 children (3-16 years) with NB were included and then divided into 2 groups according to whether their NB diagnosis was complicated with UUTD: the UUTD group (39 patients) and those without UUTD group (control group, 119 patients). The bladder filling phase was divided into 3 equal parts: the early, middle, and end filling stages. The bladder compliance (BC) and detrusor pressure (△Pdet) at each phase and DLPP at the end filling stage were recorded. RESULTS: A BC<8 mL/cm H2O both in the middle and end stages is more specific than a BC<9 mL/cm H2O in the end stage (72%, 73%, vs. 66%), and △Pdet >8 cm H2O in the early stage, 20 cm H2O in the middle stage and 25 cm H2O in the end stage are more sensitive than △Pdet >40 cm H2O in the end stage (82%, 85%, 85%, vs. 49%). A DLPP cutoff value of 20 cm H2O showed higher sensitivity for predicting UUTD than 40 cm H2O. CONCLUSION: Low BC and a high △Pdet in the middle and end filling stages are more accurate factors than classic indicators for predicting UUTD. In addition, a DLPP value of >20 cm H2O in the end bladder filling stage shows high sensitivity.

Prevalence, Risk Factors, and Psychological Effects of Overactive Bladder in Chinese University Students.

PURPOSE: The purpose of this study was to investigate the prevalence and risk factors of overactive bladder (OAB) in young adults and to explore the influence of OAB on mental health. METHODS: Between October 2019 and January 2020, 14,010 anonymous questionnaires were distributed to freshmen at 2 universities in Henan, China. The students came from all over the country. The questionnaire included general items and information necessary to calculate the overactive bladder symptom score, the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) score, Self-Esteem Scale (SES) score, and Self-Rating Depression Scale (SDS) score. The relationships between the prevalence of OAB and its risk factors were evaluated. RESULTS: The overall prevalence of OAB was 6.0%, with 4.3% of participants characterized as having dry OAB and 1.7% as having wet OAB. The prevalence of mild OAB was 5.5%, and that of moderate OAB was 0.5%; no severe OAB was observed. Higher prevalence rates of OAB were found among women, respondents with constipation, and respondents with primary nocturnal enuresis (PNE) (P <0.05). Compared to healthy controls, the OAB group exhibited a higher mean SDS score (52.12±8.986 vs. 47.71±9.399, P<0.001) and mean PSQI score (5.28±2.486 vs. 4.27±2.431, P<0.001), but a lower mean SES score (27.78±3.599 vs. 29.57±4.109, P<0.001). CONCLUSION: OAB significantly affects the mental health of young adults. Female sex, constipation, and PNE are risk factors for OAB.

Serum complement factor B is associated with disease activity and progression of idiopathic membranous nephropathy concomitant with IgA nephropathy.

PURPOSE: Few studies have reported the roles of the complement system in concomitant idiopathic membranous nephropathy and IgA nephropathy (IMN-IgAN). Complement factor B (CFB) is a crucial factor that involved in the alternative complement pathway. We aimed to evaluate the association between disease activity (eGFR, anti-PLA2R antibody levels and 24 h urinary protein excretion), progression and serum CFB levels of IMN-IgAN patients. METHODS: In total, 39 IMN-IgAN patients (median follow-up, 46.6 months), 99 IMN patients and 92 IgAN patients participated in this study. The disease progression event was defined as end-stage renal disease (ESRD) or a 30% decline in estimated glomerular filtration rate (eGFR). The serum CFB concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Serum CFB levels were lower in IMN-IgAN patients than in patients with IgAN only (P < .001). Serum CFB levels correlated positively with serum creatinine levels, anti-PLA2R antibody levels and 24 h urinary protein excretion (P < .05). Kaplan-Meier analysis revealed that IMN-IgAN patients with high serum CFB levels had a significantly lower cumulative renal survival rate than patients with low levels (log-rank test, P = .009). Multivariate Cox regression analysis showed that high baseline serum CFB levels were significantly associated with poor renal outcome in patients with IMN-IgAN (HR: 2.727, 95% CI 1.076-6.913, P = .034). CONCLUSION: High serum CFB levels correlated with increased serum creatinine, anti-PLA2R antibody and urinary protein excretion as well as poor renal prognosis in patients with IMN-IgAN, indicating that serum CFB may be a marker of disease activity and progression.

Delayed elimination communication is a crucial factor in disposable diaper dependence in Chinese preschool-aged children.

Purpose: Elimination communication (EC) is considered to be a milestone in a child's development. Nowadays, a trend toward an older age at EC initiation has been observed globally, probably due to the convenience of disposable diaper use in daily life. The study aimed to identify potential risk factors for disposable diaper dependence (DDD) and evaluate whether an early/proper EC can reduce the risk of DDD among children in China. Methods: A cross-sectional study was performed on 13,500 children in mainland China from October 2019 to March 2020. An anonymous questionnaire was used to collect information including the sociodemographic characteristics, details about DDD and EC, and the effect of DDD on the quality of life of children. Data were analyzed by SPSS and R software. Results: The overall prevalence of DDD was 4.17% (4.31% in boys; 4.02% in girls) and decreased with age, from 8.71% at 2 years to 0.73% at 6 years (χ 2 trend = 210.392, P < 0.001). In univariable analysis, age, location or EC were associated with DDD. Four independent factors-age, location (urban), caregivers with high education levels (junior college or above) and delayed EC (after 12 months of age)-were identified to be significantly associated with DDD risk in logistic regression model. Compared with EC onset after 12 months of age, EC onset before 12 months of age was associated with a 79.6% (model 2) reduction in DDD. Four independent factors were selected to establish the nomogram for DDD based on the results of logistic regression analysis. The C-index (0.770) and the AUC (>0.7) indicated satisfactory discriminative ability of the nomogram. The calibration diagrams showed favorable consistency between the prediction of the nomogram and actual observations. Conclusion: Our findings indicate the joint contribution of age, location, caregivers' education level and EC to DDD in Chinese preschool-aged children. Timely cessation of the use of disposable diapers and early/proper EC may help to reduce the risk of DDD in children.

Histamine H3 Receptor Signaling Regulates the NLRP3 Inflammasome Activation in C2C12 Myocyte During Myogenic Differentiation.

NLRP3 inflammasome has been implicated in impaired post-injury muscle healing and in muscle atrophy. Histamine receptors play an important role in inflammation, but the role of histamine H3 receptor (H3R) in myocyte regeneration and in the regulation of NLRP3 inflammasome is not known. We studied the effects of H3R signaling on C2C12 myocyte viability, apoptosis, and tumor necrosis factor alpha (TNFα)-induced NLRP3 inflammasome activation during striated myogenic differentiation at three time points (days 0, 3, and 6). Expression of Nlrp3, interleukin-1ß (IL-1ß), and myogenesis markers were determined. TNFα reduced overall viability of C2C12 cells, and exposure to TNFα induced apoptosis of cells at D6. Activation of H3R had no effect on viability or apoptosis, whereas inhibition of H3R increased TNFα-induced apoptosis. Stimulation of C2C12 cells with TNFα increased Nlrp3 mRNA expression at D3 and D6. Moreover, TNFα reduced the expression of myogenesis markers MyoD1, Myogenin, and Myosin-2 at D3 and D6. H3R attenuated TNFα-induced expression of Nlrp3 and further inhibited the myogenesis marker expression; while H3R -blockage enhanced the proinflammatory effects of TNFα and increased the myogenesis marker expression. TNFα-induced secretion of mature IL-1ß was dependent on the activation of the NLRP3 inflammasome, as shown by the reduced secretion of mature IL-1ß upon treatment of the cells with the small molecule inhibitor of the NLRP3 inflammasome (MCC950). The activation of H3R reduced TNFα-induced IL-1ß secretion, while the H3R blockage had an opposite effect. In conclusion, the modulation of H3R activity regulates the effects of TNFα on C2C12 myocyte differentiation and TNFα-induced activation of NLRP3 inflammasome. Thus, H3R signaling may represent a novel target for limiting postinjury muscle inflammation and muscle atrophy.

METTL3/N6-methyladenosine/ miR-21-5p promotes obstructive renal fibrosis by regulating inflammation through SPRY1/ERK/NF-κB pathway activation.

Renal fibrosis induced by urinary tract obstruction is a common clinical occurrence; however, effective treatment is lacking, and a deeper understanding of the mechanism of renal fibrosis is needed. Previous studies have revealed that miR-21 impacts liver and lung fibrosis progression by activating the SPRY1/ERK/NF-kB signalling pathway. However, whether miR-21 mediates obstructive renal fibrosis through the same signalling pathway has not been determined. Additionally, studies have shown that N6-methyladenosine (m6 A) modification-dependent primary microRNA (pri-microRNA) processing is essential for maturation of microRNAs, but its role in the maturation of miR-21 in obstructive renal fibrosis has not yet been investigated in detail. To address these issues, we employed a mouse model of unilateral ureteral obstruction (UUO) in which the left ureters were ligated for 3, 7 and 14 days to simulate the fibrotic process. In vitro, human renal proximal tubular epithelial (HK-2) cells were transfected with plasmids containing the corresponding sequence of METTL3, miR-21-5p mimic or miR-21-5p inhibitor. We found that the levels of miR-21-5p and m6 A modification in the UUO model groups increased significantly, and as predicted, the SPRY1/ERK/NF-kB pathway was activated by miR-21-5p, confirming that miR-21-5p plays an important role in obstructive renal fibrosis by enhancing inflammation. METTL3 was found to play a major catalytic role in m6 A modification in UUO mice and drove obstructive renal fibrosis development by promoting miR-21-5p maturation. Our research is the first to demonstrate the role of the METTL3-m6 A-miR-21-5p-SPRY1/ERK/NF-kB axis in obstructive renal fibrosis and provides a deeper understanding of renal fibrosis.

Mechanism and Priority of Botulinum Neurotoxin A versus Sacral Neuromodulation for Refractory Overactive Bladder: A Review.

BACKGROUND: The treatment of common overactive bladder (OAB) has reached a consensus, but there is not a clear answer to the treatment of refractory OAB (ROAB). ROAB is defined as nonresponsive to treatment with behavioural and oral therapies. The disease can influence the physical and mental health of patients, cause poor quality of life, and create an urgent socio-economic burden. With the advancement of medical treatment, the treatment of OAB has improved significantly in the last 2 decades, especially ROAB, by the usage of botulinum neurotoxin A (BoNT-A) and sacral neuromodulation (SNM). Many studies have demonstrated their effectiveness and safety. However, which therapy is the optimal method remains unclear for patients with ROAB, and the exact mechanism involved in the procedures is still unknown. SUMMARY: This review is to clarify the mechanisms, advantages, and disadvantages of SNM and BoNT-A in treatment of ROAB, and determine whether there is an order effect of SNM and BoNT-A in managing ROAB. Key Messages: BoNT-A and SNM mainly act on the peripheral nervous system and central nervous system, respectively. But BoNT-A and SNM may partly act on the central and peripheral nervous systems, separately. SNM may be a better choice than BoNT-A in the long time. At the same time, BoNT-A and SNM can treat the ROAB as the first and next steps, and the sequence of both would not affect the effectiveness of each other.

Delayed elimination communication on the prevalence of children's bladder and bowel dysfunction.

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.

Prevalence, Risk Factors, and Psychological Effects of Primary Nocturnal Enuresis in Chinese Young Adults.

PURPOSE: This study aimed to investigate the prevalence, risk factors, and effects of primary nocturnal enuresis (PNE) on physical and mental health in young adults in mainland China. METHODS: An anonymous questionnaire was used to collect information including the sociodemographic characteristics, history of PNE, family history, daytime voiding symptoms, Pittsburgh Sleep Quality Index (PSQI) scores, Self-Esteem Scale (SES), and Self-Rating Depression Scale (SDS). A total of 22,500 university students from 23 provinces and 368 cities in mainland China were included. RESULTS: In total, 21,082 questionnaires were collected, and 20,345 of them qualified for statistical analysis. The PNE prevalence was 1.17%, and the distribution of monosymptomatic nocturnal enuresis (MNE) and nonmonosymptomatic nocturnal enuresis (NMNE) was 66.1% and 33.9%, respectively. In total, 28% of respondents with PNE reported bedwetting daily, 31.6% between 1 and 7 times weekly, and 40.4% between 1 and 4 times monthly; 80% of PNE cases had no history of treatment. The prevalence of PNE in patients with a family history, frequency, urgency, urinary incontinence, and recurrent urinary tract infections was significantly higher than in those without these conditions (P<0.001). PNE was significantly correlated with the PSQI total score (sleep quality) (P=0.011). The SES score was lower and the SDS was higher (P<0.001) in the PNE group than in those without PNE. CONCLUSION: In mainland China, the PNE prevalence among young adults was found to be high, and PNE had significant effects on physical and mental health. Risk factors included a family history, daytime voiding symptoms, and lack of treatment.

The TGF-ß1 pathway is early involved in neurogenic bladder fibrosis of juvenile rats.

BACKGROUND: This study investigated whole neurogenic bladder's progression changes, as well as the expression of TGF-ß1 fibrosis pathway-related proteins in bilateral spinal nerve-amputated juvenile rats. METHODS: Sixty-four 8-week-old rats (32 bilateral L6 + S1 spinal nerve amputated and 32 sham operated) were selected. Cystometry was performed. General assessments, Masson, Sirius red, immunohistochemical staining, and western blotting of fibrosis and TGF-ß1 pathway-related proteins were conducted using bladder tissues. RESULTS: Cystometry results showed that the basal intravesical pressures and bladder capacities in nerve-amputated rats were significantly higher than those in sham-operated ones. Compared to the sham-operated groups, the bladder size and wall thickness in the nerve-amputated groups increased initially but then decreased over time. However, bladder weight continuously increased over time. Disintegration, thickening, and hypertrophy of the bladder wall were found over time in the amputated rats. Moreover, there was a significant increase in collagen III, and the ratio of collagen III/I was higher in amputated rats (P < 0.01). Finally, the expression of TGF-ß1, TGF-ßRI, Smad2, and collagen III and I increased in amputated bladder tissues, while Smad6 decreased over time. CONCLUSIONS: The main clinical features of pediatric neurogenic bladder (PNB) were detrusor paralysis and continuous intravesical pressure. Biological molecular findings are earlier than the pathophysiological findings. Therefore, early preventing bladder fibrosis by targeting TGF-ß1/Smad pathway-related proteins once knowing the PNB diagnosis might be an alternative treatment for PNB. IMPACT: The study found that the main clinical features of PNB were detrusor paralysis, continuous intravesical pressure, and increased TGF-beta/Smad signal proteins over time. The study makes contributions to the literature because it suggests biological molecular findings are earlier than the pathophysiological findings by various staining in PNB. The study investigated whole neurogenic bladder's progression changes, as well as the expression of TGF-ß1 fibrosis pathway-related proteins in the spinal nerve-injured PNB juvenile rat models, which suggests that early prevention of bladder fibrosis by targeting TGF-ß1/Smad pathway-related proteins once knowing the PNB diagnosis might be an alternative treatment for pediatric neurogenic bladder.

Disposable diaper overuse is associated with primary enuresis in children.

This research investigated the association between prolonged disposable diaper (DD) wearing in infancy and primary enuresis (PNE). As a case-control study, we collected data from 376 children with enuresis and 379 healthy children who were sex- and age-matched at three tertiary care institutions in mainland China from August 2017 to July 2018. The results of adjusted logistic regression showed the odds ratios (95% confidence intervals) for PNE across the categories of age of daytime DD use cessation were as follows: ≥ 25 months: 1.00, 18-24 months: 0.25 (0.17-0.37), and ≤ 17 months: 0.11 (0.06-0.20), independent of age, mother education, residence, toilet training approach, breastfeeding duration, UTI, constipation, anaphylactic disease and family history. After a similar multivariable adjustment, increased age of daytime DD use (per-month) had a positive correlation with PNE, OR = 1.17, 95% CI 1.13-1.20 and non-linear relationship was detected, whose point was 21 months (the effect sizes and the 95%CI on the left and right sides of inflection point were 1.04 (0.99-1.10), P = 0.131 and 1.25 (1.18-1.31), P < 0.001). Subgroup analysis found that the effect of duration of disposable diaper exposure for each additional month, those children had accepted assisted infant toilet training/elimination communication (AITT/EC) practice had a lower risk of PNE (OR = 1.08, 95% CI 1.04-1.12), compared with those without AITT/EC practice (OR = 1.20, 95% CI 1.14-1.27), P for interaction < 0.001. In conclusion, the children diagnosed with primary enuresis after age 5 stopped using disposable diapers at daytime later than the control group. Association between duration of DD exposure and the risk of childhood enuresis is modified by AITT/EC practice. Timely cessation use of disposable diaper and practice AITT/EC may shorten the time to nocturnal continence, and the prospective cohort studies are needed to verify the discoveries.

EGFRvIII-specific CAR-T cells produced by piggyBac transposon exhibit efficient growth suppression against hepatocellular carcinoma.

Adoptive cellular immunotherapy employing chimeric antigen receptors-modified T (CAR-T) cells has demonstrated promising antitumor effects in hematologic cancers. However, CAR-T therapy confront many challenges in solid tumors like immunosuppressive microenvironment, molecular heterogeneity, etc. The cancer genome atlas (TCGA) of hepatocellular carcinoma (HCC) revealed many genetic characteristic and molecular tumorigenesis. EGFRvIII is a tumor specific antigen widely expressed in a variety of cancers including HCC and an ideal therapeutic target for cancer therapy. The liver cancer cell line SMMC7721 express high level EGFRvIII and widely applied in HCC investigations. Herein, we developed EGFRvIII CAR-T cells by piggyBac transposon system, and detected its specific killing effect against SMMC7721 cells in vitro and in vivo. Results indicated that transduction efficiency of CAR reached 53.1%. Expression of CAR protein was verified by immunoblotting as a band of approximate 57KD. The killing effect of CAR-T cells against SMMC7721 was positively correlated with E/T ratio (E:T=5:1, 10:1, 20:1, 40:1), and exceeded 50% at 20:1 ratio. Significant increase in IFN-γ and TNF-α secretion were detected in the co-culture supernatant of CAR-T cells and SMMC7721, comparable to the level of exogenous EGFRvIII-expressing U87 cells. The killing activity and cytokine secretion were both dependent on the expression level of EGFRvIII in target cells. In HCC xenograft models, CAR-T cells could effectively suppress the growth of SMMC7721. In conclusion, EGFRvIII CAR-T cells demonstrated specific antitumor effect against SMMC7721 in vitro and in vivo, providing basis for immunotherapy of HCC in future clinical use.

Delayed in toilet training association with pediatric lower urinary tract dysfunction: A systematic review and meta-analysis.

BACKGROUND: Globally, attitudes and practices towards toilet training have changed several decades ago and children are completing toilet training at a later age compared to previous generations. Concurrently, there has been an increase in the incidence of pediatric bladder bowel dysfunction (BBD), including lower urinary tract dysfunction (LUTD). Whether the fact of delayed toilet training may negatively impact the ability of children to obtain bladder and bowel control and cause LUT dysfunction remains controversial. OBJECTIVES: To investigate the association between age at initiation of toilet training or approach to toilet training and the risks of lower urinary tract (LUT) dysfunction. METHODS: A comprehensive search of the CENTRAL, EMBASE and MEDLINE via Ovid SP, and CINAHL via EBSCO databases was conducted to identify RCTs, cohort or case-control studies investigating the association between age at initiation of toilet training, approach used for toilet training, and pediatric LUT dysfunction. RESULTS: A total of 10 studies with 24,121 participants (aged 5-17) were included for pooled analysis. Overall, the odds ratio (OR) with 95% confidence interval (95%CI) of LUT dysfunction in children who initiated toilet training at a younger age when compared to those who initiated toilet training at an older age, was 0.71 (0.63-0.81), P < 0.001), irrespective of the approach used for toilet training (Table). Subgroup analysis for day-time incontinence (persistent daytime wetting) was 0.77 (0.62-0.95), P = 0.014; although the outcomes for enuresis fluctuated, favorable results were still observed in the earlier training group (OR:0.63, 95%CI:0.43-0.94, P = 0.023). Subgroup analysis for age at initiating toilet training vs LUT dysfunction also showed favorable results in children who were trained earlier, i.e., before 24 months (OR:0.77, 95% CI 0.63-0.94, P = 0.009). Sensitivity analysis confirmed that the results were robust. DISCUSSION: Although the definition about the age of initial toilet training varied greatly in studies, findings from the current study suggested that the optimal time for initiating toilet training may be prior to the age of 24 months; if toilet training was initiated after 24 months or later, it may result in increased prevalence of LUT dysfunction. Since no RCTs studies were included in the current meta-analysis, well-designed longitudinal studies with larger sample size and from different cultural background are needed to confirm these results. CONCLUSION: This meta-analysis presents preliminary findings that show the incidence of LUTD may be decreased by initiating toilet training in children at a younger age.

Prevalence and risk factors of overactive bladder in Chinese children: A population-based study.

AIMS: To investigate the prevalence of overactive bladder (OAB) and assess its risk factors in 5- to 14-year-old Chinese children. METHODS: A cross-sectional study of OAB prevalence was performed by distributing 11 800 anonymous self-administered questionnaires to parents in five provinces of mainland China from July to October 2018. The questionnaires included questions on sociodemographics, history of urinary tract infection (UTI), lower urinary tract symptoms (LUTS), family history of LUTS, bowel symptoms, and details about the elimination communication (EC) start time. OAB was defined as urgency and increased the daytime frequency with or without urinary incontinence. RESULTS: A total of 10 133 questionnaires qualified for statistical analysis. The overall prevalence of OAB was 9.01% and decreased with age, from 12.40% at 5 years to 4.55% at 14 years (χ2 trend = 88.899; P < .001). The proportion of dry OAB increased with age, whereas the proportion of wet OAB decreased. A late-onset of EC was associated with a high OAB prevalence (χ2 trend = 39.802; P < .001). Children with obesity, a history of UTI, nocturnal enuresis (NE), a family history of LUTS, constipation, and fecal incontinence had a higher prevalence of OAB than did normal children (P < .05). CONCLUSION: Obesity, a history of UTI, NE, a family history of LUTS, and bowel symptoms are risk factors associated with OAB. Starting EC before 12 months of age might help reduce the prevalence of OAB in children.

Changes in bladder function with time following cystostomy in rats.

AIMS: To investigate bladder function patterns following cystostomy and determine the best time window for cystometric evaluation of bladder function in conscious rats. MATERIALS AND METHODS: Cystostomy was performed in rats of the first seven groups; thereafter, cystometry was performed in the designed time interval. Noncystostomy rats of group 8 voided freely as control. Basal bladder pressure (Pves.basal ), maximum bladder pressure (Pves.max ), bladder threshold pressure (Pves.thre ), voiding interval (VI), bladder contraction duration (CD), bladder compliance (ΔC), voided volume (VV), postvoiding residual urine (PVR), and bladder capacity (BC) were recorded and compared with cystostomy groups, with VV, PVR, BC compared with the control values. Bladders were collected after the urodynamic study for weighing, hematoxylin-eosin, and Masson staining to investigate pathological changes. RESULTS: Pves.basal , Pves.max , and Pves.thre trended downward, while BC, VI, VV, and ΔC trended upward on days 1 to 5 postcystostomy. BC and VV significantly decreased on days 1 to 3 postcystostomy compared with control values; on days 5 to 15 postcystostomy, Pves.basal , Pves.max , Pves.thre , VI, VV, BC, and PVR were stable, and BC, VV, and PVR showed no significant differences from the control values. However, on day 21 postcystostomy, BC increased significantly compared with the controls. Bladder weight increased in the cystostomy groups compared with the controls. Pathological analysis showed severe acute bladder inflammation on days 1 to 3, mild inflammation on days 5 to 15, and increased collagen deposition in bladder tissue on day 21 postcystostomy. CONCLUSION: Cystometric evaluation of bladder function in conscious rats is best performed on days 5 to 15 postcystostomy.

Forskolin attenuates the NLRP3 inflammasome activation and IL-1ß secretion in human macrophages.

BACKGROUND: The treatment of nucleotide-binding domain and leucine-rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome-mediated pediatric inflammatory diseases is challenging. Here we studied whether cyclic adenosine monophosphate (cAMP) elevator forskolin could attenuate the nigericin-induced NLRP3-inflammasome activation and interleukin-1ß (IL-1ß) secretion in human macrophages. METHODS: The proteins and messenger RNA (mRNA) levels of inflammasome structural proteins and proinflammatory cytokines were measured in forskolin-stimulated nigericin-activated human THP-1 macrophages and primary macrophages. RESULTS: Activation of THP-1 macrophages with nigericin increased the mRNA expression of NLRP3, IL-1ß, and caspase-1 (P < 0.01). Forskolin stimulation had no effect on the mRNA expression of NLRP3, caspase-1, or IL-1ß in nigericin-activated cells (P > 0.05), while their protein levels were significantly decreased (P < 0.05). Forskolin-mediated increase in cytoplasmic cAMP in non-activated cells was attenuated in nigericin-activated macrophages (P < 0.05). Basal IL-1ß secretion increased from 584 to 2696 pg/mL (P < 0.01) in nigericin-activated macrophages; forskolin dose-dependently reduced the nigericin-induced secretion of mature IL-1ß (P < 0.01). Forskolin also inhibited the IL-1ß secretion from activated human primary macrophages. CONCLUSIONS: Forskolin inhibits the NLRP3 inflammasome activation and the secretion of mature IL-1ß, in human macrophages. Forskolin and other cAMP elevator drugs could represent a novel approach for treatment of diseases associated with excessive inflammasome activation, like pediatric inflammatory diseases.

The influence of delay elimination communication on the prevalence of primary nocturnal enuresis-a survey from Mainland China.

AIMS: A pilot survey shows that primary nocturnal enuresis (PNE) prevalence has increased significantly during the past decade in Mainland China. Whether it is related to the delay of elimination communication (EC) is unclear. This study retrospectively investigated the influence of delayed EC on the PNE prevalence in children and adolescents in mainland China. METHODS: A cross-sectional study of PNE prevalence was performed by distributing 19 500 anonymous self-administered questionnaires to parents in five provinces of mainland China from July 2017 to October 2017. The questionnaires included sociodemographic data, family caregivers' information, and details about the disposable diapers (DD) usage, EC commencement date, psychological disorders, lower urinary tract symptoms, and family history of PNE in children and adolescents. The 2017 PNE prevalence was compared with that of 2006 in Mainland China. RESULTS: The total response rate was 97.04% (18 631 of 19 500) and 92.39% (18 016 of 19 500) qualified for statistical analysis. The PNE prevalence in 2017 has increased significantly compared to that of 2006 (7.30% vs 4.07%, P < 0.001). The PNE prevalence in children with EC starting before 6 months of age was significantly lower than those who start after 12 months of age. The longer DD were used and the later the beginning of EC, the higher the PNE prevalence was found. CONCLUSIONS: The PNE prevalence in Mainland China has increased significantly during the past 10 years. A longer use of DD and later onset of EC may be risk factors for PNE.