Mechanosensitive Piezo1 channels promote neurogenic bladder fibrosis via regulating TGF-ß1/smad and Hippo/YAP1 pathways.

Bladder fibrosis is the final common pathway of neurogenic bladder (NB), and its underlying mechanisms are not fully understood. The current study aims to evaluate the involvement of Piezo1, a mechanosensitive channel, in bladder fibrosis. A full-thickness bladder specimen was taken during ileocystoplasty or ureteral reimplantation from the surgical cut's edge. By chopping off the bilateral lumbar 6 (L6) and sacral 1 (S1) spinal nerves, NB rat models were produced. Utilizing both pharmacological inhibition and Piezo1 deletion, the function of Piezo1 in the TGF-ß1-induced fibrosis model of SV-HUC-1 cells was delineated. RNA-seq, immunofluorescence, immunohistochemistry (IHC), and Western blotting were used to evaluate the degrees of fibrosis and biochemical signaling pathways. Piezo1 protein expression was noticeably elevated in the human NB bladder. The abundance of Piezo1 protein in bladder of NB rats was significantly increased. RNA-seq analysis revealed that the ECM-receptor interaction signaling pathway and collagen-containing ECM were increased in spinal cord injury (SCI)-induced bladder fibrosis. Moreover, the bladder of the NB rat model showed activation of YAP1 and TGF-ß1/Smad. In SV-HUC-1 cells, siRNA suppression of Piezo1 led to profibrotic responses and activation of the TGF-ß1/Smad pathway. However, Yoda1, a Piezo1-specific agonist, significantly reduced these effects. TGF-ß1 increased Piezo1 activation and profibrotic responses in SV-HUC-1 cells. In the TGF-ß1-induced fibrosis model of SV-HUC-1 cells, the TGF-ß1/Smad pathway was activated, whereas the Hippo/YAP1 signal pathway was blocked. Inhibition of Piezo1 further prevented this process. Piezo1 is involved in the progression of NB bladder fibrosis and profibrotic alterations in SV-HUC-1 cells, likely through regulating the TGF-ß1/Smad and Hippo/YAP1 pathways.

Clinical Features and Survival Outcomes in Children and Adolescents With Malignant Mediastinal Germ Cell Tumors Based on Surveillance, Epidemiology, and End Results Database Analysis.

INTRODUCTION: The purpose of this study was to perform a population-based investigation to assess the disease characteristics and prognosis of children and adolescents with malignant mediastinal germ cell tumors (MMGCT). METHODS: Data on the demographics, treatment, and survival outcomes of children and adolescents with MMGCT from January 1, 2000 to December 31, 2018 were obtained. To compare survival curves, the log-rank test was employed. The generation of survival curves based on different parameters was done using Kaplan-Meier estimations. Cox proportional hazards regression was performed to determine the variables linked to disease-specific survival. RESULTS: The selection criteria were met by 152 MMGCT patients, 130 of whom were male. Fifty three cases of mixed germ cell tumors (GCTs), 41 cases of malignant teratomas, 26 cases of yolk sac tumors, 14 cases of seminoma, 13 cases of choriocarcinomas, and five cases of embryonal carcinoma were reported. Overall survival at 3 and 5 y for all patients was 63.1% and 61.2%, respectively. Malignant teratoma, yolk sac tumors, and mixed GCTs in children and adolescents had comparable survival rates, while those with choriocarcinoma and embryonal carcinoma showed the worst prognosis. Embryonal carcinoma, malignant teratoma, mixed GCTs, and choriocarcinoma were found as risk factors by multivariate Cox proportional hazards analysis. In contrast, surgery and younger age were protective factors. However, chemotherapy alone showed no survival benefits. CONCLUSIONS: Our population-based evidence showed that MMGCT had worse prognosis in older children and adolescents. Choriocarcinomas and embryonal carcinomas had the worst prognosis. Surgery can prolong survival time. Chemotherapy and radiotherapy were not associated with improved prognosis.

Single-incision versus conventional laparoscopic pyloromyotomy for pediatric hypertrophic pyloric stenosis: a systematic review and meta-analysis.

PURPOSE: To assess the safety and efficacy of single-incision versus conventional laparoscopic pyloromyotomy in pediatrics, we conducted a systematic review and meta-analysis. METHODS: A literature search was conducted to identify studies that compared single-incision laparoscopic pyloromyotomy (SILP) and conventional laparoscopic pyloromyotomy (CLP) for infants with hypertrophic pyloric stenosis (HPS). Meta-analysis was used to pool and compare variables such as operative time, time to full feeding, length of hospital stay, mucosal perforation, inadequate pyloromyotomy, wound infection, incisional hernia and overall complications. RESULTS: Among the 490 infants with HPS in the seven studies, 205 received SILP and 285 received CLP. There was significant longer time to full feeding for SILP compared with CLP. However, pooling the results for SILP and CLP revealed no significant difference in operative time, length of hospital stay and postoperative complications. CONCLUSIONS: SILP is a safe, feasible and effective surgical procedure for infants with HPS when compared to CLP. SILP is equivalent to CLP in terms of operative time, length of hospital stay and postoperative complications. We conclude that LS should be considered an acceptable option for HPS.

Deciphering the point source carbon footprint puzzle: Land use dynamics and socio-economic drivers.

Point source carbon emissions account for approximately 80 % of total emissions. Investigating the influence of land use and socio-economic indicators on these emissions is crucial for achieving sustainable development goals. Existing research faces challenges such as focusing on specific regions, mixing variables that may exhibit multicollinearity, and lacking sufficient land use information. This study takes China, the largest emitting country, as a case study, utilizing geospatial big data to subdivide land use into 11 categories based on emission sectors. The impacts of land use and socio-economic indicators on different emission sectors are discussed from the perspectives of bivariate and spatial statistical analysis, with spatial hotspots identified. Hierarchical regression is used to evaluate the explanatory power of the indicators and to establish models, and potential carbon reduction strategies are further explored. Key findings reveal: (1) Significant multicollinearity between land use and socio-economic indicators was demonstrated, with land use explaining 57.1 % of emissions compared to 37.4 % explained by socio-economic indicators. The spatial consistency between land use and emissions exceeds 80 %, and the spatiotemporal variability is relatively low, making land use a more advantageous factor in explaining point source carbon emissions. (2) Agricultural mechanization increases emission intensity, but this efficient farming method helps convert surplus plowland, the largest influencing factor (Coefficient = 0.717), into carbon sinks, thereby controlling agricultural emissions. (3) Land intensification helps control industrial land, the main factor influencing industrial emissions (Coefficient = 0.392). It also contributes to the efficient use of carbon reduction technologies and industrial supporting land. (4) Mixed commercial and residential land has the greatest impact on commercial, service, and household emissions. However, its relationship with the economy (Correlation = 0.479) is stronger than its relationship with emissions (Correlation = 0.182), making it more applicable to cities that serve as economic growth hubs.

Folic acid supplementation rescues bladder injury in fetal rats with myelomeningocele.

BACKGROUND: Bladder dysfunction has been linked to the progression of renal failure in children with neurogenic bladder (NB) dysfunction. The purpose of this study was to determine whether bladder injuries in fetal rats with myelomeningocele (MMC) may be treated with folic acid. METHODS: Pregnant Sprague-Dawley rats were randomly divided into three groups. On the 10th day of gestation, pregnant rats were intragastrically injected with all-trans retinoic acid (ATRA) (60 mg/kg) to induce MMC fetal rats. The same amount of olive oil was put into the control group to create normal fetal rats. The rats in the rescue group were given folic acid (40 mg/kg) by gavage 0.5 and 12 hr after ATRA therapy. Bladders were obtained via cesarean section on embryonic day E20.5 and examined for MMC. The histology of the fetuses was examined using hematoxylin and eosin staining, and immunohistochemistry (IHC) was utilized to determine the expression of α-smooth muscle actin (α-SMA) and neuron-specific nuclear-binding protein (NeuN). Furthermore, the levels of neuromuscular development-related and apoptotic proteins were determined by western blotting. RESULTS: The incidence of MMC in the model group was 60.6% (20/33) while it was much lower in the rescue group (21.4%). In comparison to the model group, the weight and crown-rump length of the fetal rats in the rescue group were significantly improved. IHC revealed that there was no significant difference in the expression of α-SMA and NeuN between the control and ATRA groups, while the expression levels decreased significantly in the MMC group. Western blot analysis showed that there was no significant difference between the model and ATRA groups, but the expression of the α-SMA protein and the ß3-tubulin was much lower in the MMC group than in the control group. After the administration of folic acid, the α-SMA and ß3-tubulin proteins considerably increased in the folic acid-rescued MMC group and folic acid-rescued ATRA group. Meanwhile, in the control group, the expression of cleaved caspase-3 in the bladder tissue was significantly higher, and the expression of poly (ADP-ribose) polymerase (PARP) protein was significantly lower compared to the control group. Folic acid therapy reduced cleaved caspase-3 expression while increasing PARP expression in comparison to the MMC group. CONCLUSIONS: NB in MMC fetal rats is associated with the reduction of bladder nerve and smooth muscle-related protein synthesis. However, folic acid therapy can help improve these functional deficiencies. Folic acid also exhibits strong anti-apoptotic properties against NB in MMC fetal rats.

Minimally Invasive versus Open Ureteral Reimplantation in Children: A Systematic Review and Meta-Analysis.

PURPOSE: We performed a systematic review and meta-analysis to compare the safety and efficacy of minimally invasive surgery (MIS) versus open ureteral reimplantation (OUR) in children. METHODS: Literature searches were conducted to identify studies that compared MIS (laparoscopic ureteral reimplantation or robot-assisted laparoscopic ureteral replantation) and OUR in children. Parameters such as operative time, blood loss, length of hospital stay, success rate, postoperative urinary tract infection (UTI), urinary retention, postoperative hematuria, wound infection, and overall postoperative complications were pooled and compared by meta-analysis. RESULTS: Among the 7,882 pediatric participants in the 14 studies, 852 received MIS, and 7,030 received OUR. When compared with the OUR, the MIS approach resulted in shorter hospital stays (I 2 = 99%, weighted mean difference [WMD] -2.82, 95% confidence interval [CI] -4.22 to -1.41; p < 0.001), less blood loss (I 2 = 100%, WMD -12.65, 95% CI -24.82 to -0.48; p = 0.04), and less wound infection (I 2 = 0%, odds ratio 0.23, 95% CI 0.06-0.78; p = 0.02). However, no significant difference was found in operative time and secondary outcomes such as postoperative UTI, urinary retention, postoperative hematuria, and overall postoperative complications. CONCLUSION: MIS is a safe, feasible, and effective surgical procedure in children when compared with OUR. Compared with OUR, MIS has a shorter hospital stay, less blood loss, and less wound infection. Furthermore, MIS is equivalent to OUR in terms of success rate and secondary outcomes such as postoperative UTI, urinary retention, postoperative hematuria, and overall postoperative complications. We conclude that MIS should be considered an acceptable option for pediatric ureteral reimplantation.

Survival and Analysis of Prognostic Factors for Bladder Malignancies in Children and Adolescents: A Population-based Study.

OBJECTIVE: To explore the clinicopathological features and prognosis of pediatric patients with malignant bladder tumors in a population-based cohort. METHODS: The database Surveillance, Epidemiology, and End Results was used to evaluate all pediatric patients diagnosed with malignant bladder tumors between 1975 and 2018. The log-rank test was used to compare survival curves. Kaplan-Meier estimations were used to create survival curves based on various parameters. The Cox proportional hazards model was utilized to determine the factors that were independently related to mortality. RESULTS: A total of 263 children and adolescents with bladder malignancies were assessed. Papillary urothelial neoplasms of low malignant potential were the most frequent histologic subtype (35.1%), while embryonal rhabdomyosarcoma was more common during the first decade of life. Survival rates varied significantly by age at diagnosis, with older patients showing better outcomes. When compared to other subtypes, papillary urothelial neoplasms of low malignant potential had the highest overall survival rates (3- and 5-year were 99.2% and 98.3%, respectively). Multivariate analysis of the entire cohort showed that Surveillance, Epidemiology, and End Results stage and surgery were significant independent predictors of progression to disease-specific death in this model. CONCLUSION: Bladder malignancies are rare in children and adolescents. The prognosis for them varies. The localized stage was independently associated with superior survival and surgery could extend survival time.