Role and significance of SIRT1 in regulating the LPS-activated pyroptosis pathway in children with congenital hydronephrosis

Objective To explore the characteristics and mechanism of sirtuin 1(SIRT1)in lipopolysaccharide(LPS)-activated pyroptosis in the renal tissue of children with congenital hydronephrosis(CHn).Methods We detected the expression characteristics and clinical significance of SIRT1 and pyroptosis pathway proteins in CHn renal tissues by immunohistochemistry.The degree of renal fibrosis was detected by Masson staining.The human renal tubular epithelial cell line(HK-2)was cultured in vitro and treated with LPS(1µg/mL),the SIRT1-specific agonist SRT1720(2.5µmol/L)and small interfering RNA(siRNA)-SIRT1 for 48 hours.After 48 hours,Cell Counting Kit-8 was used to detect the changes in cell proliferation ability,and ELISA was used to detect the changes in the expression of interleukin(IL)-1β and IL-18 in the cell supernatant.Real-time PCR(quantitative RT-PCR)and western blot analysis were used to detect the expression of SIRT1,caspase-1,caspase-4,NOD-like receptor thermal protein domain associated protein 3(NLRP3),and cleaved gasdermin D(GSDMD)in each group.Results Serum inflammatory cytokines were significantly elevated in 13 children with CHn with urinary tract infection,mainly caused by Gram-negative bacteria.Severe renal fibrosis occurred in children with CHn.Compared with the control group,the expression of SIRT1 in CHn kidney tissues was decreased,and the expression of caspase-4 and GSDMD was increased.LPS inhibited the expression of SIRT1 in HK-2 cells,promoted the expression of caspase-1,caspase-4,NLRP3,cleaved GSDMD,promoted the expression of IL-1β and IL-18 in the supernatant,and promoted pyroptosis in HK-2 cells.SRT1720 can inhibit LPS-activated pyroptosis by promoting SIRT1 expression,while siRNA-SIRT1 can further aggravate LPS-activated pyroptosis after inhibiting SIRT1 expression.Conclusions LPS can promote the inflammatory response in children with CHn by activating non-canonical pyroptosis and inhibiting SIRT1 expression.Promoting SIRT1 expression can inhibit pyroptosis of renal tubular epithelial cells,reduce the release of IL-18 and IL-1β,and alleviate the progression of renal fibrosis in children with CHn.

Prevention and control strategies for emergency,limited-term,and elective operations in pediatric surgery during the epidemic period of COVID-19

The outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread to more than 100 countries.Children approved to be susceptible to SARS-CoV-2 infection.Preventing and controlling the epidemic while ensuring orderly flows of pediatric surgery clinical work has proven to be a big challenge for both patients and clinicians during the epidemic.Based on the transmission characteristics of SARS-CoV-2 and the requirements for prevention and control of COVID-19,the authors proposed some concrete measures and practical strategies of managing emergency,limited-term,and elective pediatric surgeries during the epidemic period.

Current treatment for Wilms tumor:COG and SIOP standards

background Wilms tumor(WT)is the most common renal malignant tumor in children.It occurs primarily at preschool age.The purpose of this review is to present current standards of diagnosis and treatment of WT around the world.Data sources All the recent literature on diagnosis and treatment of WT were searched and reviewed.results Most cases with WT are sporadic.The current survival in patients with WT is high(90%).Involvement of mutidisciplinary collaborative groups in the diagnosis and treatment of WT.National Wilms Tumor Study Group(NWTSG)/Children’s Oncology Group(COG)and The International Society of Paediatric Oncology(SIOP)are two major guidelines used for the current management of WT worldwide.The major difference exists in the two guidelines is the timing of surgery:SIOP recommends using preoperative chemotherapy,and NWTSG/COG prefers using primary surgery before any adjuvant treatments.Conclusions Most patients with WT have good overall survival outcomes.Further studies should be highlighted on how to use chemotherapy and radiotherapy under more accurate risk-stratified strategies.Surgeons must be more focusing on how to maximize preoperative and postoperative treatment possibilities for achieving optimal results of patients with WT.

Treatment efficacy of tolterodine versus belladonna mixture in children with idiopathic overactive bladder

Objectives Children with symptoms of urinary urgency,frequency and incontinence are common in the clinic.The aim of the present study was to compare the tolerability and efficacy of tolterodine,a bladder-selective muscarinic receptor antagonist,with belladonna mixture,a traditional anticholinergic drug,in the treatment of idiopathic overactive bladder in children.Methods Children aged 5-10 years with a history of diurnal urgency,frequency and incontinence were randomly divided into two groups.Participants in group 1 were given tolterodine 1 mg twice a day for 14 days.If the results were found to be mildly ineffective,after the first 14 days of therapy,prolonged course with 2 mg twice a day was given.In group 2,the children were treated with belladonna mixture 5 mL twice a day for 14 days.Anticholinergic side effects were recorded during the therapy and efficacy was evaluated with voiding diary recorded by the parents at the beginning and end of therapy.results A total of 668 cases were included in this study and 334 for each 25 group(496 boys and 172 girls).Evident anticholinergic side effects which could cease the therapy,such as dry mouth,constipation,mood changes,irritability,and so on,exhibited only on 2%of participants in the tolterodine group but 69%in the belladonna mixture group(p≤0.05).The symptoms of detrusor overactivity disappeared or significantly improved in 80%of children in the tolterodine group and 37%in the belladonna mixture(p≤0.05)group.Conclusions Tolterodine had better tolerability and efficacy than belladonna mixture in treating overactive bladder in children.