Expert Consensus on Nutritional Support for Children with Congenital Heart Disease(2023 Edition)

The second edition of the expert consensus on pediatric nutrition was formed based on a global update of pedia-tric nutrition guidelines or consensus worldwide,the management of congenital heart disease,and the results of multi-center clinical nutrition research for congenital heart disease following thefirst Chinese consensus edition of 2016.The consensus was also shaped by the results of three discussion sessions and two questionnaires con-ducted by the 13-member collaboration group.This process was informed by both clinical guidelines and expert consensus.The quality of literature,both in English and Chinese,and the level of recommendations were evaluated using the Grading of Recommendations Assessment,Development,and Evaluations(GRADE)system.

Clinical features, endoscopic polypectomy and STK11 gene mutation in a nine-month-old Peutz-Jeghers syndrome Chinese infant

AIM: To investigate multiple polyps in a Chinese PeutzJeghers syndrome(PJS) infant. METHODS: A nine-month-old PJS infant was admitted to our hospital for recurrent prolapsed rectal polyps for one month. The clinical characteristics, a colonoscopic image, the pathological characteristics of the polyps and X-ray images of the intestinal perforation were obtained. Serine threonine-protein kinase 11(STK11) gene analysis was also performed using a DNA sample from this infant.RESULTS: Here we describe the youngest known Chinese infant with PJS. Five polyps, including a giant polyp of approximately 4 cm × 2 cm in size, were removed from the infant's intestine. Laparotomy was performed to repair a perforation caused by pneumoperitoneum. The pathological results showed that this child had PJS. Molecular analysis of the STK11 gene further revealed a novel frameshift mutation(c.64_65het_del AT) in exon 1 in this PJS infant.CONCLUSION: The appropriate treatment method for multiple polyps in an infant must be carefully considered. Our results also show that the STK11 gene mutation is the primary cause of PJS.

Antioxidant drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis:What does evidence suggest?

AIM:To determine whether or not the use of antioxidant supplementation aids in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis.METHODS:A systematic review of randomized controlled trials(RCTs) was made to evaluate the preventive effect of prophylactic antioxidant supplementation in post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP).The inclusion criteria included:acute post-endoscopic retrograde cholangiopancreatography pancreatitis in adults; randomized clinical trials with the use of any antioxidant as an intervention compared with placebo,to reduce PEP.The outcome measure was the incidence and severity of PEP.Twelve RCTs involving 3110 patients since 1999 wereincluded.The antioxidants used were selenite,β-carotene,and pentoxifylline(each one in one trial),N-acetylcysteine(NAC) in three trials,and allopurinol in six trials.The group of patients treated with NAC received different doses; either oral or intravenous,and allopurinol-treated patients received five different oral doses in two different administration periods.The results are expressed with raw numbers,proportions,as well as mean and standard deviations.The incidence of pancreatitis between groups was analyzed with Pearson's χ2 test or Fisher's exact test(F).The main outcome is expressed as relative risks and 95%CI.RESULTS:The incidence of pancreatitis in all antioxidant treatment groups was 8.6%,whereas it was 9.7% in the control group.The antioxidants used were selenite,β-carotene,and pentoxifylline(each one in one trial),NAC in three trials,and allopurinol in six trials.In allopurinol trials,three different dosifications were used; two trials reported a low dosage(of less than 400 mg),two trials reported a moderate dose(600 mg) and the remaining two employed higher doses(more than 900 mg).Supplementation was not associated with a significant reduction in the incidence of PEP [relative risk(RR) = 0.93; 95%CI:0.82-1.06; P = 0.28].In addition,the incidences of PEP in patients treated with allopurinol and those treated with other antioxidants were similar to that observed in patients who received the placebo(RR for trials with allopurinol,0.92; 95%CI:0.78-1.08; P = 0.31) and,with the use of other antioxidants,the incidence of PEP was 8.9%,whereas it was 9.7% in the control group(RR = 0.95; 95%CI:0.77-1.18; P = 0.19).CONCLUSION:Antioxidant supplementation shows no beneficial effect on the incidence of PEP.There is a lack of robust trials to support the use of antioxidants for prevention.

Neonatal biliary atresia combined with preduodenal portal vein:A case report

BACKGROUND Congenital biliary atresia is a type of obstruction of the bile ducts inside and outside the liver,which can lead to cholestatic liver cirrhosis and eventually liver failure.The preduodenal portal vein(PD-PV)is a rare developmental malformation of the PV.The PV courses in front of the duodenum.However,very few cases of neonatal biliary atresia combined with PD-PV have been reported in the scientific literature.CASE SUMMARY A 1-mo-and-4-d-old child was admitted to the hospital in January because of yellowish skin.After surgical consultation,surgical intervention was recommended.The child underwent Hilar-jejunal anastomosis,duodenal rhomboid anastomosis,and abdominal drainage under general anesthesia.During the operation,the PV was located at the anterior edge of the duodenum.CONCLUSION Diagnoses:(1)Congenital biliary atresia;(2)PD-PV;and(3)Congenital cardiovascular malformations.Outcomes:Recommendation for liver transplantation.Lessons:The choice of treatment options for neonatal biliary atresia combined with PD-PV.

Congenital hepatic cyst:Eleven case reports

BACKGROUND Liver cysts in infants are uncommon.With modern diagnostic imaging,we can achieve an early diagnosis of congenital hepatic cysts.Our purpose was to investigate the clinical features,surgical treatment methods and prognosis of infants with congenital hepatic cysts.Herein,we report a case series of congenital hepatic cysts.CASE SUMMARY Eleven infants with hepatic cysts were retrospectively analysed.Ten of them had simple hepatic cysts,and a girl with a large hepatic mass was diagnosed with a solitary intrahepatic biliary cyst accompanied by a choledochal cyst.Among the ten simple hepatic cysts,eight were solitary and two were multiple.A total of 87.5%(7 of 8)of infants with solitary hepatic cysts were detected before delivery,and 86%(6 of 7)of those cysts were located in the right lobe of the liver.Surgical intervention was required for symptomatic hepatic cysts.Cyst resection or unroofing with fulguration of the cyst bed was employed.No recurrence of cysts was observed in these infants.CONCLUSION Congenital hepatic cyst is a condition with a narrow differential diagnosis.Accurate diagnosis is essential for appropriate management.Unroofing is the favoured treatment in infants with symptomatic cysts.Most infants with congenital hepatic cysts have a good prognosis.

Unusual presentation of bladder neuroblastoma in a child: A case report

BACKGROUND Neuroblastoma is an extracranial malignant tumor in children that is most often located in the adrenal gland and sympathetic ganglion.Here,we present a rare case of neuroblastoma originating from the urinary bladder.CASE SUMMARY A 3-year-old girl presented with lower abdominal pain with micturition.Ultrasound revealed a lower abdominal mass.Abdominal computed tomography scan displayed a solitary mass at the top of the urinary bladder.Blood levels of neuron-specific enolase and lactate dehydrogenase were elevated.We treated the child with partial cystectomy and six courses of chemotherapy,and the outcome at 4-year follow-up was unremarkable.CONCLUSION Neuroblastoma should be considered when tumors are located in the urinary bladder,especially in the dome;although this presentation is rare,the prognosis is very good.

Upregulation of MEG3 inhibits neuroblastoma progression via decreasing proliferation and promoting apoptosis

Background:We have shown that downregulation of materally expressed gene 3(MEG3)promoted autophagy and epithelial-mesenchymal transition to promote neuroblastoma(NB)progression.In present study,we aim to further discover the role of MEG3 in NB.Methods:Expression levels of MEG3 in stabled transfected cells were detected by qPCR.Flow cytometry was used to examine the effects of MEG3 overexpression on apoptosis and cell cycle.Moreover,tumor stemness was detected by tumor sphere formation assay.Results:QPCR showed that MEG3 was successfully overexpressed in SK-N-BE(2)C and SK-N-AS cells.CCK8 indicated MEG3 reduced cell proliferation in two NB cells.Flow cytometry revealed that MEG3 promoted apoptosis and caused G0/G1 arrest.Using chromatin isolation by RNA purification(ChIRP)and tumor sphere formation assays,we revealed that upregulation of MEG3 decreased tumor stemness by decreasing Nestin transcription.Conclusions:Overall,present study confirmed an anti-cancer role of MEG3 in NB,demonstrated that MEG3 could be a potential therapeutic target of NB.

Sclerosing angiomatoid nodular transformation of the spleen in children:a two-case report of laparoscopic total or partial splenectomy and a literature review

Sclerosing angiomatoid nodular transfor-mation(SANT)is a rare splenic lesion first described by Martel et al in 2004.^(1)As reported,SANT is a benign vascular lesion of the red pulp of the spleen,presenting under the microscope as angiomatoid nodules in a fibrosclerotic stroma.

Mechanism of Endogenous Peptide PDYBX1 and Precursor Protein YBX1 in Hirschsprung’s Disease

Endogenous peptides,bioactive agents with a small molecular weight and outstanding absorbability,regulate various cellular processes and diseases.However,their role in the occurrence of Hirschsprung’s disease(HSCR)remains unclear.Here,we found that the expression of an endogenous peptide derived from YBX1(termed PDYBX1 in this study)was upregulated in the aganglionic colonic tissue of HSCR patients,whereas its precursor protein YBX1 was downregulated.As shown by Transwell and cytoskeleton staining assays,silencing YBX1 inhibited the migration of enteric neural cells,and this effect was partially reversed after treatment with PDYBX1.Moreover,immunoprecipitation and immunofluorescence revealed that ERK2 bound to YBX1 and PDYBX1.Downregulation of YBX1 blocked the ERK1/2 pathway,but upregulation of PDYBX1 counteracted this effect by binding to ERK2,thereby promoting cell migration and proliferation.Taken together,the endogenous peptide PDYBX1 may partially alleviate the inhibition of the ERK1/2 pathway caused by the downregulation of its precursor protein YBX1 to antagonize the impairment of enteric neural cells.PDYBX1 may be exploited to design a novel potential therapeutic agent for HSCR.

Progress in Biomarkers Related to Biliary Atresia

Biliary atresia(BA)is a congenital cholestatic disease that can seriously damage children’s liver function.It is one of the main reasons for liver transplantation in children.Early diagnosis of BA is crucial to the prognosis of patients,but there is still a lack of reliable non-invasive diagnostic methods.Additionally,as some children are in urgent need of liver transplantation,evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward,efficient,and less traumatic method is a major focus of doctors.In recent years,an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice:diagnosis,evaluation of the stage of liver fibrosis,and prediction of native liver survival.This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers,namely MMP-7,FGF-19,and M2BPGi.Furthermore,progress in well-known biomarkers of BA such as gamma-glutamyltransferase,circulating cytokines,and other potential biomarkers is discussed,aiming to provide a reference for clinical practice.

All-trans retinoic acid inhibits the malignant behaviors of hepatocarcinoma cells by regulating ferroptosis

All-trans retinoic acid(ATRA)can reverse the malignant behaviors of hepatocellular carcinoma(HCC)cells,thereby exerting anti-HCC effect;however,the underlying mechanism is yet to be understood.This study aimed to demonstrate that ATRA is vital to ferroptosis in HCC.Ferroptosis-related genes exhibit different expression in patients with HCC compared to that in healthy individuals.A total of 20 amino acid products were detected in HepG2 cells,the expression level of 5 was decreased after ATRA treatment.ATRA improved the levels of lipid ROS,MDA,and NAPDt/NADPH,and reduced the mt-DNA copy number and changed the structure of mitochondria,in HepG2 and Hep3B cells.We found the expression of genes positively correlated with ferroptosis to increase and those negatively correlated to decrease with ATRA treatment.Inhibition of ferroptosis by Ferrostatin-1 reversed ATRA-inhibited proliferation of HCC cells,along with cell migration and invasion.GSH synthesis was blocked by ATRA,accompanied by decreased cystine content and increased glutamate content,and downregulation of the expression of GSH synthesis-related genes.Our findings suggested that ATRA inhibited the malignancy of HCC cells by improving ferroptosis,and that inhibition of GSH synthesis contributed to ATRA-induced ferroptosis.

Standards of care for Kasabach-Merritt phenomenon in China

Kasabach-Merritt phenomenon(KMP)is a rare disease that is characterized by severe thrombocytopenia and consumptive coagulation dysfunction caused by kaposiform hemangioendothelioma or tufted hemangioma.This condition primarily occurs in infants and young children,usually with acute onset and rapid progression.This review article introduced standardized recommendations for the pathogenesis,clinical manifestation,diagnostic methods and treatment process of KMP in China,which can be used as a reference for clinical practice.

The contribution of proteoglycans to heterogeneity and temozolomide resistance of glioblastoma cells

Aim:Heterogeneity of glioblastoma(GB)cells significantly contributes to tumor resistance against temozolomide(TMZ)and the development of disease relapse.Multiple molecular mechanisms are involved in this process,yet the contribution of proteoglycans(PGs)remains unknown.This study aimed to investigate the potential involvement of PGs(both at core proteins and polysaccharide chains)in the heterogeneity and TMZ resistance of GB cells.Methods:Seven human GB cell lines were characterized for TMZ sensitivity,cell phenotypic traits,gene expression for glucocorticoid receptor(GR,NR3C1),PG core proteins-and heparan sulfate(HS)biosynthesis-related genes and content of their chondroitin sulfate(CS)and HS chains.Results:Although the studied cell lines have similar proliferation rates,they significantly differ in their migration activity,clonogenicity,and TMZ resistance(IC508.51-369.59µM in the line of U343,LN215,HS683,U87,LN71,LN405,LN18),creating a specific phenotype for each cell line.Some PGs(NG2/CSPG4,CSPG5,and versican)contributed to the molecular heterogeneity of these cells being cell line-specifically expressed in all cell lines,which also differed in terms of the CS/HS content.Transcriptional activity of the HS metabolic system was low in these GB cell lines,expressing mainly EXT1/2 and NDST1/2,while expression levels of sulfotransferases and SULF2 were cell line-specific.TMZ resistance of these cells was correlated with the expression of stem-cell marker CD44(+3.5-fold,r=0.73)and GR(-3-fold,r=-0.81).TMZ treatment of the resistant(LN405)and sensitive(LN215)cells resulted in complex changes in cell migration as well as NG2/CSPG4 expression and CS/HS content.Conclusion:Differential expression of PGs and CS/HS content contribute to the heterogeneity of GB cells,and CD44 and NR3C1 might be informative biomarkers for TMZ resistance.

miR-181b-5p/SOCS2/JAK2/STAT5 axis facilitates the metastasis of hepatoblastoma

Introduction:Hepatoblastoma(HB)is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected patients.The precise molecular mechanisms responsible for HB metastasis remain incom-pletely understood.However,there is evidence suggesting a connection between the dysregulation of microRNAs(miRNAs)and the progression of tumor metastasis in HB.Methods:The study utilized weighted gene co-expression network analysis(WGCNA)to analyze a miRNA microarray dataset of HB.The expression of miR-181b-5p in HB tissues and cells was detected using quantitative real-time PCR.The impact of miR-181b-5p on the metastatic capacity of HB was evaluated through scratch and Transwell assays.The effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated in vivo.Furthermore,a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in HB.Results:We found that miR-181b-5p was highly expressed in HB tissues and HB cell lines.Overexpression of miR-181b enhanced scratch healing,cell migration,and invasion abilities in vitro,as well as enhancing HB lung metastasis potential in vivo.Dual-luciferase reporter assays showed that Suppressor Of Cytokine Signaling 2(SOCS2)was a direct target of miR-181b.The overexpression of miR-181b resulted in the suppression of SOCS2 expression,subsequently activating the epithelial-mesenchymal transition and JAK2/STAT5 signaling pathways.The rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB cells.Conclusion:Our study showed that miR-181b promotes HB metastasis by targeting SOCS2 and may be a potential therapeutic target for HB.

VEGFA rs3025039 and biliary atresia susceptibility in Chinese population:a systematic review and meta-analysis

Background Previous studies have suggested an association between vascular endothelial growth factor A(VEGFA)rs3025039 polymorphism and biliary atresia(BA).However,this conclusion is controversial and there is no published pooled evidence of this association.Methods This study was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.The protocol was registered with PROSPERO(International Prospective Register of Systematic Reviews).A thorough search was performed on databases including PubMed,Embase,and Chinese Biomedical Database up to August 2020.This study included 846 cases of BA and 2821 controls concerning VEGFA rs3025039 polymorphism.We selected relevant studies based on the following inclusion criteria:(1)the study design was case-control and cohort and(2)the patients carried standard clinical diagnoses of BA,etc.The exclusion criteria were as follows:(1)patients with other related diseases,(2)lack of requisite information and(3)duplicate data.The OR(odd ratio)and the corresponding 95%CI(confidence interval)were calculated to estimate the association.Results This study on VEGFA rs3025039 polymorphism in the Chinese population included 846 cases and 2821 controls.The results showed that there was no significant association between rs3025039 and susceptibility to BA under four genetic models.The results of the subgroup analysis were similar to the overall results.Conclusions This meta-analysis shows that rs3025039 was not associated with susceptibility to BA in the Chinese population.Further validation may entail additional research.PROSPERO registration number CRD42020203812.

Super-enhancer-associated TTC8 alters the nucleocytoplasmic distribution of PHOX2B and activates MAPK signaling in neuroblastoma

Super-enhancers are regions of the mammalian genome comprising multiple enhancers in close proximity and often enriched at cancer genes.^(1)Recent studies suggest the emerging roles of super-enhancer-associated genes in un-derlying the cell identity of neuroblastoma(NB)2 which rises from neural crest-derived cells and is one of the most common malignant solid tumors in children.