Effect of Kasai procedure on liver transplantation in children with biliary atresia: a systematic review and updated meta-analysis.

Background: Kasai procedure and liver transplantation are effective ways to save the life of children with biliary atresia (BA). However, with the gradual development of liver transplantation technology, scholars have questioned the necessity of the Kasai procedure. Therefore, we conducted a meta-analysis to evaluate the effect of previous Kasai procedures on liver transplantation in children with BA. Methods: Seven databases were searched and screened from the establishment of the database to May 3, 2023. The data in the included literature were extracted for meta-analysis to compare the differences between the Kasai group and the non-Kasai group. Finally, a publication bias test, sensitivity analysis, subgroup analysis, and systematic review were performed. Results: A total of 26 studies were included in which 6,522 children with BA underwent liver transplantation, including 4,989 in the Kasai group. Compared with the non-Kasai group, the Kasai group had older age [standardized mean difference (SMD) =0.64; 95% confidence interval (CI): 0.46, 0.82; P<0.001] (I2=78.6%), heavier weight (SMD =0.41; 95% CI: 0.33, 0.48; P<0.001) (after sensitivity analysis, I2=0.0%), lower pediatric end-stage liver disease (PELD) (SMD =-0.41; 95% CI: -0.48, -0.35; P<0.001) (I2=20.1%), longer operation time (SMD =0.33; 95% CI: 0.01, 0.65; P<0.001) (I2=83.2%), more intraoperative blood loss (SMD =0.26; 95% CI: 0.06, 0.46; P=0.012) (I2=19.1%), shorter intensive care unit (ICU) stay (SMD =-0.09; 95% CI: -0.34, 0.15; P=0.027) (I2=68.6%) and higher incidence of intestinal perforation [odds ratio (OR) =1.96; 95% CI: 1.20, 3.18; P=0.007] (I2=7.4%) and biliary complications (OR =1.41; 95% CI: 1.05, 1.89; P=0.024) (I2=31.4%). In the "Asia" subgroup, the Kasai group was older (SMD =0.68; 95% CI: 0.52, 0.84; P<0.001) (I2=28.2%). In the "Cases since 2000" subgroup, there was no significant difference in operation time between the two groups (I2=28.5%). In the "Other" and the "non-Asia" subgroup, there was no significant difference in length of intensive care unit (ICU) stay between the two groups (I2=0.0%). However, there were no significant differences in other postoperative complications and prognostic indicators between the two groups. Conclusions: For children with BA undergoing liver transplantation, although previous Kasai procedure may increase the risk of intraoperative bleeding, biliary complications, and intestinal perforation, it does not affect the main clinical outcomes, and can even delay the timing of liver transplantation and improve the preoperative status of children. Therefore, when BA children have no obvious contraindications to Kasai procedure, the sequential treatment of Kasai procedure-liver transplantation should be supported first.

Biliary atresia: the development, pathological features, and classification of the bile duct.

Biliary atresia is an occlusive biliary disease involving intrahepatic and extrahepatic bile ducts. Its etiology and pathogenesis are unclear. There are many manifestations of bile duct involvement in biliary atresia, but little is known about its occurrence and development. In addition, different classification methods have been proposed in different periods of biliary atresia, each with its advantages and disadvantages. The combined application of biliary atresia classification will help to improve the survival rate of patients with native liver. Therefore, this article reviews the development, pathological features, and classification of intrahepatic and extrahepatic bile ducts in biliary atresia, to provide a reference for the study of the pathogenesis and the choice of treatment methods.

Diagnostic and prognostic value of the gut microbiota and its metabolite butyrate in children with biliary atresia.

PURPOSE: To determine the prevalent microbiological profile of biliary atresia (BA) patients at the time of its occurrence by studying their intestinal flora. METHODS: A total of 118 gut microbiota samples from three groups of 43 BA patients, 33 disease controls (DC) with other cholestatic diseases and 42 healthy controls (HC), were analyzed by deep mining of public data. Subsequently, a total of 23 fecal samples from three groups of clinically collected patients (11 BA, 6 DC and 6 HC) were sequenced for 16S rRNA gene amplification and analyzed for serum butyrate (BU) level by liquid chromatography. RESULTS: Taxonomic analysis revealed significant differences in the composition of the intestinal microbiota between BA patients and controls, with a reduction in diversity and a higher abundance of Proteobacteria, Streptococcus and Lactobacillus in the BA group. Database and clinical data analyses concluded that Streptococcus/Bacteroides (AUC = 0.9035, 95% CI 0.8347-0.9722, P < 0.0001) or Streptococcus/Eggerthella (AUC = 0.8333, 95% CI 0.6340-1.000, P = 0.027) was the best microbiota to differentiate between BA and DC. Serum butyrate levels were low in the BA and DC groups and differed from the HC group (P = 0.01, P = 0.04). Butyrate levels in BA were negatively correlated with jaundice clearance and cholangitis, but not statistically significant. CONCLUSIONS: Our study reveals changes in the composition of the gut microbiota in BA, especially the butyrate-producing microbiota, and suggests the potential for using gut microbiota as a noninvasive diagnostic benefit for BA. Low levels of serum butyrate in BA may indicate a poor prognosis.

Effects of respiratory flora regulation on microbial environment and IL-10/STAT3 signaling pathway in the bronchiolitis obliterans after lung transplantation.

Our purpose of this study was to explore the application effect of respiratory flora regulation in bronchiolitis obliterans after lung transplantation, and its regulatory effect on the microbial environment of the lesion and the IL-10/STAT3 signaling pathway. 25 clean-grade C57BL/6 male mice and 5 BALB/c male mice were selected for orthotopic tracheal transplantation and postoperative respiratory flora regulation in a hospital animal room from Jan 2019 to Dec 2021. Next, the changes in the microbial environment and the IL-10/STAT3 signaling pathway before and after respiratory flora regulation were compared, so as to evaluate the regulatory effect of this method. The Simpson index did not show a significant difference before and after respiratory flora regulation intervention (P>0.05). However, the Chao1, ACE, Shannon, and Actinobacteria dominant indices were higher after the intervention. There were significant changes in the abundance of Proteobacteria, Bacteroidetes, Acidobacteria, Firmicutes, Propionibacterium, Corynebacterium, Staphylococcus, and Streptococcus after the intervention (P<0.05). Additionally, IL-10 and STAT3 levels were higher after the intervention and showed significant differences (P<0.05) compared to before. Regulating the respiratory tract flora can improve the microbial environment of bronchiolitis obliterans post-lung transplantation. This helps balance the respiratory flora, increase IL-10 and STAT3 levels, and aid in the recovery of inflammatory responses.

Development and post-Kasai procedure prognostic relevance of histological features for biliary atresia.

OBJECTIVES: To validate an appropriate evaluation method of liver fibrosis assessment based on the unique pathological features of biliary atresia (BA) that could well predict its prognosis. METHODS: A total of 68 patients with BA who underwent Kasai procedure (KP) and an intraoperative liver biopsy, followed up from January 2019 to December 2021, were recruited in a retrospective analysis. Ishak, Metavir, and BA-specific staging systems in relation to outcomes were analyzed using logistic regression, COX proportional hazard regression, Kaplan-Meier analysis, etc. RESULTS: Kaplan-Meier analysis determined a significant difference in native liver survival according to the BA-specific stage (p = 0.002). The ROC curve analysis for predicting prognosis showed that the AUC of BA-specific staging combined with iBALF and severe bile duct proliferation (BDP) (0.811, 95% CI: 0.710-0.913, p < 0.0001) was higher than BA-specific staging alone (0.755, 95% CI: 0.639-0.872, p < 0.001). CONCLUSIONS: The BA-specific staging system reflects the condition of the liver fibrosis, and its combination with iBALF and severe BDP helps to better evaluate the prognosis of patients with BA.

Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China.

BACKGROUND: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. RESULTS: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. CONCLUSIONS: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.

Potential therapeutic target of EGF on bile duct ligation model and biliary atresia children.

BACKGROUND: The pathogenesis of liver fibrosis in biliary atresia (BA) is unclear. Epidermal growth factor (EGF) plays a vital role in liver fibrosis. This study aims to investigate the expression of EGF and the mechanisms of its pro-fibrotic effects in BA. METHODS: EGF levels in serum and liver samples of BA and non-BA children were detected. Marker proteins of EGF signaling and epithelial-mesenchymal transition (EMT) in liver sections were evaluated. Effects of EGF on intrahepatic cells and the underlying mechanisms were explored in vitro. Bile duct ligation (BDL) mice with/without EGF antibody injection were used to verify the effects of EGF on liver fibrosis. RESULTS: Serum levels and liver expression of EGF elevated in BA. Phosphorylated EGF receptor (p-EGFR) and extracellular regulated kinase 1/2 (p-ERK1/2) increased. In addition, EMT and proliferation of biliary epithelial cells were present in BA liver. In vitro, EGF induced EMT and proliferation of HIBEpic cells and promoted IL-8 expression in L-02 cells by phosphorylating ERK1/2. And EGF activated LX-2 cells. Furthermore, EGF antibody injection reduced p-ERK1/2 levels and alleviated liver fibrosis in BDL mice. CONCLUSION: EGF is overexpressed in BA. It aggravates liver fibrosis through EGF/EGFR-ERK1/2 pathway, which may be a therapeutic target for BA. IMPACT: The exact pathogenesis of liver fibrosis in BA is unknown, severely limiting the advancement of BA treatment strategies. This study revealed that serum and liver tissue levels of EGF were increased in BA, and its expression in liver tissues was correlated with the degree of liver fibrosis. EGF may promote EMT and proliferation of biliary epithelial cells and induce IL-8 overexpression in hepatocytes through EGF/EGFR-ERK1/2 signaling pathway. EGF can also activate HSCs in vitro. The EGF/EGFR-ERK1/2 pathway may be a potential therapeutic target for BA.

The correlation between rs2501577 gene polymorphism and biliary atresia: a systematic review and meta-analysis.

IMPORTANCE: Multiple studies indicate a possible correlation between ADD3 rs2501577 and biliary atresia susceptibility; however, a conclusive determination has yet to be made. OBJECTIVE: Investigate the role of ADD3 rs2501577 in biliary atresia susceptibility across diverse populations. DATA SOURCES: The study protocol has been registered on PROSPERO, an international platform for systematic review registration (PROSPERO ID: CRD42023384641). The following databases will be searched until February 1, 2023: PubMed, Embase, Cochrane, CBM, Web of Science, and CNKI. STUDY SELECTION: Eight studies were selected from seven papers to assess the data. A total of 7651 participants were included, consisting of 1662 in the BA group and 5989 in the NC group. DATA EXTRACTION AND SYNTHESIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed while conducting the systematic reviews and meta-analyses. Two authors independently assessed the quality of the included studies using the Newcastle-Ottawa Quality Assessment Scale. The significance of the pooled odds ratio (OR) was evaluated with a Z test, and statistical heterogeneity across studies was assessed using the I2 and Q statistics. Publication bias was assessed using Egger's and Begg's tests. MAIN OUTCOME(S) AND MEASURE(S): The primary study outcome was the development of biliary atresia. Subgroup analysis was performed based on race, region, and assessment of Hardy-Weinberg equilibrium (HWE). RESULTS: The studies indicate that the ADD3 rs2501577 susceptibility locus increases the risk of developing biliary atresia, regardless of allelic, homozygote, dominant, and recessive gene inheritance models. Furthermore, ADD3 has been found to be associated with apoptosis, cell cycle, and cell damage repair based on functional analysis. CONCLUSIONS AND RELEVANCE: The ADD3 rs2501577 polymorphic locus is associated with an increased risk of biliary atresia, particularly in Asian populations. This study recommends further investigation of the ADD3 rs2501577 locus in Asian populations to validate its role in the diagnosis of biliary atresia.

The Impact of mNGS Technology in the Etiological Diagnosis of Severe Pneumonia in Children During the Epidemic of COVID-19.

Purpose: Metagenomic next-generation sequencing (mNGS) is an emerging technique for pathogen detection. However, most literature on the clinical application of pediatrics generally comprises case reports or small-scale cohort studies. Patients and Methods: A total of 101 children with community-acquired severe pneumonia admitted to Tianjin Children's Hospital from November 2021 to February 2022 were included. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected using mNGS. The performances of mNGS and conventional tests on pulmonary infection diagnosis and pathogen identification were compared. Results: According to our data, mNGS had a broader spectrum for pathogen detection. The mNGS results of BALF showed that the number of children with severe pneumonia hospitalized for mycoplasma pneumoniae infection was more than that for other bacterial infections during the COVID-19 epidemic. In addition, 43 cases (42.6%) had been identified with mixed infection, including 36 cases (35.6%) of Mycoplasma pneumoniae mixed with other pathogenic bacteria. Analytically, the mNGS exhibited significantly enhanced detection in the BALF as compared with the conventional laboratory pathogenic detection approaches (P < 0.05). The Pearson correlation analysis revealed positive correlation between the time of fever during hospitalization and the number of mycoplasma sequences (P < 0.05). Conclusion: Compared with traditional methods, mNGS has a higher etiological detection rate and can comprehensively detect various pathogens of severe pneumonia. Therefore, mNGS of bronchoalveolar lavage fluid should be performed in children with severe pneumonia, which is of great significance for guiding treatment.

Clinical Evaluation of Metagenomic Next-Generation Sequencing for the detection of pathogens in BALF in severe community acquired pneumonia.

BACKGROUND: Rapid and accurate identification of pathogens is very important for the treatment of Severe community-acquired pneumonia (SCAP) in children. Metagenomic Next-generation sequencing (mNGS) has been applied in the detection of pathogenic bacteria in recent years, while the overall evaluation the application of SCAP in children is lacking. METHODS: In our study, 84 cases of SCAP were enrolled. Bronchoalveolar lavage fluid (BALF) samples were analysed using mNGS; and sputum, blood, and BALF samples were analysed using conventional technology (CT). RESULTS: Among the 84 children, 41 were boys, and 43 were girls, with an average age ranging from 2 months to 14 years. The pathogen detection rate of mNGS was higher than that of CT (83.3% [70/84] vs. 63.1% [53/84], P = 0.003). The mNGS was much greater than that of the CT in detecting Streptococcus pneumoniae (89.2% [25/29] vs. 44.8% [13/29], P = 0.001) and Haemophilus influenzae (91.7% [11/12] vs. 33.3% [4/12], P < 0.005). The mNGS also showed superior fungal detection performance compared with that of the CT (81.8% [9/11] vs. 18.2% [2/11], P = 0.004). The mNGS test can detect viruses, such as bocavirus, rhinovirus, and human metapneumovirus, which are not frequently recognised using CT. However, the mNGS detection rate was lower than that of the CT (52.4% [11/21] vs. 95.2% [20/21], P = 0.004) for Mycoplasma pneumoniae (MP). The detection rate of mNGS for mixed infection was greater than that of the CT, although statistical significance was not observed (26.3% [20/39] vs. 21.1% [16/39], P > 0.005). Treatment for 26 (31.0%) children was changed based on mNGS results, and their symptoms were reduced; nine patients had their antibiotic modified, five had antibiotics added, nine had their antifungal medication, and seven had their antiviral medication. CONCLUSION: mNGS has unique advantages in the detection of SCAP pathogens in children, especially S. pneumoniae, H. influenzae, and fungi. However, the detection rate of MP using mNGS was lower than that of the CT. Additionally, mNGS can detect pathogens that are not generally covered by CT, which is extremely important for the modification of the treatment strategy.

A nomogram for the preoperative estimation of neuroblastoma risk despite inadequate biopsy information.

BACKGROUND AND PURPOSE: If the preoperative pathological information is inadequate, a risk classification may not be able to be determined for some patients with neuroblastoma. Our objectives were to include imaging factors, serum biomarkers, and demographic factors in a nomogram to distinguish high-risk patients before surgical resection based on the COG classification. METHOD: A total of 106 patients were included in the study. Of these, patients with clinicopathologically confirmed neuroblastoma at Tianjin Children's Hospital from January 2013 to November 2021 formed the training cohort (n = 82) for nomogram development, and those patients from January 2010 to December 2013 formed the validation cohort (n = 24) to confirm the model's performance. RESULT: On multivariate analysis of the primary cohort, independent factors for high risk were the presence of distant metastasis (p = 0.004), lactate dehydrogenase (LDH) (p = 0.009), and tumor volume (p = 0.033), which were all selected into the nomogram. The calibration curve for probability showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram was 0.95 95% [0.916-0.99]. Application of the nomogram in the validation cohort still gave good discrimination and good calibration. CONCLUSION: Three independent factors including the presence of distant metastasis, lactate dehydrogenase (LDH), and tumor volume are associated with high-risk neuroblastoma and selected into the nomogram. The novel nomogram has the flexibility to apply a clinically suitable cutoff to identify high-risk neuroblastoma patients despite inadequate preoperative pathological information. The nomogram can allow these patients to be offered suitable induction chemotherapy regimens and surgical plans. LEVELS OF EVIDENCE: Level III.

A novel model based on immune-related genes for differentiating biliary atresia from other cholestatic diseases.

PURPOSE: Based on a public gene expression database, this study established the immune-related genetic model that distinguished BA from other cholestasis diseases (DC) for the first time. We explored the molecular mechanism of BA based on the gene model. METHODS: The BA microarray dataset GSE46960, containing BA, other cause of intrahepatic cholestasis than biliary atresia and normal liver gene expression data, was downloaded from the Gene Expression Omnibus (GEO) database. We performed a comprehensive bioinformatics analysis to establish and validate an immune-related gene model and subsequently identified hub genes as biomarkers associated with the molecular mechanisms of BA. To assess the model's performance for separating BA from other cholestasis diseases, we used receiver operating characteristic (ROC) curves and the area under the curve (AUC) of the ROC. Independent datasets GSE69948 and GSE122340 were used for the validation process. RESULTS: The model was built using eight immune-related genes, including EDN1, HAMP, SAA1, SPP1, ANKRD1, MMP7, TACSTD2, and UCA1. In the GSE46960 and validation group, it presented excellent results, and the prediction accuracy of BA in comparison to other cholestasis diseases was good. Functional enrichment analysis revealed significant immunological differences between BA and other cholestatic diseases. Finally, we found that the TNFα-NF-κB pathway is associated with EDN1 gene expression and may explain fibrosis progression, which may become a new therapeutic target. CONCLUSION: In summary, we have successfully constructed an immune-related gene model that can distinguish BA from other cholestatic diseases, while identifying the hub gene. Our exploration of immune genes provides new clues for the early diagnosis, molecular mechanism, and clinical treatment of biliary atresia.

Efficacy of robot-assisted hepaticojejunostomy and laparoscopic-assisted hepaticojejunostomy in pediatric congenital choledochal dilatation: a system review and meta-analysis.

PURPOSE: The efficacy of robot-assisted hepaticojejunostomy (RAHJ) and laparoscopic-assisted hepaticojejunostomy (LAHJ) in children with congenital choledochal dilatation has been a topic of much debate and controversy. The purpose of this study was to evaluate the role of RAHJ and LAHJ in pediatric congenital choledochal dilatation. METHOD: The review program has been prospectively registered (PROSPEROID: CRD42022306868). We searched the PubMed, Embase, Cochrane, CBM, VIP, Web of Science, CNKI databases, and Wanfang databases from March 2021. The Mantel-Haenszel method and a random-effects model were used to figure out the hazard ratio (95% CI). RESULTS: Ten studies evaluated eight hundred and sixty-nine subjects (three hundred and thirty-two in the robotic group and five hundred and thirty-seven in the laparoscopic group), meeting all inclusion criteria. Compared with the laparoscopic group, robotic group demonstrated fewer postoperative complications [p = 0.0009; OR = 0.34 (95% CI, 0.18-0.64); I2 = 3%], shorter postoperative hospital stay [p < 00,001; MD = - 2.05 (95% CI, - 2.40-1.70); I2 = 0%], and less intraoperative bleeding [p = 0.008; MD = - 10.80 (95% CI, - 18.80-2.81); I2 = 99%]. There was no significant difference in operative time between the two groups [p = 0.10; MD = 24.53 (95% CI, - 5.11-54.17); I2 = 99%]. The same situation happened in short-term complication outcomes [p = 0.06; RR = 0.45 (95% CI, 0.19-1.04); I2 = 0%]. However, children in the RAHJ group had significantly lower levels of long-term complications [p = 0.04; OR = 0.41 (95% CI, 0.17-0.96); I2 = 0%]. Hospitalization costs were significantly higher in the RAHJ group [p < 0.00001; OR = 27,113.86 (95% CI, 26,307.24-27,920.48); I2 = 0%]. For overall complications, subgroup analysis of literature published after 2020 and of literature with high quality scores showed a significant decrease in the RAHJ group. CONCLUSION: In children with congenital choledochal dilatation, RAHJ is associated with reduced intraoperative bleeding, postoperative complications, and length of stay. Robotic surgery has a bright future in the treatment of pediatric common hepatic duct cysts and deserves to be promoted and popularized.

Primary exploring the value of metagenomic next-generation sequencing in detecting pathogenic bacteria of cholangitis with biliary atresia after Kasai operation.

PURPOSE: To evaluate the value of metagenomic next-generation sequencing (mNGS) in detecting pathogenic bacteria of cholangitis for patients with biliary atresia after Kasai operation. METHODS: This study retrospectively analyzed patients of biliary atresia with cholangitis after Kasai operation who were admitted to Xi'an Children's Hospital from July 2019 to December 2021. Both blood culture and mNGS were carried out in all of these patients. We compared the detection rate of pathogenic bacteria, pathogenic bacteria spectrum, test time, inflammatory indicators and liver function. All the patients were followed up for 0.5-3 years to evaluate the onset of cholangitis and the survival status of autologous liver. RESULTS: This study included total of 30 cholangitis occurred in 25 patients. There were significant differences in the detection rate of pathogenic bacteria [23.3 vs.73.3%, P < 0.05] and the test time [120 (114.5-120) vs.16 (16-21) h, P < 0.001] between the blood culture and mNGS. These two methods showed significant statistical differences in comparing inflammatory indicators (CRP, PCT) and liver function (TB, DB, GGT) before and after anti-infection. Four kinds of bacteria were detected by blood cultures and ten kinds of bacteria were detected by mNGS. Cholangitis occurred 3 times in one case (4%) and twice in three cases (12%). Autologous liver survived in 17 cases (68%). CONCLUSION: Comparing with traditional blood culture, mNGS is more efficient, convenient and accurate in the detection of pathogens. It provides a new method for accurately detecting pathogenic bacteria of cholangitis after Kasai operation.

Construction of a combined random forest and artificial neural network diagnosis model to screening potential biomarker for hepatoblastoma.

PURPOSE: The purpose of our study is to identify potential biomarkers of hepatoblastoma (HB) and further explore the pathogenesis of it. METHODS: Differentially expressed genes (DEGs) were incorporated into the combined random forest and artificial neural network diagnosis model to screen candidate genes for HB. Gene set enrichment analysis (GSEA) was used to analyze the ARHGEF2. Student's t test was performed to evaluate the difference of tumor-infiltrating immune cells (TIICs) between normal and HB samples. Spearson correlation analysis was used to calculate the correlation between ARHGEF2 and TIICs. RESULTS: ARHGEF2, TCF3, TMED3, STMN1 and RAVER2 were screened by the new model. The GSEA of ARHGEF2 included cell cycle pathway and antigen processing presenting pathway. There were significant differences in the composition of partial TIICs between HB and normal samples (p < 0.05). ARHGEF2 was significantly correlated with memory B cells (Cor = 0.509, p < 0.05). CONCLUSION: These 5 candidate genes contribute to the molecular diagnosis and targeted therapy of HB. And we found "ARHGEF2-RhoA-Cyclin D1/CDK4/CDK6-EF2" is a key mechanism regulating cell cycle pathway in HB. This will be helpful in the treatment of HB. The occurrence of HB is related to abnormal TIICs. We speculated that memory B cells play an important role in HB.

Clinical evaluation of metagenomic next-generation sequencing for detecting pathogens in bronchoalveolar lavage fluid collected from children with community-acquired pneumonia.

This study is to evaluate the usefulness of pathogen detection using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) specimens from children with community-acquired pneumonia (CAP). We retrospectively collected BALF specimens from 121 children with CAP at Tianjin Children's Hospital from February 2021 to December 2021. The diagnostic performances of mNGS and conventional tests (CT) (culture and targeted polymerase chain reaction tests) were compared, using composite diagnosis as the reference standard. The results of mNGS and CT were compared based on pathogenic and non-pathogenic organisms. Pathogen profiles and co-infections between the mild CAP and severe CAP groups were also analyzed. The overall positive coincidence rate was 86.78% (105/121) for mNGS and 66.94% (81/121) for CT. The proportion of patients diagnosed using mNGS plus CT increased to 99.18%. Among the patients, 17.36% were confirmed only by mNGS; Streptococcus pneumoniae accounted for 52.38% and 23.8% of the patients were co-infected. Moreover, Bordetella pertussis and Human bocavirus (HBoV) were detected only using mNGS. Mycoplasma pneumoniae, which was identified in 89 (73.55%) of 121 children with CAP, was the most frequent pathogen detected using mNGS. The infection rate of M. pneumoniae in the severe CAP group was significantly higher than that in the mild CAP group (P = 0.007). The symptoms of single bacterial infections (except for mycoplasma) were milder than those of mycoplasma infections. mNGS identified more bacterial infections when compared to the CT methods and was able to identify co-infections which were initially missed on CT. Additionally, it was able to identify pathogens that were beyond the scope of the CT methods. The mNGS method is a powerful supplement to clinical diagnostic tools in respiratory infections, as it can increase the precision of diagnosis and guide the use of antibiotics.

TGF-ß1-Mediated Leukocyte Cell-Derived Chemotaxin 2 Is Associated With Liver Fibrosis in Biliary Atresia.

Objective: Biliary atresia (BA) presents as a severe infantile cholangiopathy disease, characterized by progressive liver fibrosis and the resulting poor prognosis. Leukocyte cell-derived chemotaxin 2 (LECT2) was proposed as the key gene associated with hepatic fibrosis in BA, but the molecular mechanism is unclear. This study aims to investigate the function of LECT2 in BA. Methods: A total of 53 patients were enrolled in this study; 36 patients with BA, and 17 control patients with cholestasis, including congenital biliary dilations, biliary hypoplasia, and inspissated bile syndrome. The role of LECT2 in BA was analyzed using histological and cytological tests. The correlation between LECT2 and infiltrating immune cells was further analyzed by bioinformatics. The analyses were conducted using correlational analyses and ROC curves. Results: LECT2 was highly expressed in infants with BA and positively related with fibrosis (0.1644 ± 0.0608 vs. 0.0779 ± 0.0053, p < 0.0001; r s = 0.85, p < 0.0001). Serum levels of LECT2 showed high distinguishing features for patients with BA having an AUC of 0.95 (95% CI: 0.90-1.00). CD163 was highly expressed in the aggravation of fibrosis (0.158 ± 0.062 vs. 0.29 ± 0.078, p < 0.0001), and the expression of LECT2 was positively correlated with the accumulation of CD163+ macrophages (r = 0.48, p = 0.003). The bioinformatic analysis also showed that LECT2 was positively correlated with macrophage M2 (r = 0.34, p = 0.03). TGF-ß1 and CD163 colocalized to the portal area in the livers of patients with BA. Moreover, TGF-ß1 upregulated the expression of LECT2. Conclusion: LECT2 is highly expressed in both BA liver tissue and serum, and serum LECT2 is a potential diagnostic biomarker of BA. Meanwhile, TGF-ß1 is secreted by macrophages to regulate LECT2 associated with BA liver fibrosis.

Fabrication and Investigation of PE-SiO2@PZS Composite Separator for Lithium-Ion Batteries.

Commercial polyolefin separators exhibit problems including shrinkage under high temperatures and poor electrolyte wettability and uptake, resulting in low ionic conductivity and safety problems. In this work, core-shell silica-polyphosphazene nanoparticles (SiO2@PZS) with different PZS layer thicknesses were synthesized and coated onto both sides of polyethylene (PE) microporous membranes to prepare composite membranes. Compared to pure silica-coated membranes and PE membranes, the PE-SiO2@PZS composite membrane had higher ionic conductivity. With the increase in the SiO2@PZS shell thickness, the electrolyte uptake, ionic conductivity and discharge capacity gradually increased. The discharge capacity of the PE-SiO2@PZS composite membrane at 8 C rate was 129 mAh/g, which was higher than the values of 107 mAh/g for the PE-SiO2 composite membrane and 104 mAh/g for the PE membrane.

Therapeutic Endoscopic Retrograde Cholangiopancreatography for Pediatric Hepato-Pancreato-Biliary Diseases: A Systematic Review and Meta-Analysis.

Background: Hepato-pancreato-biliary (HPB) disease has different causes and types between children and adults, which has been increasingly diagnosed in the pediatric group. Endoscopic retrograde cholangiopancreatography (ERCP) has been gradually considered as a therapeutic method in adults, while in pediatric patients, there are not many reports of its usage. This systematic review and meta-analysis aims to assess the use condition of therapeutic ERCP in the management of pediatric HPB diseases. Methods: This systematic literature search was conducted in the PubMed, Embase, Web of Science, and Cochrane library databases to identify all relevant articles published from inception to February 2022 that evaluated therapeutic ERCP in pediatric patients with HPB diseases. The researchers included studies in which patients were less than 18 years old and underwent therapeutic ERCP procedures. A random-effects model was used to analyze the usage rate of therapeutic ERCP procedures, procedural success rates, adverse event rates, and the rate of different therapeutic procedures. Subgroup analysis, sensitivity analysis, and meta-regression were conducted to analyze the source of heterogeneity. Results: A total of 33 articles were included. After homogenization, the overall use of therapeutic interventions accounts for 77% [95% confidence interval (CI) 74-81%] of all ERCP procedures. After excluding outlier studies, the estimation success rate of the therapeutic procedure is 74% (95% CI 69-79%), and adverse event rate is 8% (95% CI 6-10%). In our study, stent placement is the most common procedure, which makes up 75% (95% CI 65-86%) of all therapeutic procedures. In addition, the usage proportion of sphincterotomy (ST), stone extraction/removal, bougienage/balloon dilation is, respectively, 46% (95% CI 39-53%), 34% (95% CI 31-38%), and 26% (95% CI 22-29%). Conclusion: The ERCP procedure is gradually considered a therapeutic technique in pediatric patients, the proportion of therapeutic ERCP is 77% of total usage, which is increasing every year. Meanwhile, its success rate is relatively high. It reflects that this operation modality is promising in the treatment of HPB disorders and is gradually expanded as more branch technologies are being used. A variety of operations can be achieved through ERCP procedures, and more functions should be developed in the future. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022302911].