Prediction of early recovery of graft function after living donor liver transplantation in children.

For end-stage liver disease in children, living donor liver transplantation (LDLT) is often the important standard curative treatment. However, there is a lack of research on early recovery of graft function after pediatric LDLT. This is a single-center, ambispective cohort study. We collected the demographic and clinicopathological data of donors and recipients, and determined the risk factors of postoperative delayed recovery of hepatic function (DRHF) by univariate and multivariate Logistic analyses. 181 cases were included in the retrospective cohort and 50 cases in the prospective cohort. The incidence of DRHF after LDLT in children was 29.4%, and DRHF could well evaluate the early recovery of graft function after LDLT. Through Logistic analyses and AIC score, preoperative liver function of donors, ischemia duration level of the liver graft, Ln (Cr of recipients before operation) and Ln (TB of recipients on the 3rd day after operation) were predictive indicators for DRHF after LDLT in children. Using the above factors, we constructed a predictive model to evaluate the incidence of postoperative DRHF. Self-verification and prospective internal verification showed that this prediction model had good accuracy and clinical applicability. In conclusion, we pointed many risk factors for early delayed recovery of graft function after LDLT in children, and developed a visual and personalized predictive model for them, offering valuable insights for clinical management.

Role of m6A modification in regulating the PI3K/AKT signaling pathway in cancer.

The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays a crucial role in the pathogenesis of cancer. The dysregulation of this pathway has been linked to the development and initiation of various types of cancer. Recently, epigenetic modifications, particularly N6-methyladenosine (m6A), have been recognized as essential contributors to mRNA-related biological processes and translation. The abnormal expression of m6A modification enzymes has been associated with oncogenesis, tumor progression, and drug resistance. Here, we review the role of m6A modification in regulating the PI3K/AKT pathway in cancer and its implications in the development of novel strategies for cancer treatment.

High expression of RPL27A predicts poor prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the digestive system with rapid progression and poor prognosis. Recent studies have shown that RPL27A could be used as a biomarker for a variety of cancers, but its role in HCC is not clear. METHOD: We analyzed the expression of RPL27A in the pan-cancer analysis and analyzed the relationship between the expression of RPL27A and the clinical features and prognosis of patients with HCC. We evaluated the expression difference of RPL27A in HCC tissues and paired normal adjacent tissues using immunohistochemistry. Furthermore, we analyzed the co-expression genes of RPL27A and used them to explore the possible mechanism of RPL27A and screen hub genes effecting HCC. In addition, we studied the role of RPL27A in immune infiltration and mutation. RESULTS: We found that the expression level of RPL27A increased in a variety of cancers, including HCC. In HCC patients, the high expression of RPL27A was related to progression and poor prognosis as an independent predictor. We also constructed a protein interaction network through co-expression gene analysis of RPL27A and screened 9 hub genes. Enrichment analysis showed that co-expression genes were associated with ribosome pathway, viral replication, nuclear-transcribed mRNA catabolic process, and nonsense-mediated decay. We found that the expression level of RPL27A was closely related to TP53 mutation and immune infiltration in HCC. CONCLUSION: RPL27A might become a biomarker in the diagnosis, treatment, and follow-up of patients with HCC.

Transplacental transmission of SARS-CoV-2 immunoglobulin G antibody to infants from maternal COVID-19 vaccine immunization before pregnancy.

The coronavirus disease 2019 (COVID-19) vaccine generates functional antibodies in maternal circulation that are detectable in infants, while the information is restricted to the usage of COVID-19 vaccine during pregnancy. In this study, we aimed to evaluate the effect of maternal COVID-19 vaccines before pregnancy. Infants were included from mothers with no inactivated COVID-19 vaccine, 1-, 2-, and 3-dose before pregnancy, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibodies were tested. Comparative analysis was done between the groups. A total of 130 infants were enrolled in the study. Significantly higher levels of SARS-CoV-2 IgG antibodies in infants born to mothers with 3-dose COVID-19 vaccine before pregnancy compared with 1- and 2-dose groups (p < 0.0001). The levels of antibodies decreased significantly with age in infants born to mothers with the 3-dose COVID-19 vaccine before pregnancy (r = -0.338, p = 0.035), and it was still higher than that 2-dose COVID-19 vaccine group. The maternal SARS-CoV-2 antibodies produced from the inactivated COVID-19 vaccine before pregnancy can be transferred to newborns via the placenta. Maternal immunization with 3-dose of the COVID-19 vaccine before pregnancy could be more beneficial for both mothers and infants.

Incidence trends and predictive model of hepatic malignant tumors in children: a population-based study.

OBJECTIVE: To analyze the incidence trend and establish a model to predict the prognosis of hepatic malignant tumors in children (CHMTs). METHODS: We analyzed the incidence data of CHMTs from 1975 to 2018 from the Surveillance, Epidemiology, and End Results (SEER) database, and evaluated the incidence trends based on different demographic and pathological features. We also analyzed clinicopathologic data from 2000 to 2018 from the SEER database. Univariate and multivariate Cox regression analyses were performed to explore prognostic factors related to overall survival (OS). Then, we established nomograms based on independent predictors and verified them using receiver operating characteristic curves, calibration plots, and decision curve analysis plots. RESULTS: The incidence of CHMTs increased significantly, from 0.1 per 100,000 in 1975 to 0.4 per 100,000 in 2018. Incidences among different races and genders were increasing and converging. The incidence of hepatoblastoma (HB) increased, while that of hepatocellular carcinoma (HCC) was relatively stable. The 1-, 3-, 5-, and 10-year OS rates were 86.2%, 77.5%, 74.2%, and 70.2%, respectively. Being Spanish-Hispanic-Latino, HB, surgery, and systemic therapy were independent predictors of longer OS, whereas regional and distant stages were independent predictors of shorter OS. Nomograms with good predictive ability and clinical utility were established to evaluate the prognosis of children with HB or HCC. CONCLUSION: The incidence of CHMTs is increasing, especially for HB and in younger children. This study identified independent predictors and developed nomograms that could provide a personalized and accurate prognosis for CHMTs.

Lead exposure as a causative factor for metabolic associated fatty liver disease (MAFLD) and a lead exposure related nomogram for MAFLD prevalence.

The relationship between lead exposure and neurological disorders has been extensively studied, but the effects of lead exposure on hepatotoxicity are unknown. Metabolically related fatty liver disease (MAFLD) is an update of previous non-alcoholic fatty liver disease (NAFLD). It redefines the diagnostic conditions and emphasizes metabolic factors while considering non-alcoholic factors. Lead can affect the endocrine system and metabolism, so we believe that lead exposure may contribute to MAFLD. 41,723 individuals who had undergone blood lead testing from 2005 to 2018 in the National Health and Nutrition Examination Survey (NHANES) database were selected for this study. The characteristics of population lead exposure in the last decade or so, the effect of lead exposure on liver function and whether lead exposure can cause MAFLD were analyzed. Co-variates were adjusted according to age, ethnicity, body mass index (BMI), waist circumference, visceral adiposity index (VAI), poverty indices (PIR), diabetes, hypertension, and hyperlipidemia. The results showed that blood lead concentrations stabilized at a low level after a decreasing trend from year to year. The differences in blood lead concentrations were associated with differences in age, sex, race, education level, and PIR. Lead exposure was an independent risk factor for MAFLD, and lead and nine other factors were used as independent risk factors for MAFLD, so a nomogram was established to predict the prevalence probability of MAFLD.

Competitive risk analysis of the therapeutic value of liver transplantation for liver cancer in children: A population-based study.

Background: Liver transplantation (LT) is one of the most important treatments for children with liver cancer (CLCa) and has been increasingly used. However, there is a lack of large-scale and multicenter studies on the trend in the application and value of LT for the treatment of CLCa. Methods: We analyzed the clinicopathological data of CLCa from 2000 to 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. We explored the trend in the application of LT for the treatment of CLCa. LASSO Cox regression and the Log-Rank test were used to explore prognostic factors, and we built a nomogram using the screened factors. Propensity score matching was used to balance the baseline data of patients undergoing LT and other surgeries, and then the Log-Rank test was used to evaluate the therapeutic value of LT for CLCa. Results: The 1-year, 3-year, 5-year, and 10-year overall survival (OS) rates of CLCa were 88.7%, 80.6%, 76.8%, and 73.0%, respectively. Then, we established a nomogram using many variables including age of diagnosis, regional lymph node metastasis, summary stage, and therapy. Internally validated and externally verified, our nomogram had good predictive power and clinical applicability. LT was increasingly being used to treat CLCa. There was no statistically significant difference in the OS of CLCa between the LT and other surgeries groups. After LT, the hepatoblastoma group had a better prognosis than the hepatocellular carcinoma group. Conclusion: We built a well-performing nomogram to predict the OS of CLCa. LT could improve the prognosis of CLCa as other surgeries and could be considered an effective treatment choice for CLCa.

A sewing needle in the liver in children: A case report and literature review.

RATIONALE: In clinical practice, foreign bodies (FBs) in the digestive tract are more common in children, but intrahepatic FBs are rare, especially those that can cause infection, bleeding, bile leakage, and other complications. However, there is no consensus on its diagnosis and treatment due to the lack of large-scale cohort studies. PATIENT CONCERNS: Case 1 is a 4-years 8-months-old girl, who at the age of 10 months, showed an X-ray finding of a striped FB in her liver, with no symptoms. However, the patient's parents refused surgery. After nearly 4 years of active surveillance, the patient visited our hospital for surgery. Case 2, a 2-year-old male, reported a sewing needle that completely pierced into the right upper abdomen due to an accidental fall that took place half-a-day before admission. He only had right upper abdominal pain. CT showed a striped FB in the liver. DIAGNOSIS: FB in the liver (sewing needle). INTERVENTIONS: Both the patients were injected with human tetanus immunoglobulin and underwent surgical removal. OUTCOMES: Both patients recovered smoothly and had no complications during follow-up. LESSONS: Active surveillance might be considered for cases with no symptoms or complications and no displacement of the FB, but surgery should be the first choice. If the patient's condition is complicated, it is recommended to use ultrasound or X-ray to help decision-making during the operation. Additionally, tetanus, child safety, and family education are important supportive measures.

Learning Curve Analysis of Microvascular Hepatic Artery Anastomosis for Pediatric Living Donor Liver Transplantation: Initial Experience at A Single Institution.

Background: The incidence of hepatic artery thrombosis in pediatric living donor liver transplantation (LDLT) is significantly higher than that in adults, and is closely related to the surgeon's experience with hepatic artery anastomosis. However, there are few studies on the learning curve of hepatic artery anastomosis among surgeons. Methods: We collected data related to 75 patients who underwent pediatric LDLT and hepatic artery anastomosis independently by the same surgeon. Cumulative sum method (CUSUM) was used to analyse the duration of hepatic artery anastomosis and determine the cut-off value. Patients were divided into two phases according to CUSUM. We analysed the intraoperative and postoperative data and survival outcomes of the included patients. Results: Total anastomosis duration decreased with an increased number of completed procedures, and the average duration was 42.4 ± 2.20 min. A cut-off value and two phases were identified: 1-43 cases and 44-75 cases. Intraoperative blood loss was significantly lower in phase 2 than in phase 1. The immediate functional changes of total bilirubin (TBIL) and direct bilirubin (DBIL) were significantly also lower in phase 2 than in phase 1. Other functional outcomes, postoperative complications, and the long-term survival rate were not significantly different between the two phases. Conclusions: Technical competence in pediatric LDLT hepatic artery anastomosis may be achieved after completing 43 cases. It is a safe procedure with a surgical loupe that can be systematized and adopted by pediatric surgeons with sufficient experience via a relatively long learning curve.

Immune Characteristics in Biliary Atresia Based on Immune Genes and Immune Cell Infiltration.

Background: Biliary atresia (BA) is a serious biliary disease in infancy. Jaundice is the most visual and prominent symptom, and it mainly involves bile duct cells leading to the loss of intrahepatic and extrahepatic bile ducts. If left untreated, it will eventually progress to liver cirrhosis. The pathogenesis of BA is not clear, and it is now generally accepted that BA is an autoimmune disease. However, few studies have revealed the infiltration of immune cells in the liver of BA from a global perspective. We used liver tissue sequencing data to predict the infiltration and relative content of immune cells in BA. Methods: The BA datasets GSE46960, GSE15235, and GSE84044, and patient information were downloaded from the Gene Expression Omnibus (GEO) database. After batch normalization, the differentially expressed immune genes (DE-IGs) in BA liver, normal liver, and hepatitis B liver were analyzed with the cut-off value of |log2fold change (log2FC)| >1 and false discovery rate (FDR) <0.05. CIBERSORT software was used to predict the proportions of 22 immune cells in all samples of the datasets. Results: 73 DE-IGs have been screened out between BA and normal tissue; among them, 20 genes were highly expressed and another 53 were expressed at a low level. A total of 30 DE-IGs existed between inflammation and fibrosis livers of BA, and all of them were expressed at low levels in fibrosis livers of BA. In GO term analysis, these DE-IGs were mainly associated with the MHC protein complex, cytokine, chemokine activity, and MHC-II receptor activity. In KEGG pathway analysis, the DE-IGs were mainly enriched in pathways of Th1 and Th2 cell differentiation, Th17 cell differentiation, IL-17 signaling pathway, Toll-like receptor signaling pathway, TNF signaling pathway, and autoimmune diseases. There were significant differences in immune infiltration among different pathological types of BA, and there were also obvious differences in immune infiltration of hepatitis B as a disease control of BA. Conclusion: Based on immune genes and immune cell infiltration, this study reveals the immune characteristics of BA from a global point of view, which provides a new perspective for understanding the pathogenesis of BA and provides a direction for the diagnosis and treatment of BA.

Incidence Trend and Competing Risk Analysis of Patients With Intrahepatic Cholangiocarcinoma: A Population-Based Study.

Background: Intrahepatic cholangiocarcinoma (ICCA) is a primary liver cancer characterized by rapid progression and poor prognosis. There are few effective tools for evaluating the prognosis of ICCA patients, and the use of liver transplantation (LT) of the treatment for ICCA is still controversial. Methods: We analyzed ICCA incidence data and clinicopathological data from the Surveillance, Epidemiology, and End Results database. Prognostic predictors were identified by univariate and multivariate Cox regression analyses and then used to establish a nomogram. The prediction performance of the nomogram was evaluated with receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis (DCA) plots. Propensity score matching (PSM) was used to balance the baseline data of patients undergoing LT and other operations, and then, univariate Cox regression analysis was used to evaluate the therapeutic value of LT for ICCA. Results: The incidence of ICCA increased significantly, from 0.6 per 100,000 in 2,000 to 1.3 per 100,000 in 2018. The median overall survival (OS) of the patients was 13 months, and the 1-, 3-, and 5-year OS rates were 51.40, 22.14, and 13.79%, respectively. Cox regression analysis showed that age under 60 years old, female, tumor size ≤ 50 mm, better differentiation, smaller range of tumor invasion, lack of distant metastasis, regional lymph node surgery and treatment were associated with a better prognosis. The ROC curves, calibration plots, and DCA plots showed that the nomogram had good discrimination and calibration power, as well as clinical utility. After PSM, the univariate Cox regression analysis showed no significant difference in OS between patients treated with LT and patients treated with other operations. Conclusion: The incidence of ICCA increased significantly. A nomogram with good predictive performance was developed to predict the OS of ICCA patients. LT might be considered as a potential option for some ICCA patients.

Long Noncoding RNA MNX1 antisense RNA 1 Exerts Oncogenic Functions in Bladder Cancer by Regulating miR-218-5p/RAB1A Axis.

LncRNA MNX1 antisense RNA 1 (MNX1-AS1) is significantly overexpressed in patients with bladder cancer, suggesting that it might be associated with bladder cancer. However, the molecular mechanism of MNX1-AS1 in bladder cancer remained indistinct. To illustrate the role of MNX1-AS1 in bladder cancer, the gain- and loss-of-function experiments were conducted in bladder cancer cells. Reduced expression of MNX1-AS1 could suppress cell proliferation, migration, invasion, and epithelial-mesenchymal transition in bladder cancer cells, whereas overexpression of MNX1-AS1 resulted in the opposite effects. Mechanistic analysis demonstrated that miR-218-5p was a direct target of RAB1A. MNX1-AS1 could competitively bind to miR-218-5p to regulate RAB1A expression in bladder cancer cells. Furthermore, in vivo experiments revealed that reduced expression of MNX1-AS1 inhibited tumor growth and metastasis. Taken together, MNX1-AS1 functions as a sponge to miR-218-5p to modulate RAB1A expression in bladder cancer, which suggests that MNX1-AS1 might serve as a novel therapeutic target and a novel biomarker for metastasis and prognosis in bladder cancer. SIGNIFICANCE STATEMENT: Our study demonstrates that long noncoding RNA MNX1-AS1 promotes the initiation and progression of bladder cancer. MNX1-AS1 regulates RAB1A expression to promote proliferation, migration, invasion, and epithelial-mesenchymal transitions of bladder cancer cells via miR-218-5p, which contributes to the tumor growth and metastasis of bladder cancer. Collectively, these results suggest that MNX1-AS1 might serve as a potential biomarker for bladder cancer.