Purpose: Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear. Materials and Methods: Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry. Results: CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway. Conclusion CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.

Objective:To investigate the clinical application of continuous renal replacement therapy (CRRT) in infants with acute kidney injury (AKI) after liver transplantation.Methods:A retrospective study was conducted on infants with AKI after liver transplantation in Tianjin First Center Hospital from January 1, 2019 to June 1, 2021. Infants with AKI within 1 year after liver transplantation were divided into CRRT group and non-CRRT group according to whether CRRT was performed. The preoperative and intraoperative condition, the postoperative complications were compared, the risk factors of CRRT for AKI infants, the clinical characteristics of CRRT were analyzed, and the prognosis between CRRT group and non-CRRT group were compared.Results:① A total of 512 cases of pediatric liver transplantation were performed. A total of 189 cases (36.9%) developed AKI within 1 year after surgery, including 18 cases in CRRT group and 171 cases in non-CRRT group. ② There was no significant difference in preoperative conditions between the two groups. The duration of liver transplantation (hours: 8.8±1.5 vs. 7.5±1.3) and intraoperative blood loss [mL: 370 (220-800) vs. 310 (200-400)] in CRRT group were significantly higher than those in non-CRRT group. CRRT group had significantly higher incidence of postoperative complication [unplanned operation: 8 cases (44.4%) vs. 14 cases (8.2%), primary nonfunction: 1 case (5.6%) vs. 0 case (0%), retransplantation: 3 cases (16.7%) vs. 0 case (0%), hepatic artery thrombosis: 3 cases (16.7%) vs. 4 cases (2.3%), intestinal fistula: 2 cases (11.1%) vs. 2 cases (1.2%)] than non-CRRT group (all P < 0.05). ③ The average start time of CRRT was 10 (1-240) days. The per capita frequency of CRRT treatment was 3.3 (1.0-14.0) times. The average duration of each CRRT treatment was 10.1 (6.0-19.3) hours, the average reduction rate of serum creatinine (SCr) was 25.6% (13.5%-45.0%) after CRRT. ④ In CRRT group, 5 patients died, the 1-year and 2-year survival rates were both 72.22%. In non-CRRT group, 6 patients died, the 1-year and 2-year survival rates were 97.1% and 96.5%, respectively. There were significant differences in 1-year and 2-year survival rates between the two groups (both P < 0.01). Conclusions:The incidence of AKI after pediatric liver transplantation was high, and most infants treated with CRRT were associated with serious surgical complications. CRRT was a powerful means to remove inflammatory factors and maintain the stability of circulation and internal environment, which could improve the multi-organ dysfunction effectively.

Background Parabens, a widely used class of preservatives, are suspected to be potential obesogens as emerging endocrine disrupting chemicals with reproductive and developmental toxicity. Objective To analyze five urinary parabens (PBs) and estimate the associations of exposure to PBs with adiposity measures in 10-year-old school-age children. Methods A total of 471 school-age children aged 10 years from the Sheyang Mini Birth Cohort were enrolled in this study. A questionnaire survey was conducted to collect socio-demographic information, physical activity, and dietary intake. Weight, height, and waist circumference of children were measured, and age- and sex-adjusted body mass index (BMI-Z score) was calculated. Spot urine samples were collected during the follow-up visits. Urinary concentrations of five PBs including methyl-paraben (MeP), ethyl-paraben (EtP), propyl-paraben (PrP), butyl-paraben (BuP), and benzyl-paraben (BzP) were detected by gas chromatography-tandem mass spectrometry (GC-MS/MS). Generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR) models were applied to estimate associations of individual/overall urinary PBs concentrations with BMI Z-score and waist circumference. Results The positive rates of selected five urinary PBs were in the range from 78.98% to 98.94%. The urinary PBs concentrations (geometric mean) were in the range of 0.31-5.43 μg·L⁻¹. The children's BMI Z-score and waist circumference (mean ± standard deviation) were (0.56±1.40) and (67.62±10.07) cm respectively. The GLMs results showed that the urinary BzP concentration was negatively associated with waist circumference (b=−0.08, 95%CI: −0.14, −0.02; P=0.01). In sex-stratified analysis, the urinary concentration of BzP was negatively associated with BMI-Z score (b=−0.59, 95%CI: −0.88, −0.30; P<0.001) and waist circumference (b=−0.80, 95%CI: −1.23, −0.37; P<0.001) in boys, but not in girls. The BKMR results also found significant negative correlations of urinary BzP concentrations with BMI-Z score and waist circumference, which were consistent with the GLM results. Conclusion The selected 10-year-old children are extensively exposed to PBs in the study area. Furthermore, childhood PBs exposure may have potential impacts on childhood adiposity measures with sex-specific effects.