Proteasome-associated autoinflammatory syndrome 2 in a neonate.

Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is characterized by early onset combined immunodeficiency, inflammatory neutrophilic dermatosis, and autoimmunity. We report the case of a premature baby (GA 35+5 weeks) born with disseminated and confluent red papules, diagnosed with PRAAS2. A novel de novo frameshift proteasome maturation protein (POMP) mutation (c.333delT (p.t111fs)) was detected, confirming the diagnosis.

RP11-40C6.2 Inactivates Hippo Signaling by Attenuating YAP1 Ubiquitylation in Hepatitis B Virus-associated Hepatocellular Carcinoma.

Background and Aims: Chronic hepatitis caused by hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). We investigated the roles of oncogenic HBV infection-associated long noncoding RNAs in HCC. Methods: Bioinformatics analysis of data from the Cancer Genome Atlas (TCGA) was performed to screen potential oncogenic HBV-related lncRNAs. Next, we assessed their expression in clinical samples and investigated their correlation with clinical characteristics. The detailed oncogenic effects were analyzed by performing in vitro and in vivo studies. Results: RP11-40C6.2, an HBV infection-related lncRNA, was identified by analysis of the TCGA-Liver Hepatocellular Carcinoma database. Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes revealed a strong association of RP11-40C6.2 with the Hippo signaling pathway. RP11-40C6.2 was overexpressed in HCC patients with HBV infection compared to those without HBV infection. RP11-40C6.2 transcription showed a positive association with HBV-X protein (HBx), but not HBV core protein (HBc) expression, both of which are carcinogenic proteins. Luciferase gene reporter and ChIP assays revealed that YAP1/TAZ/TEADs complex enhanced RP11-40C6.2 transcription by binding to its promoter area. RP11-40C6.2 showed oncogenic characteristics in HCC cell lines and in animal models that were mediated via activation of YAP1. In vitro ubiquitylation assay revealed that RP11-40C6.2 can promote the stabilization of YAP1 by stopping phosphorylation at its s127 residue and further stopping its degradation through binding to 14-3-3. Conclusions: RP11-40C6.2 is an HBV infection-related lncRNA that exerts its oncogenic effects by targeting the Hippo signaling pathway.

CircMYH9 increases KPNA2 mRNA stability to promote hepatocellular carcinoma progression in an EIF4A3-dependent manner.

Hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer worldwide with a high incidence of recurrence and metastasis; however, the molecular mechanisms underlying HCC development remain to be fully understood. In this study, we identified circMYH9 as an important regulator of HCC. Overexpression of circMYH9 induced, while knockdown of circMYH9 inhibited, the proliferation, migration, and invasion of HCC cells. Mechanistically, circMYH9 bound to eukaryotic translation initiation factor 4A3 (EIF4A3) and increased karyopherin subunit alpha 2 (KPNA2) mRNA stability. circMYH9 knockdown in HCC cells reduced the stability of KPNA2 mRNA. Importantly, circMYH9 regulation of HCC required the activity of KPNA2. In support with this, circMYH9 level was positively correlated with the expression of KPNA2 in HCC patient samples. Taken together, our study was the first to uncover the oncogenic role of circMYH9 in HCC and further elucidated the functional mechanism of circMYH9 by interacting with EIF4A3 to increase KPNA2 mRNA stability. Our findings might provide a novel potential target for the diagnose and treatment of HCC.

A comprehensive framework of the right posterior section for tailored anatomical liver resection based on three-dimensional simulation system.

Background: The anatomical right posterior sectionectomy (ARPS) is a technically challenging procedure. We aimed to develop and validate a novel framework of the right posterior section for a safe and tailored anatomical liver resection (ALR) based on a three-dimensional (3D) simulation system. Methods: 3D hepatectomy simulations of healthy participants who underwent contrast-enhanced computed tomography of the upper abdomen were retrospectively reviewed to develop the framework according to the relationship between the simulated plane determined by the right posterior portal pedicle (RPP) and the course of the right hepatic vein (RHV) trunk. The framework was validated in the practice of ARPS for hepatocellular carcinoma (HCC) prospectively. Results: Scans from 336 eligible participants were assessed. The framework was summarized into four types: normal, caudal-redundant, cranial-deficient, and combined types, accounting for 43.4% (146/336), 25.3% (85/336), 18.5% (62/336), and 12.8% (43/336) respectively. The caudal-redundant type was associated with the variable portal branches of the RPP or segment 6 branch across the ventral side of RHV. The mean aberrant volume proportion in type IIa was significantly greater than that in type IIb (P<0.001), which were 7.0%±3.5% and 4.4%±1.8% respectively. The cranial-deficient type was associated with the aberrant segment 7 portal pedicle originating from the right portal trunk or the dorsal portal branch of segment 8 crossing over to the RHV. The median aberrant volume proportion in type IIIa was significantly greater than that in type IIIb (P<0.001), which were 10.9% (8.5-13.3%) and 4.0% (3.0-6.1%), respectively. The combined type represented a combination of the caudal-redundant type and the cranial-deficient type. The framework provided instructions on tailored ARPS in 6 patients with HCC by maximizing lesion removal and functional liver remnant with favorable perioperative outcomes. Conclusions: Precise preoperative planning with an individualized surgical approach based on our framework allows safe anatomical liver resections for cases with lesions in the right posterior section.

CircASPH Promotes Hepatocellular Carcinoma Progression Through Methylation and Expression of HAO2.

CircRNAs have been reported to be related to hepatocellular carcinoma (HCC) development. Limited studies have revealed the expression profile of circRNAs in tumor and para-tumor normal samples in HCC patients. We found that circASPH was significantly increased in HCC tumor samples and that the level of circASPH was closely related to the overall survival of HCC patients. Mechanistically, circASPH could regulate the methylation of the promoter and expression of hydrocyanic oxidase 2 (HAO2) to promote HCC progression by acting as a sponge for miR-370-3p, and miR-370-3p could target DNMT3b and increase the 5mC level. In summary, our study determined that circASPH could regulate the methylation and expression of HAO2 and it could be considered an important epigenetic regulator in HCC progression.

Surgical Strategy for Resecting Hepatocellular Carcinoma in the Caudate Lobe: Isolated or Combined Lobectomy? A Single-Center Study and Meta-Analysis.

BACKGROUND: Resection of hepatocellular carcinoma (HCC) originating in the caudate lobe remains challenging, while the optimal extent of resection is debated. We aimed to evaluate the relative benefits of combined caudate lobectomy (CCL) versus isolated caudate lobectomy (ICL) for caudate HCC. METHODS: Patients who underwent curative-intent resection for caudate HCC between January 2010 and December 2018 were identified from a single-center database. Surgical outcomes of the two strategy groups were analyzed before and after propensity score matching. A systematic review with meta-analysis was also performed to compare outcomes of CCL versus ICL for caudate HCC. RESULTS: A total of 28 patients were included: 11 in the CCL and 17 in the ICL group. Compared with ICL, the CCL group contained patients with larger tumors and a higher incidence of vascular invasion. After propensity score matching, 6 pairs of patients were selected. In the well-matched cohort, CCL demonstrated significantly improved recurrence-free survival (RFS) (P = 0.047) compared with ICL; no significant differences were noted for overall survival (OS), operation time, blood loss and morbidity rate. A total of 227 patients from nine eligible studies and ours were involved in the systematic review. Meta-analysis revealed that CCL provided better RFS (hazard ratio 0.54, 95% confidence interval 0.31-0.92) than ICL; no significant differences were observed in OS, operation time, blood loss and morbidity rate. CONCLUSION: CCL confers superior RFS over ICL without compromise of perioperative outcomes and should be prioritized for patients with caudate HCC when feasible, especially for those with large-sized tumors.

Case Report: Congenital diaphragmatic hernia associated with esophageal atresia and tracheoesophageal fistula.

The coexistence of congenital diaphragmatic hernia and esophageal atresia with or without tracheoesophageal fistula is extremely rare; only 36 cases have been reported. We report a case of a preterm male newborn infant with left congenital diaphragmatic hernia, esophageal atresia, and tracheoesophageal fistula and review 27 related cases.

Effect of Mo Concentration on the Microstructure Evolution and Properties of High Boron Cast Steel.

The microstructure evolution, mechanical properties, and tribological properties of high boron cast steel (HBCS) with various Mo concentrations are investigated. The results indicate that Mo addition can significantly modify the microstructure and enhance the comprehensive properties. With the increase of Mo concentration, borides change from the original fish-bone Fe-rich and Cr-rich M2B to dendritic Fe-rich M2B, blocky and cluster-like Cr-rich M2B, and grainy Mo-rich M2B. The hardness of HBCS increases gradually with the increase of Mo content due to the solid solution strengthening and the refinement of M2B. It can be found that all the samples exhibit quasi-cleavage, but the impact toughness increases firstly and reaches the maximum value when the concentration of Mo is 2.10 wt.%, which is the result of the dispersive distribution of M2B rather than the original fish-bone M2B. Subsequently, the impact toughness begins to decrease as the concentration of Mo further increases because of the extensive formation of grainy Mo-rich M2B at the grain boundary. Meanwhile, the wear results reveal that the average friction coefficient and wear ratio decrease with the increase of Mo content, and the wear mechanism changes from abrasive wear and adhesive wear to abrasive wear when the concentration of Mo exceeds 2.10 wt.%.