Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal maintenance is poorly understood. Here, we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs. Human HAND2-AS1 and its mouse ortholog lncHand2 display a high level of conservation. HAND2-AS1 is required for the selfrenewal maintenance of liver CSCs to initiate HCC development. Mechanistically, HAND2-AS1 recruits the INO80 chromatin-remodeling complex to the promoter of BMPR1A, thereby inducing its expression and leading to the activation of BMP signaling. Importantly, interfering with expression of HAND2-AS1 by antisense oligonucleotides (ASOs) and BMPR1A by siRNAs has synergistic antitumorigenic effects on humanized HCC models. Moreover, knockout of lncHand2 or Bmpr1a in mouse hepatocytes impairs BMP signaling and suppresses the initiation of liver cancer. Our findings reveal that HAND2-AS1 promotes the self-renewal of liver CSCs and drives liver oncogenesis, offering a potential new target for HCC therapy. The EMBO JournalYanying Wang et al to promote BMPR1A expression and activates BMP signaling for increasing self-renewal of liver CSCs. Moreover, the addition of ASOs of HAND2-AS1 along with siRNA against BMPR1A has potent therapeutic effect on HCC.

Pancreatitis is a type of inflammation in the pancreas, which frequently occurs due to alcohol and gallstones. The present study aimed to identify pancreatitis-associated microRNAs (miRNAs) by analyzing the microarray of GSE24279. GSE24279 was downloaded from the Gene Expression Omnibus, composed of a collective of 27 pancreatitis and 22 normal control samples. The differentially expressed miRNAs (DE-miRNAs) in pancreatitis samples were screened using the Limma package in Bioconductor. Subsequently, target genes of the DE-miRNAs were predicted using the miRecords and miRWalk databases. Their potential functions were analyzed by functional and pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery online tool. Finally, pancreatitis-associated genes among the target genes identified were searched using the Comparative Toxicogenomics Database, and a regulatory network of pancreatitis-associated genes and their target miRNAs were constructed using Cytoscape software. A total 14 upregulated and 39 downregulated miRNAs were identified in pancreatitis samples compared with control samples and 290 target genes of DE-miRNAs were determined. Cyclin D1 (CCND1), v-akt murine thymoma viral oncogene homolog 2 (AKT2), cyclin-dependent kinase 6 (CDK6) and SMAD family member 2 (SMAD2) were involved in the pathway of pancreatic cancer. Among the target genes, 279 genes were pancreatitis-associated genes, which in turn were targeted by 37 miRNAs in the regulatory network. Hsa-miR-15a, hsa-miR-16, hsa-miR-155, hsa-miR-375 and hsa-miR-429 in particular may be involved in pancreatitis by targeting genes in the regulatory network, including hsa-miR-15a→CCND1, hsa-miR-16→CCND1, hsa-miR-155→CCND1/SMAD2, hsa-miR-375→AKT2/CDK6 and hsa-miR-429→CCND1. The above miRNAs and their targets may contribute to the pathogenesis of pancreatitis; therefore, they may be potential therapeutic targets.

AIMTo explore the value of three-dimensional (3D) visualization technology in the minimally invasive treatment for infected necrotizing pancreatitis (INP).METHODSClinical data of 18 patients with INP, who were admitted to the PLA General Hospital in 2017, were retrospectively analyzed. Two-dimensional images of computed tomography were converted into 3D images based on 3D visualization technology. The size, number, shape and position of lesions and their relationship with major abdominal vasculature were well displayed. Also, percutaneous catheter drainage (PCD) number and puncture paths were designed through virtual surgery (percutaneous nephroscopic necrosectomy) based on the principle of maximum removal of infected necrosis conveniently.RESULTSAbdominal 3D visualization images of all the patients were well reconstructed, and the optimal PCD puncture paths were well designed. Infected necrosis was conveniently removed in abundance using a nephroscope during the following surgery, and the median operation time was 102 (102 ± 20.7) min. Only 1 patient underwent endoscopic necrosectomy because of residual necrosis.CONCLUSIONThe 3D visualization technology could optimize the PCD puncture paths, improving the drainage effect in patients with INP. Moreover, it significantly increased the efficiency of necrosectomy through the rigid nephroscope. As a result, it decreased operation times and improved the prognosis.

Background: Persistent external pancreatic fistula (EPF) in patients with pancreatic duct disruption or disconnection can result from minimal access to retroperitoneal pancreatic necrosectomy (MARPN) in severe acute pancreatitis patients, which is a difficult problem for clinicians and requires a long treatment duration. This study aimed to investigate the effectiveness and safety of trans-sinus gastric stent placement and drainage using interventional technology in the management of persistent EPF after MARPN in severe acute pancreatitis.Methods: From August 2018 to December 2020, the data of 9 patients with persistent EPF treated with trans-sinus gastric stent placement and drainage in our hospital were retrospectively collected. The main outcome measures were technical success rate, recurrence rate, new pancreatic fluid collection, morbidity, and mortality. All patients were followed up after the procedure through clinic visits and imaging modalities.Results: The median age of the patients was 46 years (30-61 years). The median persistent EPF duration was 5 months (2-12 months). The median follow-up time was 41 months (range, 20-47 months). The median operation time was 48 minutes (range, 40-54 minutes), and the technical success rate was 100%. Seven days after treatment, the percutaneous drainage tubes of all patients were removed. Six months after the procedure, 2 patients lost the stents, and one of those patients suffered from a pseudocyst, which gradually increased to a maximum diameter of 7 cm over 9 months. Therefore, a double pigtail drainage tube was placed under the guidance of an endoscope. The second of these 2 patients had no recurrence or pseudocyst. Twelve months after the procedure, another 3 patients lost the stents; 18 months after the procedure, another 2 patients lost the stents. These patients had no recurrence as well. No other adverse events or deaths occurred during the study period. Conclusion:Trans-sinus tract gastric stent placement and drainage are safe and effective in the treatment of persistent EPF after MARPN in severe acute pancreatitis patients. However, this study had a small sample size and did not include a comparative group.