Prospective observational study of baloxavir marboxil in adults and adolescents with uncomplicated influenza from China.

Introduction: There are limited data on the efficacy of baloxavir marboxil (baloxavir) versus oseltamivir in Chinese patients with influenza A. Methods: This study is an observational real-world investigation encompassing 246 patients (baloxavir, n = 147; oseltamivir, n = 99) confirmed positive for influenza A. The choice between baloxavir and oseltamivir antiviral treatments was determined collaboratively by the clinician and the patient. A thorough comparative analysis was undertaken between the two groups, examining parameters such as the duration of fever and symptoms, viral load dynamics, lymphocyte changes, and enhancements in health-related quality of life (QoL). Results: No significant differences were observed in demographic data between the two groups. The duration of fever was significantly shorter in the baloxavir group (P < 0.001). However, the duration of symptoms was not significant different (P = 0.167). Multivariable Cox analysis showed the independent factors affecting duration of fever were baloxavir treatment (HR = 2.033, P < 0.001), fever on day 1 (HR = 0.741, P = 0.010) and CRP level (HR = 1.009, P = 0.039). Moreover, sex (HR= 0.660, P = 0.019) and monocyte count (HR = 1.355, P = 0.018) were independent factors affecting the duration of symptoms. No significant difference in change of health-related quality of life (P > 0.05), positive rate of viral antigen on day 3 (P = 0.477) between the two groups. Remarkably, a mutation was observed in one case on the third-day after baloxavir treatment compared with first-day, from cysteine to serine at position 384 of the PA subunit. Conclusion: In the clinical setting, baloxavir demonstrated comparable clinical benefits to oseltamivir, establishing its efficacy as an effective antiviral therapy for Chinese patients with influenza.

IGF2BP3-NRF2 axis regulates ferroptosis in hepatocellular carcinoma.

Poor sensitivity to sorafenib has been an important constraint on the efficacy of targeted therapy in advanced hepatocellular carcinoma (HCC). Therefore, it is particularly important to explore effective therapeutic targets to improve the sensitivity of HCC cells to sorafenib. Upregulation of IGF2BP3 is strongly associated with tumor invasion, early recurrence and poor prognosis in various human cancers, including HCC, but its roles in the sorafenib treatment of HCC remain unclear. In our study, IGF2BP3 knock-down significantly promoted ferroptosis in HCC cells through the evaluation of the Reactive Oxygen Species (ROS), Fe2+ and malondialdehyde (MDA) levels after sorafenib administration. In addition, NRF2 mRNA was identified as an important target of IGF2BP3 by bioinformatics analysis, RNA binding protein immunoprecipitation (RIP) and RNA pulldown experiments. More importantly, IGF2BP3, as an m6A (N6-Methyladenosine) reader, was shown to promote the stability of NRF2 mRNA by reading its m6A modification. Similar results were obtained from in vivo experiments. In summary, our study uncovered the role of IGF2BP3-NRF2 axis on ferroptosis in HCC, providing significant evidence for new anti-cancer strategies aimed at improving the efficacy of sorafenib.

KIAA1522 is a new biomarker of promoting the tumorigenesis and distant metastasis of colorectal carcinoma.

PURPOSE: Our research was absorbed into exploring the expression, clinicopathological value, biological significance and signaling pathway of KIAA1522 in colorectal carcinoma and its distant metastasis. MATERIALS AND METHODS: The expression of KIAA1522 and survival analysis in colorectal carcinoma (CRC) were assessed using GEPIA databases. Then we evaluated the expression of KIAA1522 immunohistochemically in tissue samples of 57 patients with colorectal carcinoma liver metastasis (CRLM). The correlations between the expression of KIAA1522, clinical significance and prognosis of these 57 patients with CRLM were analyzed. The migration and invasion of KIAA1522 were explored by western blotting, CCK-8, colony formation, flow cytometry, wound healing assays and transwell invasion in vitro and tail vein injection models in vivo. Then, transcriptome sequencing and gene set enrichment analysis was performed to identify the signaling pathways involved, while western blotting analysis and immunohistochemistry (IHC) were used to identify the expression of key genes in Notch signaling. RESULTS: KIAA1522 was overexpressed in CRLM tissues and colon cancer cell lines, and the expression of KIAA1522 in metastatic sites was positively correlated with that in primary sites. In addition, the overexpression of KIAA1522 is associated with poor clinicopathological features. Survival analysis showed that the overexpression of KIAA1522 predicted a low overall survival rate in patients with CRLM. Functional studies suggested that KIAA1522 promotes the proliferation, invasion and migration of colon carcinoma in vitro. KIAA1522 could promote distant metastasis of CRC in vivo. Moreover, KIAA1522 upregulated the Notch signaling pathway in colorectal cancer cell lines in vitro and lung metastatic nodes in vivo. CONCLUSION: In conclusion, it is suggested that the upregulation of KIAA1522 might promote the tumorigenicity and metastasis of colorectal carcinoma through Notch signaling pathway. KIAA1522 plays a carcinogenic role in the metastasis of colorectal carcinoma and might serve as a new molecular target for the treatment.

ST8SIA6-AS1 promotes the development of hepatocellular carcinoma cells through miR-338-3p/NONO Axis.

BACKGROUND: Increasing studies have shown a vital fact that long non-coding RNAs (lncRNAs) play a considerable regulatory role in hepatocellular carcinoma (HCC) progression. However, whether ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sialyltransferase 6 antisense RNA 1 (ST8SIA6-AS1) affects the development of HCC is unclear. METHODS: The target genes in HCC cell lines were quantified via utilzing quantitative real-time polymerase chain reaction (RT-qPCR) analysis and western blot. Effects of ST8SIA6-AS1 on proliferative, apoptosis and migratory ability of HCC cells were proved by a series of function experiments. The cellular distribution of ST8SIA6-AS1 was examined through fluorescent in situ hybridization (FISH) assay and subcellular fractionation experiments. RNA pulldown assay was implemented to explore the target of ST8SIA6-AS1. RNA Binding Protein Immunoprecipitation (RIP) and luciferase reporter assays were performed to identify the specific relationships between miR-338-3p and ST8SIA6-AS1/ non-POU domain containing octamer binding (NONO). RESULTS: The expression of ST8SIA6-AS1 was apparently elevated in HCC cell. Silenced ST8SIA6-AS1 reduced proliferative, migratory and invasive ability of HCC cells. Moreover, ST8SIA6-AS1 targeted miR-338-3p to modulate the expression of NONO in HCC cells. CONCLUSIONS: ST8SIA6-AS1 enhances the progression of HCC via miR-338-3p/NONO axis in vitro.

Migration of hem-o-lock clips and stitches into the duodenum after laparoscopic hepatectomy and cholecystectomy: A case report.

RATIONALE: Migration of endoclips and stitches into the duodenum after laparoscopic hepatectomy is incredibly rare with a poorly understood mechanism. PATIENT CONCERNS: A 56-year-old woman who underwent laparoscopic left hepatectomy and cholecystectomy in August 2016 was admitted to our hospital with nausea and vomiting in December 2017. DIAGNOSES: Abdominal computed tomography (CT) scan showed high density shades in duodenal ampulla. Esophagogastroduodenoscopy showed deformation of the duodenal ampulla into two lumens; hem-o-lock clips and stitches were detected in the upper lumen. Contrast enhanced CT scan revealed gastric cancer with liver metastasis (GCLM). INTERVENTIONS: The hem-o-lock clips and stitches were present in the wall of the duodenum; therefore, no attempt was made to remove them. High quality liquid diet, partial parenteral nutrition, and chemotherapy were administered to the patient. OUTCOMES: In September 2018, the patient died of hepatic failure caused by GCLM. LESSONS: This rare complication of the migration of endoclips and stitches into the duodenum after laparoscopic hepatectomy can cause epigastric pain and duodenal obstruction. The complication could be potentially avoided using absorbable endoclips and stitches or by performing of ultrasonic dissection by a skilled operator.

Pancreatogenic choledocholithiasis in common bile duct stump after Roux-en-Y hepaticojejunostomy: A case report.

RATIONALE: Choledocholithiasis in common bile duct (CBD) stump after Roux-en-Y hepaticojejunostomy (RYHJ) is incredibly rare and its pathophysiology is poorly understood. PATIENT CONCERNS: A 79-year-old woman was admitted to our hospital with upper abdominal pain radiating through to the back in November 2016. DIAGNOSES: Abdominal computed tomography (CT) scan and magnetic resonance cholangiopancreatography (MRCP) revealed filling defects in CBD stump, chronic pancreatitis, and dilatation of CBD stump and main pancreatic duct (MPD). INTERVENTIONS: During the endoscopic retrograde cholangiopancreatography (ERCP), cannulation proceeded easily from MPD to CBD through a variant pancreatic duct, and then white crushed stones extracted from the CBD stump. Elemental analysis and infrared spectrophotometry demonstrated that the main constituent of the calculi was calcium carbonate. OUTCOMES: After a therapeutic ERCP, the patient's symptoms disappeared, and a 9-month follow-up indicated no remaining stones or lithiasis relapse. LESSONS: This type of choledocholithiasis in CBD stump after RYHJ has never been reported before. We nominated it as "pancreatogenic choledocholithiasis," and pancreatobiliary reflux caused by a variant pancreatic duct may be the main cause.

MicroRNA-199b-5p attenuates TGF-ß1-induced epithelial-mesenchymal transition in hepatocellular carcinoma.

BACKGROUND: Accumulating evidence indicates that N-cadherin is a cell adhesion molecule that has critical roles in tumour progression. However, the role of N-cadherin in hepatocellular carcinoma (HCC) remains controversial. METHODS: This study aims to investigate the expression status of N-cadherin and its molecular mechanisms in HCC. RESULTS: The expression of N-cadherin was markedly overexpressed in HCC tissues and cell lines. We identified that miR-199b-5p binds to the 3'-UTR of N-cadherin mRNA, thus decreasing N-cadherin expression in HCC cells. We also found the downregulation of miR-199b-5p in HCC specimens, which was inversely correlated with N-cadherin upregulation, predicted poor clinical outcomes in HCC patients. Next, we determined that miR-199b-5p overexpression promoted cell aggregation, suppressed cell migration and invasion in HCC cells, and inhibited xenografts tumour metastasis in nude mice. Moreover, we demonstrated that miR-199b-5p attenuated TGF-ß1 induced epithelial-mesenchymal transition (EMT) -associated traits, while its effects could be partially reversed by N-cadherin restoration. Finally, we examined that N-cadherin downregulation or miR-199b-5p overexpression suppressed TGF-ß1-induced Akt phosphorylation, and inhibition of PI3K/Akt pathway blocked TGF-ß1-induced N-cadherin overexpression in HCC cells. CONCLUSIONS: Our data demonstrate that N-Cadherin was markedly overexpressed and miR-199b-5p was significantly downregulated in HCC. MiR-199b-5p exerts inhibitory effects on EMT, and directly targets N-cadherin in HCC, supporting the potential utility of miR-199b-5p as a promising strategy to treat HCC. Also, a positive regulatory loop exists between N-cadherin and Akt signalling represents a novel mechanism of TGF-ß1-mediated EMT in HCC cells.