Kruppel-like factor 9 inhibits growth and metastasis of cholangiocarcinoma cells by targeted regulation of metallothionein 1 M transcription.

This study is to investigate the effect of Kruppel-like factor 9 (KLF9) on the occurrence and progression of cholangiocarcinoma (CCA) and its underlying mechanism. After the CCA cells were transfected with OE-KLF9 and/or sh-metallothionein 1 M (sh-MT1M), KLF9 and MT1M expression levels were measured. Likewise, the biological characteristics of CCA cells were measured, followed by detections of caspase3 activity and epithelial mesenchymal transition (EMT)-related protein. Furthermore, the binding site of KLF9 and MT1M was predicted and verified. An in vivo model of CCA in nude mice was established where tumor volume and weight were recorded, in addition to tumor metastasis in the liver. The expression of KLF9 and MT1M in the CCA cells was remarkably lower. CCA cells overexpressing KLF9 showed repressed abilities to proliferate, invade, and migrate, and strengthened cell apoptosis. KLF9 inhibited EMT, growth, and migration of CCA cells by modulating MT1M transcription. Additionally, KLF9 facilitated MT1M expression in vivo and improve the progression of CCA in nude mice. KLF9 acted as a transcription factor of MT1M to promote its transcription level, thereby affecting the growth and migration of CCA cells, and ultimately improving the occurrence and development of CCA.

Short-Term and Long-Term Curative Effect of Partial Hepatectomy on Ruptured Hemorrhage of Primary Liver Cancer after TAE.

Objective: To observe the short-term and long-term curative effects of partial hepatectomy on ruptured hemorrhage of primary liver cancer after transcatheter arterial embolization (TAE). Methods: A total of 150 patients with primary liver cancer treated in the hospital were enrolled as research objects between February 2018 and February 2021, including 75 cases undergoing TAE in the TAE group and the other 75 cases undergoing elective partial hepatectomy after TAE in the combination group. The surgical related indexes (leaving bed time, discharge time, success rate of hemostasis, lesion clearance rate), mean arterial pressure (MAP), heart rate (HR), hemoglobin, and liver function indexes (serum alpha-fetoprotein (AFP), albumin (ALB), total bilirubin (TBIL)) before and after treatment, postoperative complications, survival rate, and recurrence rate at 1 year after surgery between the two groups were compared. Results: Compared with the TAE group, hospitalization time was shorter (P < 0.05), the success rate of hemostasis and lesions clearance rate were higher in the combination group (P < 0.05). After surgery, levels of HR and serum AFP were significantly decreased, while levels of MAP, hemoglobin, serum ALB, and TBIL were significantly increased in both groups. The levels of HR and serum AFP in the combination group were lower than those in the TAE group, while levels of MAP, hemoglobin, serum ALB, and TBIL were higher than those in the TAE group (P < 0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P < 0.05). Compared with the TAE group, the recurrence rate was lower, and the survival rate was higher in the combination group at 1 year after surgery (P < 0.05). Conclusion: Partial hepatectomy can effectively improve hemostatic effect and liver function in ruptured hemorrhage of primary liver cancer after TAE, increase survival rate, and reduce postoperative recurrence rate.

Real-world use of nonvitamin K antagonist oral anticoagulant in atrial fibrillation patients with liver disease: A meta-analysis.

Several studies have investigated the effectiveness and safety of nonvitamin K antagonist oral anticoagulants (NOACs) vs vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and liver disease. Herein, we conducted a meta-analysis to compare the effect of NOACs with VKAs in patients with AF and liver disease. We also conducted a subsidiary analysis to compare the risk of liver injury between NOACs and VKA in AF patients. We systematically searched the PubMed and Embase databases from January 2009 to May 2020 for the relevant studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were selected and pooled using a random-effects model. A total of six cohorts were included. Compared with VKA use, the use of NOACs was associated with reduced risks of stroke or systemic embolism (HR 0.68, 95% CI 0.49-0.93), all-cause death (HR 0.69, 95% CI 0.63-0.75), and intracranial bleeding (HR 0.49, 95% CI 0.40-0.59), whereas the outcomes of major bleeding (HR 0.72, 95% CI 0.51-1.01) and gastrointestinal bleeding (HR 0.84, 95% CI 0.51-1.36) were not significantly different between groups in AF patients with liver disease. Moreover, compared with VKA use, the use of NOACs was associated with a reduced risk of liver injury (HR 0.72, 95% CI 0.61-0.84) in AF patients. Compared with VKAs, the use of NOACs was associated with reduced risks of stroke or systemic embolism, all-cause death, and intracranial bleeding in AF patients with liver disease, and associated with a reduced risk of liver injury in AF patients.

A novel epigenetic signature to predict recurrence-free survival in patients with colon cancer.

BACKGROUND: DNA methylation plays an important role in the initiation and progression of colon cancer. The aim of the present study was to perform a comprehensive analysis of DNA methylation and gene expression profiles in order to develop a signature to predict recurrence-free survival (RFS) of colon cancer. METHODS: DNA methylation and mRNA expression data were obtained from TCGA database, and were analyzed using an R package MethylMix. Functional enrichment analysis was performed on statistically significant genes identified by MethylMix criteria. The epigenetic signature and nomogram associated with the RFS of colon cancer were established by the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. Additionally, a joint survival analysis of gene expression and methylation was performed to identify potential prognostic factors for patients with colon cancer. RESULTS: A total of 179 differentially methylated genes were obtained using MethylMix algorithm. An epigenetic signature for RFS was developed using LASSO. Patients with high-risk had significantly worse RFS than those with low-risk. The signature is independent of clinicopathological variables and indicated better predictive power than other clinicopathological variables in patients with colon cancer. Moreover, joint survival analysis of gene expression and methylation revealed that seven methylated genes could be independent prognostic factors for RFS in colon cancer. CONCLUSIONS: Our proposed epigenetic signature presents potential prognostic significance in assessing recurrence risk stratification for patients with colon cancer.

The enhanced recovery after surgery (ERAS) program in liver surgery: a meta-analysis of randomized controlled trials.

The enhanced recovery after surgery (ERAS) program aims to attenuate the surgical stress response and decrease postoperative complications. It has increasingly replaced conventional approaches in surgical care. To evaluate the benefits and harms of the ERAS program compared to conventional care in patients undergoing liver surgery. We searched the MEDLINE, PubMed, EMBASE and Cochrane databases. All RCTs that compared the ERAS program with conventional care were selected. Four RCTs were eligible for analysis, which included 634 patients (309 ERAS vs. 325 conventional). Overall morbidity (RR 0.67; 95 % CI 0.48-0.92; p = 0.01), primary length of stay (WMD -2.71; 95 % CI -3.43 to -1.99; p < 0.00001), total length of stay (WMD -2.10; 95 % CI -3.96 to -0.24; p = 0.03), time of functional recovery (WMD -2.30; 95 % CI -3.77 to -0.83; p = 0.002), and time to first flatus (SMD, -0.52; 95 % CI -0.69 to -0.35; p < 0.00001) were significantly shortened in the ERAS group. Quality of life was also better in the ERAS group. However, no significant differences were noted in mortality, readmission rates, operative time and intraoperative blood loss. The ERAS Program for liver surgery significantly reduced overall morbidity rates, accelerated functional recovery, and shortened the primary and total hospital stay without compromising readmission rates. Therefore, ERAS appears to be safe and effective. However, the conclusions are limited because of the low methodological quality of the analyzed studies. Further studies are needed to provide more solid evidence.

Long noncoding RNA GAS5 can predict metastasis and poor prognosis: a meta-analysis.

INTRODUCTION: Growth arrest-specific 5 (GAS5), a newly discovered long-noncoding RNAs (lncRNAs), has been reported to be down-regulated in multiple cancers. This meta-analysis aims to identify the potential value of GAS5 as a biomarker of cancer metastasis and prognosis. EVIDENCE ACQUISITION: We searched the MEDLINE, EMBASE and Cochrane Library databases. This meta-analysis collected all relevant studies and explored the association of lncRNA GAS5 with overall survival (OS), lymphnode metastasis (LNM), and distant metastasis (DM). EVIDENCE SYNTHESIS: Four studies were eligible for analysis, which included 328 patients. Meta-analysis revealed that low levels of GAS5 expression could predict poor OS in multiple cancers (pooled Hazard Ratio [HR]: 0.38, 95% confidence interval [CI]: 0.26-0.54, P<0.00001). Moreover, compared with high GAS5 expression, low GAS5 expression was correlated with LNM (pooled HR: 4.03, 95% CI: 1.93-8.41, P=0.0002) and DM (pooled HR: 10.17, 95% CI: 1.26-82.31, P=0.03). CONCLUSIONS: lncRNA GAS5 may potentially serve as a novel biomarker for cancer metastasis and prognosis.