Although the dysregulation of bile acid (BA) composition has been associated with fibrosis progression, its precise roles in liver fibrosis is poorly understood. This study demonstrates that solute carrier family 27 member 5 (SLC27A5), an enzyme involved in BAs metabolism, is substantially downregulated in the liver tissues of patients with cirrhosis and fibrosis mouse models. The downregulation of SLC27A5 depends on RUNX family transcription factor 2 (RUNX2), which serves as a transcriptional repressor. The findings reveal that experimental SLC27A5 knockout (Slc27a5^−/−) mice display spontaneous liver fibrosis after 24 months. The loss of SLC27A5 aggravates liver fibrosis induced by carbon tetrachloride (CCI₄) and thioacetamide (TAA). Mechanistically, SLC27A5 deficiency results in the accumulation of unconjugated BA, particularly cholic acid (CA), in the liver. This accumulation leads to the activation of hepatic stellate cells (HSCs) by upregulated expression of early growth response protein 3 (EGR3). The re‐expression of hepatic SLC27A5 by an adeno‐associated virus or the reduction of CA levels in the liver using A4250, an apical sodium‐dependent bile acid transporter (ASBT) inhibitor, ameliorates liver fibrosis in Slc27a5^−/− mice. In conclusion, SLC27A5 deficiency in mice drives hepatic fibrosis through CA‐induced activation of HSCs, highlighting its significant implications for liver fibrosis treatment.

Several previous studies have confirmed that thrombocytosis was related to reduced survival in many solid tumors. However, the prognostic significance of thrombocytosis in endometrial carcinoma (EC) was still controversy. Therefore, we conducted this study to assess the prognostic value of thrombocytosis in EC. The database including PubMed, MEDLINE, EMBASE, and Web of Science was searched to explore available literature. Above all, the hazard ratio (HR), odds ratios (OR) with 95% confidence intervals (CIs) was used to investigate the correlation between thrombocytosis and overall survival (OS) and disease-free survival (DFS). Moreover, the association between thrombocytosis and patient clinicopathological characteristics was explored. Publication bias and sensitivity analysis also were conducted in this study. Overall, 11 studies involving 3439 patients were contained in this study. The results revealed that pretreatment thrombocytosis was significantly related to a decreased OS (pooled HR = 2.99; 95% CI = 2.35–3.8; P < 0.001) and DFS (pooled HR = 2.86; 95% CI = 2.27–3.6; P < 0.001) in patients with EC. Moreover, thrombocytosis was correlated with adverse clinicopathological parameters. Pretreatment thrombocytosis is an adverse prognostic marker in patients with EC.

Introduction We aimed to evaluate poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) regimens in BRCA-mutated ovarian cancer for patients responsive to front-line platinum (bevacizumab and olaparib, veliparib and chemotherapy, olaparib) or platinum-sensitive relapsed (olaparib, rucaprib, niraparib) patients in phase III randomized controlled trials. Methods A network meta-analysis was utilized to generate the direct and indirect comparisons. The primary outcomes for network meta-analysis were efficacy (hazard ratios for progression-free survival in BRCA mutation cohort) and toxicity (odds ratios for all grade 3–4 adverse events). The American Society of Clinical Oncology (ASCO) value framework was used to assess the cost-effectiveness of the PARPi regimens. Results Network meta-analysis indicated no statistically significant differences in efficacy and toxicity among the assessed upfront or relapsed PARPi regimens (95% CI included 1). The ASCO value framework indicated that current PARPi regimens were similar in clinical benefits, toxicity, and net health benefit in the upfront (bevacizumab and olaparib, veliparib and chemotherapy, olaparib) and relapsed setting (olaparib, rucaprib, niraparib). The addition of bevacizumab to olaparib ($353.72) increased the cost per unit net health benefit for patients compared with olaparib monotherapy ($260.57). The upfront PARPi regimens had lower toxic scores than the regimens used at relapse. Conclusions The choice of PARPi regimens both in the upfront and relapsed setting should consider not only efficacy and toxicity but also costs in BRCA mutation patients. Current combining PARPi regimens are not recommended for such patients in the upfront setting from the cost-effective perspective. Upfront PARPi regimens are less toxic than those used at relapse.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Dan Nie1, Lingping Zhang2, Qian Guo1 and Xiguang Mao1 1Department of Gynecology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China 2Department of Neonatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China Correspondence to: Dan Nie, email: niedan@swmu.edu.cn Keywords: high-mobility group protein A; prognosis; meta-analysis Received: July 29, 2017 Accepted: November 17, 2017 Published: December 04, 2017 ABSTRACT Overexpression of the high mobility group protein A2 (HMGA2), an architectural transcription factor, has been linked to poor prognosis in many malignancies, although this remains controversial. Herein, we conducted a meta-analysis to investigate whether HMGA2 has prognostic value, and evaluated the association between HMGA2 and clinicopathologic factors in malignancies. A total of 29 studies involving 4114 patients were included in this meta-analysis. The pooled results demonstrated that elevated HMGA2 predicted a poor overall survival (OS) (hazard ratio [HR] = 1.82; 95% confidence interval [CI] = 1.62–2.05; P < 0.001) and disease-free survival/progression-free survival/recurrence-free survival (HR = 1.94; 95% CI = 1.27–2.98; P = 0.002). Subgroup analysis conducted by study region, sample size, detection method, and analysis method indicated that HMGA2 overexpression correlated with poor OS. Furthermore, HMGA2 overexpression was found to be linked to poor OS in various cancers except ovarian cancer (pooled HR = 1.14; 95% CI = 0.62–2.09; P = 0.673). High HMGA2 expression level also correlated with advanced TNM stage (OR = 2.44; 95% CI =1.87–3.2; P < 0.001), lymphovascular invasion (OR = 2.46, 95% CI = 1.67–3.64; P < 0.001), distant metastasis (OR = 2.66; 95% CI =1.51–4.69; P < 0.001), and lymph node metastasis (OR = 1.83; 95% CI =1.27–2.64; P = 0.001). In conclusion, HMGA2 overexpression indicates a worse prognosis and may serve as a prognostic predictor in cancer patients.