Circular RNA (circRNA), a type of non-coding RNA, can promote or suppress tumorigenesis. To investigate the involvement of circRNA in diffuse large B-cell lymphoma (DLBCL), we performed a circRNA microarray analysis on paired DLBCL and normal tissues. We identified a novel and highly stable circRNA originating from the back-splicing of APC exon 7 to exon 14, circ-APC (hsa_circ_0127621), which was downregulated in DLBCL tissues, cell lines and plasma. In gain-of-function experiments, ectopic expression of circ-APC inhibited DLBCL cell proliferation in vitro and tumor growth in vivo. Cytoplasmic circ-APC functioned as a sponge for miR-888, thus post-transcriptionally upregulating APC by alleviating the repressive effects of miR-888 on this gene. Further, nuclear circ-APC bound to the APC promoter and recruited the DNA demethylase TET1, thereby transcriptionally upregulating APC. Upon its upregulation, APC dampened the canonical Wnt/β-catenin signaling pathway by reducing the accumulation of β-catenin in the nucleus, thereby retarding DLBCL growth. Clinically, circ-APC was found to be an effective diagnostic and prognostic biomarker for patients with DLBCL. Our study suggests that circ-APC is a novel proliferation inhibitor, and that restoring circ-APC expression may be a promising therapeutic approach for DLBCL patients.

Cerebral venous sinus thrombosis (CVST) is an uncommon subtype of stroke with highly variable clinical presentation. Although anticoagulation with heparin and/or warfarin remains the standard treatment for CVST, treatment failure is still common. This study aims to evaluate the safety and efficacy of Batroxobin in combination with anticoagulation on CVST control. In this retrospective study, a total of 61 CVST patients were enrolled and divided into Batroxobin (n = 23) and control (n = 38) groups. In addition to the same standard anticoagulation in control, patients in the treatment group received Batroxobin 5 BU intravenous infusion (10 BU for the first time) every other day, for a total of three infusions. A higher recanalization rate was found in Batroxobin group (adjusted OR [95% CI] of 2.5 [1.1-5.0], p = 0.028) compared to the control group, especially in patients with high levels of fibrinogen (adjusted OR [95% CI] of 4.7 [1.4-16.7], p = 0.015). Statistically significant differences between the two groups were seen regarding the levels of thrombin time, fibrinogen and D-dimer at each cut-off time point (all p < 0.01). Compared with baseline, NIHSS scores at discharge showed significant improvement in the Batroxobin group [0(0, 4.25)-5(2, 11), p = 0.036]. No significant difference in mRS scores was found between the two groups at discharge or at 6-month outpatient follow-up (all p > 0.05). Additionally, Batroxobin did not increase the risk of intracranial hemorrhage. We conclude that Batroxobin is a potentially safe and effective adjunct therapeutic agent promoting CVST recanalization especially in patients with high level of fibrinogen.

The objective is to explore the effective of baseline serum neuron specific enolase (NSE) on predicting the severity and outcome in patients with cerebral venous thrombosis (CVT). A total of 156 patients confirmed as CVT in Xuanwu Hospital were enrolled in this retrospective study from March 2011 through September 2016. The severity was evaluated with the National Institutes of Health Stroke Score (NIHSS), intracranial pressure (ICP), and CVT-related complications; the outcome was evaluated by modified Rankin Scale (mRS); the relationship between baseline serum NSE and mRS was analyzed with receiver operating characteristic curve (ROC), logistic regression analysis, and Kaplan-Meier curves. Baseline level of serum NSE was positively associated with baseline NIHSS (r = 0.322, p < 0.001). Among which, patients with high level of serum NSE were also noticed with cerebral venous infarction (p < 0.001), intracranial hemorrhage (p < 0.001), seizure (p = 0.035). Meanwhile, patients in NSE ≥ 15.05 ng/mL group vs. NSE < 15.05 ng/mL group had large mRS scores (≥ 3) at discharge (adjusted OR: 5.40, 95% CI 1.27-22.91; p = 0.022) and higher percentage of mRS scores ≥ 3 during 40 months of outpatient follow-up (log-rank p < 0.001). Baseline level of serum NSE is positively associated with the severity of CVT. Presumably NSE may be a potential predictor for the clinical outcome of CVT.