m6A methylation-mediated regulation of LncRNA MEG3 suppresses ovarian cancer progression through miR-885-5p and the VASH1 pathway.

BACKGROUND: Ovarian cancer poses a serious threat to women's health. Due to the difficulty of early detection, most patients are diagnosed with advanced-stage disease or peritoneal metastasis. We found that LncRNA MEG3 is a novel tumor suppressor, but its role in tumor occurrence and development is still unclear. METHODS: We investigated the expression level of MEG3 in pan-cancer through bioinformatics analysis, especially in gynecological tumors. Function assays were used to detect the effect of MEG3 on the malignant phenotype of ovarian cancer. RIP, RNA pull-down, MeRIP-qPCR, actinomycin D test were carried out to explore the m6A methylation-mediated regulation on MEG3. Luciferase reporter gene assay, PCR and Western blot were implemented to reveal the potential mechanism of MEG3. We further confirmed the influence of MEG3 on tumor growth in vivo by orthotopic xenograft models and IHC assay. RESULTS: In this study, we discovered that MEG3 was downregulated in various cancers, with the most apparent downregulation in ovarian cancer. MEG3 inhibited the proliferation, migration, and invasion of ovarian cancer cells. Overexpression of MEG3 suppressed the degradation of VASH1 by negatively regulating miR-885-5p, inhibiting the ovarian cancer malignant phenotype. Furthermore, we demonstrated that MEG3 was regulated at the posttranscriptional level. YTHDF2 facilitated MEG3 decay by recognizing METTL3­mediated m6A modification. Compared with those injected with vector control cells, mice injected with MEG3 knockdown cells showed larger tumor volumes and faster growth rates. CONCLUSION: We demonstrated that MEG3 is influenced by METTL3/YTHDF2 methylation and restrains ovarian cancer proliferation and metastasis by binding miR-885-5p to increase VASH1 expression. MEG3 is expected to become a therapeutic target for ovarian cancer.

Simultaneous Stenting for Symptomatic Tandem Extracranial and Intracranial Posterior Circulation Stenoses: Long-Term Outcomes and Procedural Experience.

Few studies have reported on simultaneous endovascular stenting for tandem posterior circulation (PC) stenoses and its long-term outcomes. Thus, our aim was to investigate the safety and efficacy of simultaneous stenting in patients with symptomatic tandem extra- and intracranial PC stenoses. From September 2014 to June 2018, 16 such patients with symptomatic stenoses who underwent simultaneous stent placement were analyzed. The primary outcome was occurrence of any stroke, TIA, or death within 30 days after the procedure. The secondary outcomes were technical success, clinical success, and the occurrence of in-stent restenosis ≥50% during follow-up. Technical success was defined as stent coverage of all tandem lesions and residual stenosis <30%. Clinical success was determined based on any occurrence of neurological events or death within 3 months after the procedure. All stents (19 intracranial and 14 extracranial) were placed with a technical success rate of 100%. One patient experienced a pontine ischemic stroke 2 days after the procedure and had recovered well at discharge. One patient experienced a minor complication of groin hematoma. The clinical success rate was 93.75% (15/16). During a median follow-up of 36.0 ± 11.0 months, two patients developed ISR ≥50% at the 1-year follow-up. None of the patients experienced stroke, TIA, or death after discharge during follow-up. Simultaneous stenting for symptomatic tandem extra- and intracranial PC stenoses is safe and feasible. Its impact on long-term stroke prevention is promising, and further study of a larger patient population is needed.

One-year outcomes of radiofrequency ablation of incompetent perforator veins using the radiofrequency stylet device: Cohort study from East Asia.

OBJECTIVES: The present study was designed to assess outcomes of patients undergone radiofrequency ablation (RFA) for their incompetent perforator veins (IPVs) with ClosureFast stylets. METHODS: Data of 165 IPVs in 138 limbs of 117 consecutive patients between July 2017 to Nov. 2019 were retrospectively reviewed. Primary endpoints (technical success rate, complications) and secondary endpoints (VCSS) were analyzed. RESULTS: The immediate technical success rate was 100%. There were no major complications. The rate of ecchymosis and induration was 5.8%. 129/165 IPVs in 79.5% (93/117) patients had achieved sonographic evaluation at 1 year followed-up, in which 3 perforators were recanalized. VCSS scores at pre-operation and 1-year follow-up were 5.77 ± 1.88 and 2.70 ± 1.39, respectively (t= 29.644, P= .000). CONCLUSIONS: In conclusion, RFA is safe and effective for the treatment of IPVs. At the 1-year follow-up, the RFA of IPVs showed a low recanalization rate and had a satisfactory improvement on VCSS.

Serum level of transforming growth factor beta 1 is associated with left atrial voltage in patients with chronic atrial fibrillation.

BACKGROUND: Atrial tissue fibrosis can cause electrical or structural remodeling in patients with atrial fibrillation. Transforming growth factor beta 1(TGF-ß1) signaling acts as a central role in fibroblast activation. In this report, we aimed to investigate the relationship between serum level of TGF-ß1 and mean left atrial voltage in patients with chronic atrial fibrillation (CAF). METHODS: A total of 16 consecutive adult patients with CAF who underwent catheter ablation were enrolled. Blood samples for measurement of TGF-ß1 were collected from periphery veins and coronary sinus before pulmonary vein isolation. The measurement was performed with a commercially available ELISA kit. Cardiac indices were measured using echocardiography. The left atrial electroanatomic mapping was performed after pulmonary vein isolation. RESULTS: Serum level of TGF-ß1 in peripheral blood was higher than that in coronary sinus (p < 0.001). TGF-ß1 serum level in coronary sinus negatively correlated with mean left atrial voltage (r = -0.650, p = 0.012), While periphery TGF-ß1 level tended to be negatively correlated with mean left atrial voltage(r = -0.492, p = 0.053). Patients who treated with angiotensin II receptor antagonists had lower coronary sinus TGF-ß1 serum level than those who did not treated with angiotensin II receptor antagonists (p = 0.046). CONCLUSION: Level of TGF-ß1 in peripheral serum is higher than that in coronary sinus, and serum level of TGF-ß1 in coronary sinus is negatively associated with mean left atrial voltage in patients with CAF, angiotensin II receptor antagonists could affect TGF-ß1 serum level.