Implant modification by HF acid etching and anodization to form a hierarchical micro/nanotextured surface could improve titanium implant osseointegration in OVX sheep 12 weeks after implantation.
Background: Hemorrhoids are a frequently-occurring disease of the anorectal system that is often accompanied by vascular hyperplasia and edema. A METTL14-mediated RNA N-6 methyladenosine (m6A) modification can improve mRNA stability and increase its transcriptional and translational activities, closely related to the occurrence of many diseases.Methods: Western blot, qPCR, and immunofluorescence staining were used to detect the levels of gene and protein expression. Haematoxylin and eosin staining was used for histopathological examination. RNA immunoprecipitation-PCR and RNA dot blotting were used to detect mRNA m6A modification.Results: Obvious signs of angiogenesis (CD31+/vWF+) were identified in the hemorrhoids. High levels of METTL14 expression on vascular endothelial cells (CD31+) suggested that angiogenesis was accompanied by differential modification of m6A RNA. It was subsequently found that the level of miR-4729 expression was significantly decreased in hemorrhoid tissues. The luciferase reporter enzyme assay results suggested that miR-4729 silenced its expression by targeting the 3'UTR of METTL14 mRNA. MiR-4729 overexpression in human umbilical vein endothelial cells (HUVECs) inhibited the proliferation and migration of HUVECs in vitro and vascular structure formation in the outer matrix. MiR-4729 overexpression significantly inhibited endogenous METTL14 expression in HUVECs and reduced the entire m6A RNA modification, especially the level of m6A methylation at the specific site of the 3' UTR of TIE1 mRNA. Moreover, miR-4729 overexpression significantly inhibited the molecular loop of the TIE1/VEGFA signaling pathway in HUVECs.Conclusions: Our findings confirmed that the down-regulation of miR-4729 in hemorrhoid vascular endothelial cells was one of the main reasons for vascular proliferation. The overexpression of miR-4729 in vascular endothelial cells decreased the global mRNA methylation and TIE1 mRNA 3'UTR-specific site methylation by silencing METTL14 expression, reducing TIE1 mRNA stability, down-regulating the TIE1/ VEGFA signal molecular loop expression, and weakening angiogenesis ability.
IntroductionPostoperative recurrence and related complications are common and related to poor outcomes in patients with anal fistula (AF). Due to being associated with short-term and long-term cure rates, perioperative complications have received widespread attention following AF surgery. This study aims to identify a set of predictive factors to develop risk prediction models for recurrence and related complications following AF surgery. We plan to develop and validate risk prediction models, using information collected through a WeChat patient-reported questionnaire system combined with clinical, laboratory and imaging findings from the perioperative period until 3–6 months following AF surgery.Methods and analysisThis is a prospective hospital-based cohort study using a linked database of collected health data as well as the follow-up outcomes for all adult patients who suffered from AF at a tertiary referral hospital in Shanghai, China. We will perform logistic regression models to predict anal fistula recurrence (AFR) as well as related complications (eg, wound haemorrhage, faecal impaction, urinary retention, delayed wound healing and unplanned hospitalisation) during and after AF surgery, and machine learning approaches will also be applied to develop risk prediction models. This prospective study aims to develop the first risk prediction models for AFR and related complications using multidimensional variables. These tools can be used to warn, motivate and empower patients to avoid some modifiable risk factors to prevent postoperative complications early. This study will also provide alternative tools for the early screening of high-risk patients with AFR and related complications, helping surgeons better understand the aetiology and outcomes of AF in an earlier stage.Ethics and disseminationThe study was approved by the Institutional Review Board of Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine (approval number: 2019-699-54-01). The results of this study will be submitted to international scientific peer-reviewed journals or conferences in surgery, anorectal surgery or anorectal diseases.Trial registration numberChiCTR1900025069; Pre-results.
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