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N6-Methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA, playing critical role in various bioprocesses. Like other epigenetic modifications, m6A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m6A demethylases have been reported, fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.
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BACKGOUND: Asymmetric cortical vessel sign (ACVS) on susceptibility-weighted imaging (SWI) indicates elevated concentration of deoxyhemoglobin and elevated oxygen extraction fraction in patients with cerebral ischemia. This study aimed to clarify whether ACVS is associated with impaired hemodynamics and hyperperfusion syndrome in patients with moyamoya disease (MMD). METHODS: Consecutive adult patients with MMD were enrolled. ACVS data on SWI and perfusion data using dynamic perfusion computed tomography were obtained and evaluated preoperatively and on postoperative days 2 and 180. RESULTS: A total of 24 patients with MMD were enrolled. Of 11 (45.83%) patients showing positive ACVS before surgery, 8 turned negative on postoperative day 2 and 9 showed absence of ACVS 180 days after surgery. Regions of interest showing positive ACVS had lower cerebral blood flow (CBF, P<0.001), increased cerebral blood volume (P = 0.021), prolonged time to peak (P<0.001), and mean transit time (P = 0.009). No patients with hemorrhagic symptoms showed positive ACVS(P = 0.041) and patients with positive ACVS showed more increase in CBF (P<0.004). CONCLUSIONS: In patients with MMD, ACVS on SWI indicates severe impairment in hemodynamics and is associated with more increase in CBF after bypass surgery. Hence, ACVS on SWI might be considered as a neuroimaging marker for the evaluation of hemodynamics in patients with MMD.
Subject(s)
Hemodynamics , Magnetic Resonance Imaging , Moyamoya Disease/diagnostic imaging , Neuroimaging , Tomography, X-Ray Computed , Adult , Brain Ischemia/diagnostic imaging , Brain Ischemia/etiology , Brain Ischemia/mortality , Cerebral Revascularization , Cerebrovascular Circulation , Female , Hemoglobins/analysis , Humans , Male , Moyamoya Disease/complications , Moyamoya Disease/physiopathology , Moyamoya Disease/surgery , Oxygen/analysis , Prospective Studies , Risk Factors , Young AdultABSTRACT
Objective To explore the clinical application value of second-generation dual-source CT combined with intelligent modulation and iterative reconstruction in emergency aortic dissection imaging.Methods A total of 40 emergency patients with clinical suspected aortic dissection were included in this study.Conventional scanning was performed in the control group,and large-pitch intelligent modulation and iterative reconstruction were performed in the test group.The mean CT value,mean noise,signal noise ratio(SNR),contrast noise ratio(CNR),effective dose,image quality and aortic root image quality were evaluated and analyzed.Results Totally 40 patients successfully completed CT aortic dissection imaging.There was no difference in image quality between the two groups (P> 0.05).The quality of aortic root images in the test group was better than that in the control group,and the difference was statistically significant(x2=22.556,P<0.05).The mean CT value and mean noise of aorta in the control group were slightly higher than those in the test group.However,SNR and CNR in the test group were higher than those in the control group,and the difference was statistically significant (t =-21.042,-15.924,8.530,11.495,P<0.05).The effective dose of the control group [(10.59±3.89)mSv] was significantly higher than that [(6.39±0.81) mSv] of the test group,the difference was statistically significant (t =-12.327,P<0.05).Conclusions The combined intelligent modulation technique and iterative reconstruction technique with dual-source CT large pitch scanning can meet the requirements of image quality and reduce the effective dose,and can be used as a conventional imaging method for emergency CT of aortic dissection.
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Objective To assess the value of cardiac magnetic resonance (CMR) imaging in left ventricular structure and function in patients with end stage renal disease (ESRD).Methods Twenty-five patients with ESRD and 10 healthy subjects underwent CMR.Left ventricular end diastolic volume(EDV),end-diastolic diameter(EDD),end-systolic volume(ESV),end-systolic diameter(ESD),stroke volume(SV),ejection fraction(EF),LVM and interventricular septum (IVS) thickness were measured and compared.The parameters from CMR and 2DTTE were compared.Results The EF in patients with ESRD was significantly lower than that in controls (P<0.001),while ESV,ESD,IVS and LVM were respectively higher than these in controls (P<0.05).There was no significant difference (P>0.05) in ESV between CMR and 2DTTE,but EF of CMR was significantly higher than this of 2DTTE (P<0.05).There was no significant difference (P =0.296) in left ventricular systolic functional category.Bland-Altman plots showed a good agreement between the two methods.Conclusion CMR is a helpful tool to assess left ventricular structure and function in patients with ESRD.
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Objective To identify the spatial distribution of stray radiation from mobile CT head scanning for the purpose of radiation protection.Methods The head series of CareTom mobile CT were scanned and the radiation dose was measured using TLD (LiF:Mg,Cu,P).The isodose maps of radiation dose field were plotted using Matlab software.Results Radiation dose in the front of the mobile CT was slightly higher than that in the back.The maximum value of 0.255 mGy was found to be at 0.5 m from the scanning hole center.Conclusions The stray radiation dose from mobile CT head scanning was relatively low.However in order to avoid the damage to the operators and other medical workers from long-term low dose exposure,it should keep 2 m away from mobile CT,beside or behind,when in operation.
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Objective To investigate the feasibility and clinical value of anteroposterior and lateral scout scan combined with Care Dose 4D and Care kV in chest CT scan.Methods A total of 60 patients of clinical diagnosis with lung tumor were enrolled.Those patients were randomly divided into test group and control group.Control group underwent a scan protocol with lateral scout scan combined with Care Dose 4D and Care kV,while anteroposterior and lateral scout scan combined with Care Dose 4D and Care kV were performed in test group.The signal-to-noise ration (SNR),contrast-to-noise ratio (CNR),and overall image quality of two groups of images and diseased tissues were analyzed and evaluated by two high-grade radiologists using double-blind method.Effective doses (E) were also calculated.Results All the 60 patients had successfully completed the chest CT scans.Test group overall image quality (4.57 ± 0.45) and control group overall image quality (4.73 ± 0.45) had no statistically significant difference (P > 0.05).The control group image SNR,CNR and diseased tissue SNR,CNR compared with test group had no statistical significance difference (P > 0.05).The difference of the volume CT dose index (CTDIvol),dose-length product (DLP) and effective dose (E) of test group and control group was statistically significant (t =8.514,8.464,8.464,P < 0.001).Compared with control group,the effective dose of test group decreased by 33.3%.Conclusions Compared with lateral scout scan,the technology of anteroposterior and lateral scout scan combined with Care Dose 4D and Care kV can decrease radiation dose without reducing the image quality.This technology can therefore be considered as a regular imaging modality for chest CT scan.
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Homocysteine (Hcy) is a well-established risk factor for atherosclerosis and may cause dysregulation of gene expression, but the characteristics and the key links involved in its pathogenic mechanisms are still poorly understood. The aim of this study was to explore (i) the effects of Hcy on DNA methylation in vascular smooth muscle cells (VSMCs) and (ii) the underlying mechanism of Hcy-induced changes in DNA methylation patterns in relation to atherosclerosis. We examined the levels of gDNA methylation, namely, the Alu and line-1 element sequences, which can serve as a surrogate marker for gDNA methylation, and also investigated the effects of Hcy on the intracellular S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations as well as the expressions of SAH hydrolase (SAHH), DNA methyltransferase3a (DNMT3a), DNMT3b, and methyl-CpG-binding domain 2 (MBD2). We found that clinically relevant levels of Hcy (0-500 microM) induced elevation of SAH, declination of SAM and SAM/SAH ratio, and reduction in expression of SAHH and MBD2, but increased the activity of DNMT3a and DNMT3b compared to the control group (p < 0.05). We found also that the genome-wide hypomethylation is a common feature of gDNA in the VSMCs cultured with Hcy. In conclusion, these results suggest that Hcy-induced DNA methylation may be an important potential pathogenic mechanism in the development of atherosclerosis, and may become a therapeutic target for preventing Hcy-induced atherosclerosis.