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Arteriovenous fistula (AVF) failure often involves venous neointimal hyperplasia (VNH) driven by elevated hypoxia-inducible factor-1 alpha (HIF-1α) in the venous wall. Omentin, known for its anti-inflammatory and anti-hyperplasia properties, has an uncertain role in early AVF failure. This study investigates omentin's impact on VNH using a chronic renal failure (CRF) rabbit model. The CRF rabbit model of AVF received omentin-expressing adenoviral vector or control ß-gal vector to assess omentin's effects on VNH. Human vascular smooth muscle cells (HVSMCs), stimulated with tumor necrosis factor-α (TNF-α), were exposed to recombinant human omentin (Rh-OMT) to study its influence on cell proliferation and migration. The AMP-activated protein kinase (AMPK) inhibitor compound C and the mammalian target of rapamycin (mTOR) activator MHY1485 were employed to explore omentin's mechanisms in VNH reduction through HIF-1α inhibition. Omentin treatment reduced VNH in CRF rabbits, concomitant with HIF-1α down-regulation and the suppression of downstream factors, including vascular endothelial growth factor and matrix metalloproteinases. Rh-OMT inhibited TNF-α-induced HVSMC proliferation and migration by modulating both cell cycle and cell adhesion proteins. Additionally, omentin reduced HIF-1α expression through the AMPK/mTOR pathway activation. Notably, the blockade of AMPK/mTOR signaling reversed omentin-mediated inhibition of VNH, cell proliferation, and migration, both in vivo and in vitro. In conclusion, omentin mitigates VNH post-AVF creation by restraining HIF-1α via AMPK/mTOR signaling. Strategies boosting circulating omentin levels may offer promise in averting AVF failure.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Derivación Arteriovenosa Quirúrgica , Movimiento Celular , Proliferación Celular , Citocinas , Modelos Animales de Enfermedad , Proteínas Ligadas a GPI , Hiperplasia , Subunidad alfa del Factor 1 Inducible por Hipoxia , Lectinas , Músculo Liso Vascular , Miocitos del Músculo Liso , Neointima , Transducción de Señal , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Citocinas/metabolismo , Conejos , Humanos , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/farmacología , Proteínas Ligadas a GPI/genética , Proliferación Celular/efectos de los fármacos , Miocitos del Músculo Liso/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Lectinas/farmacología , Lectinas/metabolismo , Movimiento Celular/efectos de los fármacos , Músculo Liso Vascular/patología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Células Cultivadas , Derivación Arteriovenosa Quirúrgica/efectos adversos , Masculino , Fallo Renal Crónico/patología , Serina-Treonina Quinasas TOR/metabolismo , Oclusión de Injerto Vascular/patología , Oclusión de Injerto Vascular/prevención & control , Oclusión de Injerto Vascular/metabolismo , Oclusión de Injerto Vascular/fisiopatología , Venas Yugulares/patología , Venas Yugulares/metabolismo , Venas Yugulares/trasplanteRESUMEN
Objective To investigate the predictive value of serum thrombospondin-1(THBS-1),D-dimer(D-D)and tissue inhibitor of metalloproteinase-1(TIMP-1)levels in late pregnancy for postpartum hemorrhage(PPH)in re-pregnant women with scarred uterus.Methods Totally 108 re-pregnant women with scarred uterus admitted to the First Affiliated Hospital of Xinxiang Medical University from June 2020 to August 2022 were selected and divided into the PPH group(n=21)and the non-PPH group(n=87)according to whether PPH occurred after delivery.On the day of admission,5 mL elbow venous blood was collected from re-pregnant women in the two groups,and the levels of serum THBS-1,D-D and TIMP-1 of pregnant women in the two groups were detected by enzyme-linked immunosorbent assay.The serum THBS-1,D-D TIMP-1 levels and clinical data of pregnant women between the two groups were compared.The influencing factors on the occurrence of PPH in re-pregnant women with scarred uterus were analyzed by multivariate logistic regression,and the predictive value of serum THBS-1,D-D and TIMP-1 levels on the occurrence of PPH in re-pregnant women with scarred uterus was evaluated by receiver operating characteristic curve.Results The percentage of patients with ≥ 2 induced abortions,placental abruption,uterine incision laceration,uterine inertia or scar thickness<0.3 cm,as well as serum THBS-1 and D-D levels in late pregnancy in the PPH group were significantly higher than those in the non-PPH group,and serum TIMP-1 level in late pregnancy were significantly lower than that in the non-PPH group(P<0.05).The uterine inertia,as well as high D-D and THBS-1 levels,were independent risk factors for PPH in re-pregnant women with scarred uterus(P<0.05),and low TIMP-1 level was a protective factor(P<0.05).The area under the curve of combined serum THBS-1,D-D and TIMP-1 levels to predict PPH in re-pregnant women with scarred uterus was greater than that predicted by the three factors alone(P<0.05).Conclusion Serum THBS-1,D-D and TIMP-1 levels in late pregnancy can be used as reference indicators for predicting the occurrence of PPH in re-pregnant women with scarred uterus,and the combination of the three indexes is more effective in predicting the occurrence of PPH.
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Recent studies have demonstrated that SARS-CoV-2 cell entry depends on both ACE2 and TMPRSS2 genes (DOI: 10.1016/j.cell.2020.02.052), but our current work only focus on ACE2, which is insufficient to support the conclusion of this paper. So the authors have withdrawn their manuscript whilst they perform additional experiments and analysis to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project.
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By analyzing the training of resident doctors in the University of Maryland Shock Trauma, this paper compared the similarities and differences of standardized resident training between China and the United States in policy, training base, selection of teaching teachers, selection of training objects, assessment methods and financial subsidies to the students. It can be concluded that standardized resident training of orthopedics in the United States is more purposeful and systematic and pays more attention to the connection between knowledge and clinical practice, skills and operation, and the cultivation of the ability to deal with patients independently. The training of orthopedics residents in the United States began earlier and had more experience than China, which can be an example for the standardized training of orthopedics residents in China.
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BACKGROUND:Foreign injectable sulphate calcium has good biocompatibility, injectability and in situimmobilization, moulding based on adaptation to the shape of bone defects, but the price is expensive. OBJECTIVE:To explore the optimal fabricating parameters of bone repair materials with α-calciumsulfate hemihydrates as the main component, and to study the performance and characterization METHODS:α-Calciumsulfate hemihydrates powder was mixed with sodium hyaluronate at liquid-solid-ratios of 0.2, 0.25, 0.3, 0.35, 0.4 mL/g using vapor-heat method to prepare injectable bone materials. Performance, setting time and compressive strength of the injectable bone was detected. The best liquid-solid-ratio was 0.3 mL/g.α-Calcium sulfate hemihydrates powder was mixed with calcium sulfate dihydrate powder (1%, 2%, 3% mass fractionas) to fabricate injectable bone materials. Performance, setting time and compressive strength of the injectable bone was also detected; meanwhile, the biosafety of the injectable bone was determined. Theinjectable bone material that was made at the liquid-solid-ratio of 0.3 mL/g and by 2% calcium sulfate dihydrate was implanted into Ba-ma swine models of thoracic bone defects. At the time points of 8, 16 and 24 weeks after implantation, histological observation was done. RESULTS AND CONCLUSION: The injectable bone material was made at the liquid-solid-ratio of 0.3 mL/g and by 2% calcium sulfate dihydrate. The initial and final setting time was 4.0-5.0 minutes and 8.0-9.0 minutes, respectively. The compressive strength of the injectable bone reached (8.93±0.23) MPa. These findings indicate that the injectable boen material has good performance, initial setting time and compressive strength meeting the requirements of clinical application and good biosafety. Animal experiments show that the injectable bone can provide space for new bone in creeping substitution way by auto-degradation, with osteogenic activity.
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<p><b>OBJECTIVE</b>To compare the consistency of root canal configuration types of mandibular first premolar by using micro-CT and radio visio graphy (RVG).</p><p><b>METHODS</b>One hundred extracted mandibular first premolars with complete dental root and apex which received no endodontic treatment were randomly selected. Each tooth was radiographed with RVG through a buccolingual and mesiodistal direction, and then scanned with micro-CT and reconstructed. The classifications of the root canal types according to Vertucci's type with the two methods were compared.</p><p><b>RESULTS</b>The canal patterns were classified as type I (67%), type III (3%), type V (18%), type VII (2%), additional type (10%) with micro-CT and canal patterns as type I (71%), type III (2%), type V (23%), type VII (1%), additional type (3%) with RVG. 63% of teeth showed one canal in both micro-CT and RVG. Only 25% of teeth were diagnosed as complex canal by the same canal type in both micro-CT and RVG. The Kappa value between micro-CT and RVG was 0.541 which suggested that the two kinds of methods had intermediate consistency. 82.8% of the premolars with root groove had two or more than two canals.</p><p><b>CONCLUSION</b>Although RVG can basically reflect the root canal system type of the mandibular first premolars in vitro, it offers poor accuracy images to complex root canals. Micro-CT three-dimensional images could clearly and precisely display the root canal system morphology of the mandibular first pre-molars in vitro.</p>