Search

Abstract Background MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. Results We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4 × 108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels, a typical characteristics of saturated miRNA-sequencing. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Gene Ontology analysis of the predicted and validated targets of the 24 differentially expressed miRNAs indicated enrichment of functional pathways involved in cell metabolism, cell cycle, cell signaling, and cell differentiation. A cross sectional expression analysis of the differentially expressed miRNAs in B-cells from Ashkenazi Jewish individuals between the 50th and 100th years of age indicated that expression levels of miR-363* declined significantly with age. Centenarians, however, maintained the youthful expression level. This result suggests that miR-363* may be a candidate longevity-associated miRNA. Conclusion Our comprehensive miRNA data provide a resource for further studies to identify genetic pathways associated with aging and longevity in humans.

The formation of nerve bundles, which is partially regulated by neural cell adhesion molecule 1 (NCAM1), is important for neural network organization during peripheral nerve regeneration. However, little is known about how the extracellular matrix (ECM) microenvironment affects this process. Here, we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrix-gel, Matrigel, laminin 521, collagen I, and collagen IV, and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment. We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon. A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation. Collagen VI interacted with NCAM1 by directly binding to the FNIII domain, thereby increasing the stability of NCAM1 at the axolemma. Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/mL Matrigel and 20 μg/mL collagen VI. These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation. This study was approved by the Animal Ethics Committee of Guangzhou Medical University (approval No. GY2019048) on April 30, 2019.

PurposeTo investigate the effect of sub-satisfactory stent recanalization on hemodynamic stresses for severe stenoses of the middle cerebral artery (MCA) M 1 segment.Materials and methodsPatients with severe stenoses of the MCA M1 segment treated with endovascular stent angioplasty were retrospectively enrolled. Three-dimensional digital subtraction angiography before and after stenting was performed; the computational fluid dynamics (CFD) analysis of hemodynamic stresses at the stenosis and normal segments proximal and distal to the stenoses was analyzed.ResultsFifty-one patients with severe stenosis at the MCA M1 segment were enrolled, with the stenosis length ranging from 5.1 to 12.8 mm (mean 9 ± 3.3 mm). Stent angioplasty was successful in all (100%) the patients. The angiography immediately after stenting demonstrated a significant (P < 0.05) decrease in MCA stenosis after comparison with before stenting (31.4 ±12.5% vs. 87.5 ± 9.6%), with residual stenosis of 15–30% (mean 22.4 ± 3.5%). Before stenting, the total pressure was significantly higher (P < 0.0001), while the WSS, velocity, and vorticity were all significantly decreased (P < 0.0001) at the normal arterial segment proximal to the stenosis, and the total pressure, WSS, velocity, and vorticity were all significantly decreased (P < 0.0001) at the normal arterial segment distal to the stenosis compared with those at the stenosis. After sub-satisfactory stenting recanalization, all the hemodynamic stresses proximal or distal to the stenosis and at the perforator root were improved compared with those before stenting and were similar to those after virtual stenosis removal.ConclusionSub-satisfactory recanalization of severe MCA stenoses can significantly improve the hemodynamic status for cerebral perfusion at the stenoses.

PurposeTo investigate the effect and safety of flow diverters in the treatment of unruptured dissecting intracranial aneurysms of the vertebral artery in comparison with stent-assisted coiling or stenting alone.Materials and methodsPatients with unruptured dissecting intracranial aneurysms of the vertebral artery treated with the flow diverter, stent-assisted coiling, or stenting alone were retrospectively enrolled. The clinical data were analyzed and compared.ResultsTwenty-five patients were enrolled in the flow diversion group and 42 patients in the stenting group. Twenty-six flow diverters were deployed in the flow diversion group. Immediate angiography revealed contrast agent retention within the aneurysm cavity in all patients. In the stenting group, 48 stents were deployed, and immediate angiographic outcome showed O'Kelly-Marotta (OKM) grade D in 18 (42.9%) aneurysms, grade C in 16 (38.1%), and grade B in 8 (19.0%). Periprocedural ischemic complications of thrombosis occurred in two (4.8%) patients and were treated with thrombolysis. In the flow diversion group, 19 (76%) patients underwent angiographic follow-up 3–46 (median 24) months after the procedure, with the OKM grade D in 11 (57.9%) patients, C in two (10.5%), and B in six (31.6%). The aneurysm recurrence rate was zero, and all diverters remained patent. Asymptomatic instent stenosis occurred in two (10.5%) patients. In seven of the ten patients with mild or moderate parent artery stenosis before the procedure who experienced angiographic follow-up, the stenosis was improved in five (71.4%) patients. In the stenting group, angiographic follow-up was carried out in 33 (78.6%) patients 6–58 months (median 34) after the procedure, with OKM grade D in 22 (66.7%) patients, grade C in five (15.2%), grade B in three (9.1%), and aneurysm recurrence (grade B, with increased contrast agent into the aneurysm cavity) in three (9.1%). Five (16.7%) patients experienced asymptomatic instent stenosis, and six of the 12 patients (50%) with parent artery stenosis were improved.ConclusionFlow diverters with or without selective adjunctive coiling for the treatment of unruptured dissecting intracranial aneurysms of the vertebral artery may be safe and effective with good occlusion effects not inferior to those of stent-assisted coiling and stenting alone even though the long-term effect still warrants confirmation.

Abstract This study investigated factors affecting the safety and in-stent restenosis after intracranial stent angioplasty using the Enterprise stent for symptomatic intracranial atherosclerotic stenosis. Between January 2017 and March 2019, patients with intracranial atherosclerotic stenosis treated with Enterprise stent angioplasty were enrolled, including 400 patients in the modeling group and 89 patients in the validation group. The clinical factors affecting in-stent restenosis after Enterprise stent angioplasty in the modeling group were analyzed, and a logistic regression model of these factors was established and validated in the validation group. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were analyzed. In the modeling group with 400 patients, there were 410 lesions, including 360 stenotic lesions and 50 occluded lesions, with 176 (42.9%) lesions in the anterior circulation and 234 (57.1%) in the posterior circulation. Successful stenting was performed in 398 patients (99.5%). Stenosis was significantly (P

ObjectiveThe purpose of this work was to summarize the real-world safety and efficacy of Pipeline Embolization Device (PED) therapy for small and medium-sized intracranial aneurysms in China.MethodsPatients from the PED in China post-market multi-center registry study (PLUS) with aneurysms smaller than 12 mm were selected. Radiographic outcomes were assessed using digital subtraction angiography. Clinical outcomes included functional outcomes (modified Rankin Scale, MRS) in the early postoperative period ( ≤ 30 days) and early postoperative complications associated with PED therapy.ResultsA total of 652 patients with a combined 754 aneurysms were included in this study (mean age of 53.9 ± 10.3 years, 68.7% women). Mean aneurysm diameter was 6.78 ± 2.67 mm. Of the 687 stents deployed, 99.7% (685/689) were successfully deployed. In this study, 64.7% (488/754) of aneurysms were treated with only the PED, whereas 35.3% (266/754) were subjected to PED-assisted therapy. Radiographic outcome at the last follow-up (median time: seven months) was available for 64.3% (485/754) of the aneurysms. 82.5% (400/485) of aneurysms demonstrated complete occlusion (Raymond Roy Grade I). 81.4% (395/485) of aneurysms were found to meet the study's primary effectiveness outcome. At the early postoperative period, the mRS score was determined to be 0–2 vs. 3-6 in 98.2% (640/652) vs. 1.8% (12/652) of the cases, respectively. The combined major morbidity and mortality rate was 3.2% (21/652).ConclusionIn the largest study of PED therapy for small and medium-sized intracranial aneurysms to date, pipeline-assisted coil embolization was chosen more often than multiple stent implantation for aneurysm treatment, demonstrating good results, high surgical success rates, high occlusion rates, and low morbidity and mortality.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT03831672.

Abstract Background Phelan-McDermid syndrome (PMS), also known as 22q13.3 deletion syndrome, is a rare neurodevelopmental syndrome resulting from a deletion of the distal long arm of chromosome 22. Case presentation We report a case of a 21 months old Chinese girl presenting with global developmental delay, regression of language skills, unable to understand a few words or walk independently, insomnia, and autism-like behaviors. Copy number variation (CNV) analysis showed a heterozygous loss of SHANK3 gene in the 22q13 region, consistent with a diagnosis of PMS. After treatment with recombinant human growth hormone (rhGH), this patient had an improvement in motor skills and social behaviors. No side effects from rhGH therapy were reported. Conclusions This is the first report of using rhGH to treat a Chinese girl diagnosed with PMS. We speculate rhGH could be a reasonable alternative choice for PMS treatment with similar clinical outcomes in comparison to insulin-like growth factor-1(IGF-1). However, further clinical trials are needed to confirm this hypothesis.

In this study, the type I caramel reactions of the glucose-water system were carried out. The glucose caramel products (GCPs) at different reaction stages were collected and the reaction rate, UV absorption, flavor compound, and the antioxidant and antibacterial activities were determined. The result showed that the glucose reaction rate of the GCP yielded at 180°C and 4 min arrived at the stable range of around 80.0%. For UV absorptions of GCPs at 305 nm increased approximately in the exponential order. Moreover, the GCP yielded at 180°C and 4 min was revealed to have the highest concentration of main flavor compounds and potent antioxidant and antibacterial activities.

Cerebral arteries are usually tortuous, and in the treatment of cerebrovascular diseases with stenting, a stent deployed may be collapsed at one end, leading to reduced blood flow and subsequent stent occlusion. Immediate rescuing measures should be implemented to prevent severe ischemic events. In this case report, we present a case with V4 segment occlusion of the right vertebral artery treated with endovascular stent angioplasty. An Enterprise stent deployed at the occlusion segment was collapsed at the proximal end after withdrawal of the delivery system. Immediate rescuing measures were taken by navigating a micro-guidewire through the lateral stent mesh at the proximal end into the stent lumen followed by advancing a second micro-guidewire right through the reopened proximal stent end into the stent lumen for deployment of a supporting balloon-expandable Apollo stent to prevent stent collapse. Follow-up digital subtraction angiography 6 months later demonstrated patent stents and unobstructed blood flow.