ONE-seq: epitranscriptome and gene-specific profiling of NAD-capped RNA.

The hub metabolite, nicotinamide adenine dinucleotide (NAD), can be used as an initiating nucleotide in RNA synthesis to result in NAD-capped RNAs (NAD-RNA). Since NAD has been heightened as one of the most essential modulators in aging and various age-related diseases, its attachment to RNA might indicate a yet-to-be discovered mechanism that impacts adult life-course. However, the unknown identity of NAD-linked RNAs in adult and aging tissues has hindered functional studies. Here, we introduce ONE-seq method to identify the RNA transcripts that contain NAD cap. ONE-seq has been optimized to use only one-step chemo-enzymatic biotinylation, followed by streptavidin capture and the nudix phosphohydrolase NudC-catalyzed elution, to specifically recover NAD-capped RNAs for epitranscriptome and gene-specific analyses. Using ONE-seq, we discover more than a thousand of previously unknown NAD-RNAs in the mouse liver and reveal epitranscriptome-wide dynamics of NAD-RNAs with age. ONE-seq empowers the identification of NAD-capped RNAs that are responsive to distinct physiological states, facilitating functional investigation into this modification.

MiR-127-3p enhances macrophagic proliferation via disturbing fatty acid profiles and oxidative phosphorylation in atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic pathology, leading to acute coronary heart disease or stroke. MiR-127 has been found significantly upregulated in advanced atherosclerosis. But its function in atherosclerosis remains unexplored. We explored the role of miR-127-3p in regulating atherosclerosis development and its downstream mechanisms. METHODS: The expression profile of miR-127 in carotid atherosclerotic plaques of 23 patients with severe carotid stenosis was detected by RT-qPCR and in situ hybridization. Primary bone marrow-derived macrophages (BMDM) stimulated with oxidized low-density lipoprotein were used as an in vitro model. CCK-8, EdU, RT-qPCR, and flow cytometry were used to detect the proliferative capacity and polarization of BMDM, which were infected by lentivirus-carrying plasmid to upregulate or downregulate miR-127-3p expression, respectively. RNA sequencing combined with bioinformatic analysis and targeted fatty acid metabolomics approach were used to detect the transcriptome and lipid metabolites. The association between miR-127-3p and its target was verified by dual-luciferase activity reporting and Western blotting. Oxygen consumption rate of BMDM were detected using seahorse analysis. High-cholesterol-diet-fed low density lipoprotein deficient (LDLR-/-) mice, with-or-without carotid tandem-stenosis surgery, were treated with miR-127-3p agomir or antagomir to examine its effect on plaque development and stability. RESULTS: miR-127-3p, not -5p, is elevated in human advanced carotid atheroma and its expression is positively associated with macrophage accummulation in plaques. In vitro, miR-127-3p-overexpressed macrophage exhibites increased proliferation capacity and facilitates M1 polariztion whereas the contrary trend is present in miR-127-3p-inhibited macrophage. Stearoyl-CoA desaturase-1 (SCD1) is one potential target of miR-127-3p. miR-127-3p mimics decreases the activity of 3' untranslated regions of SCD-1. Furthermore, miR-127-3p downregulates SCD1 expression, and reversing the expression of SCD1 attenuates the increased proliferation induced by miR-127-3p overexpression in macrophage. miR-127-3p overexpression could also lead to decreased content of unsaturated fatty acids (UFAs), increased content of acetyl CoA and increased level of oxidative phosphorylation. In vivo, miR-127-3p agomir significantly increases atherosclerosis progression, macrophage proliferation and decreases SCD1 expression and the content of UFAs in aortic plaques of LDLR-/- mice. Conversely, miR-127-3p antagomir attenuated atherosclerosis, macrophage proliferation in LDLR-/- mice, and enhanced carotid plaque stability in mice with vulnerable plaque induced. CONCLUSION: MiR-127-3p enhances proliferation in macrophages through downregulating SCD-1 expression and decreasing the content of unsaturated fatty acid, thereby promoting atherosclerosis development and decreasing plaque stability. miR-127-3p/SCD1/UFAs might provide potential therapeutic target for anti-inflammation and atherosclerosis.

External validation of a convolutional neural network algorithm for opportunistically detecting vertebral fractures in routine CT scans.

The Convolutional Neural Network algorithm achieved a sensitivity of 94% and specificity of 93% in identifying scans with vertebral fractures (VFs). The external validation results suggest that the algorithm provides an opportunity to aid radiologists with the early identification of VFs in routine CT scans of abdomen and chest. PURPOSE: To evaluate the performance of a previously trained Convolutional Neural Network (CNN) model to automatically detect vertebral fractures (VFs) in CT scans in an external validation cohort. METHODS: Two Chinese studies and clinical data were used to retrospectively select CT scans of the chest, abdomen and thoracolumbar spine in men and women aged ≥50 years. The CT scans were assessed using the semiquantitative (SQ) Genant classification for prevalent VFs in a process blinded to clinical information. The performance of the CNN model was evaluated against reference standard readings by the area under the receiver operating characteristics curve (AUROC), accuracy, Cohen's kappa, sensitivity, and specificity. RESULTS: A total of 4,810 subjects were included, with a median age of 62 years (IQR 56-67), of which 2,654 (55.2%) were females. The scans were acquired between January 2013 and January 2019 on 16 different CT scanners from three different manufacturers. 2,773 (57.7%) were abdominal CTs. A total of 628 scans (13.1%) had ≥1 VF (grade 2-3), representing 899 fractured vertebrae out of a total of 48,584 (1.9%) visualized vertebral bodies. The CNN's performance in identifying scans with ≥1 moderate or severe fractures achieved an AUROC of 0.94 (95% CI: 0.93-0.95), accuracy of 93% (95% CI: 93%-94%), kappa of 0.75 (95% CI: 0.72-0.77), a sensitivity of 94% (95% CI: 92-96%) and a specificity of 93% (95% CI: 93-94%). CONCLUSION: The algorithm demonstrated excellent performance in the identification of vertebral fractures in a cohort of chest and abdominal CT scans of Chinese patients ≥50 years.

METTL3-mediated m6A modification of NORAD inhibits the ferroptosis of vascular smooth muscle cells to attenuate the aortic dissection progression in an YTHDF2-dependent manner.

Ferroptosis of vascular smooth muscle cells (VSMCs) is related to the incidence of aortic dissection (AD). Long non-coding RNA (lncRNA) NORAD plays a crucial role in the progression of various diseases. The present study aimed to investigate the effects of NORAD on the ferroptosis of VSMCs and the molecular mechanisms. The expression of NORAD, HUR, and GPX4 was detected using quantitative real-time PCR (qPCR) or western blot. Ferroptosis was evaluated by detecting lactate dehydrogenase (LDH) activity, lipid reactive oxygen species (ROS), malonaldehyde (MDA) content, L-Glutathione (GSH) level, Fe2+ content, and ferroptosis-related protein levels. The molecular mechanism was assessed using RNA pull-down, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. The histology of aortic tissues was assessed using H&E, elastic Verhoeff-Van Gieson (EVG), and Masson staining assays. The data indicated that NORAD was downregulated in patients with AD and AngII-treated VSMCs. Overexpression of NORAD promoted VSMC growth and inhibited the ferroptosis induced by AngII. Mechanistically, NORAD interacted with HUR, which promoted GPX4 mRNA stability and elevated GPX4 levels. Knockdown of GPX4 abrogated the effects of NORAD on cell growth and ferroptosis of AngII-treated VSMCs. Moreover, METTL3 promoted m6A methylation of NORAD in an YTHDF2-dependent manner. In addition, NORAD attenuated AAD symptoms, incidence, histopathology, inflammation, and ferroptosis in AAD mice. In conclusion, METTL3-mediated NORAD inhibited ferroptosis of VSMCs via the HUR/GPX4 axis and decelerated AAD progression, suggesting that NORAD may be an AD therapeutic target.

Low muscle density in children with osteogenesis imperfecta using opportunistic low-dose chest CT: a case-control study.

BACKGROUND: The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children. METHODS: This single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests. RESULTS: 20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p < 0.01; 37.3 HU vs. 45.9 HU, p < 0.01). However, children with OI had lower T4 muscle size, T4 muscle density, T10 muscle size and T10 muscle density than controls measured by the Gaussian mixture model (110.9 vs. 127.2 cm2, p = 0.03; 44.6 HU vs. 51.3 HU, p < 0.01; 72.6 vs. 88.0 cm2, p = 0.01; 41.6 HU vs. 50.3 HU, p < 0.01, respectively). CONCLUSIONS: Children with OI had lower trunk muscle density indicating that OI might also impair muscle quality. Moreover, the fixed thresholds may not be suitable for segmentation of muscle in children.

Inter-rater variability and repeatability in the assessment of the Tanner-Whitehouse classification of hand radiographs for the estimation of bone age.

OBJECTIVE: To determine which bones and which grades had the highest inter-rater variability when employing the Tanner-Whitehouse (T-W) method. MATERIALS AND METHODS: Twenty-four radiologists were recruited and trained in the T-W classification of skeletal development. The consistency and skill of the radiologists in determining bone development status were assessed using 20 pediatric hand radiographs of children aged 1 to 18 years old. Four radiologists had a poor concordance rate and were excluded. The remaining 20 radiologists undertook a repeat reading of the radiographs, and their results were analyzed by comparing them with the mean assessment of two senior experts as the reference standard. Concordance rate, scoring, and Kendall's W were calculated to evaluate accuracy and consistency. RESULTS: Both the radius, ulna, and short finger (RUS) system (Kendall's W = 0.833) and the carpal (C) system (Kendall's W = 0.944) had excellent consistency, with the RUS system outperforming the C system in terms of scores. The repeatability analysis showed that the second rating test, performed after 2 months of further bone age assessment (BAA) practice, was more consistent and accurate than the first. The capitate had the lowest average concordance rate and scoring, as well as the lowest overall concordance rate for its D classification. Moreover, the G classifications of the seven carpal bones all had a concordance rate less than 0.6. The bones with lower Kendall's W were likewise those with lower scores and concordance rates. CONCLUSION: The D grade of the capitate showed the highest variation, and the use of the Tanner-Whitehouse 3rd edition (T-W3) to determine bone age (BA) was frequently inconsistent. A more comprehensive description with a focus on inaccuracy bones or ratings and a modification to the T-W3 approach would significantly advance BAA.

Greater bone marrow fat and myosteatosis are associated with lower vBMD but not asymptomatic vertebral fracture.

OBJECTIVES: Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT). METHODS: Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women). RESULTS: Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (ß, -24.00; 95% CI, -28.54 to -19.46 mg/cm3). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years. CONCLUSIONS: In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures. KEY POINTS: • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures.

The association of lumbar disc degeneration with lumbar vertebral trabecular volumetric bone mineral density in an urban population of young and middle-aged community-dwelling Chinese adults: a cross-sectional study.

INTRODUCTION: Lumbar intervertebral disc degeneration (LDD) and osteoporosis (OP) are age-related conditions that induce low back pain and have an impact on quality of life. The relationship between LDD and changes in bone mineral density (BMD) is, however, contentious and ever-changing. The purpose of this study is to investigate the relationship between lumbar vertebral volumetric BMD (vBMD) and LDD in an urban population of young and middle-aged community-dwelling Chinese adults. MATERIALS AND METHODS: 719 participants were recruited from among the subjects enrolled in a 10-year longitudinal study of degeneration of the spine and knee being conducted at the Beijing Jishuitan Hospital. The severity of LDD was graded using the five-grade Pfirrmann classification, and lumbar vertebral vBMD was measured using quantitative computed tomography (QCT). The relationship between the grade of intervertebral disc degeneration and lumbar vertebral vBMD was analyzed, and multiple linear regression was performed to adjust for covariates. RESULTS: The mean lumbar vBMD decreased as the grade of LDD increased (171.5 g/cm3, 147.8 g/cm3, and 124.3 g/cm3, respectively; P < 0.001). After adjusting for age, a higher LDD stage was associated with a lower mean L2-L4 vBMD, although a statistically significant correlation was observed only in men (standardized coefficient ß = - 0.656, P = 0.004). In men, there was a negative correlation between single-vertebra vBMD and degeneration of adjacent intervertebral discs, particularly those involving the L3 vertebra (L2-3 disc: ß = - 0.333, P < 0.001, L3-4 disc: ß = - 0.398, P < 0.001), as well as the mean grade of the L2-4 discs (ß = - 0.448, P < 0.001). However, the L5-S1 disc had a smaller correlation with age than others, and no statistically significant associations with lumbar vBMD were observed in either men (ß = - 0.024, P = 0.729) or women (ß = - 0.057, P = 0.396). CONCLUSION: Our study found that the degree of LDD was negatively associated with lumbar trabecular vBMD, although (excepting the L5-S1 disc), the relationship was statistically significant only in men.

The lumbar spinal endplate lesions grades and association with lumbar disc disorders, and lumbar bone mineral density in a middle-young general Chinese population.

BACKGROUND: Lumbar vertebral endplates lesions (LEPLs), one of the etiologies of low back pain (LBP), are one of the most prevalent causes of health-care costs. Despite progressively becoming the focus in recent years, almost all studies have concentrated on symptomatic patients rather than general populations. As a result, our study was designed to determine the prevalence and distribution patterns of LEPLs in a middle-young general population, as well as their associations with lumbar disc herniation (LDH), lumbar disc degeneration (LDD), and lumbar vertebral volumetric bone mineral density (vBMD). METHODS: Seven hundred fifty-four participants aged 20-60 years were recruited from the subjects enrolled in a 10-year longitudinal study of degeneration of the spine and knee being conducted at the Beijing Jishuitan Hospital and 4 of them were excluded due to the missing of MRIs. In this observational study, a lumbar quantitative computed tomography (QCT) and MRI scan were performed among participants within 48 h. T2-weighted sagittal lumbar MRI images for all included subjects were identified for LEPLs by two independent observers based on morphological and local characteristics. Lumbar vertebral vBMD was measured with QCT. The age, BMI, waistline, hipline, lumbar vBMD, LDD, and LDH were measured to investigate their associations with LEPLs. RESULTS: The prevalence of LEPLs was higher among the male subjects. 80% of endplates were recognition as no lesions with a substantial disparity between female (75.6%) and male subjects (83.4%) (p < 0.001). The most common lesions were "wavy/irregular" and "notched", and "fracture" is most involved in L3-4 inferior endplate both in two genders. LEPLs were found to be associated with LDH (≥ 2 levels: OR = 6.859, P < 0.001; 1 level: OR = 2.328, P = 0.002 in men. OR = 5.004, P < 0.001; OR = 1.805, P = 0.014 in women) reference for non-LDH, and hipline in men (OR = 1.123, P < 0.001). CONCLUSIONS: LEPLs are the common findings on lumbar MRIs in general population, particularly in men. The presence of these lesions and advance from slightly to severely could be mainly attributed to LDH and men's higher hipline.

Long-term outcomes of thoracic endovascular repair with quick fenestrater assisted in situ fenestration for type B aortic dissection.

OBJECTIVES: To report the long-term outcomes of patients with type B aortic dissection (TBAD) treated with thoracic endovascular aortic repair (TEVAR) and quick fenestrated (QF)-assisted in situ fenestration (ISF). METHODS: Between October 2017 and December 2018, 15 patients with TBAD requiring revascularization of the supra-aortic trunks underwent TEVAR with QF-assisted ISF at our institution. RESULTS: Thirteen of the 15 patients were male, and the mean age was 52.87 ± 11.26. The technical success rate was 100%. Thirty-day mortality rate was 0. The median follow-up period was 41 months (range, 35-49). During follow-up, one non-aortic-related death was recorded, no fenestration lost its alignment, and no stroke or stent graft migration was observed. Two patients underwent another successful endovascular repair. One case of type Ib endoleak occurred 19 months postoperatively. This was caused by aortic progression distal to the stent graft. Another stent graft with a larger diameter was implanted in the descending aorta. One case of type Ic endoleak was observed 35 months postoperatively. The patient was diagnosed during the annual follow-up without any symptoms. Another bridging stent graft was implanted into the left subclavian artery distal to the already existing one, and the type Ic endoleak was successfully treated. CONCLUSIONS: TEVAR with QF-assisted ISF may be an effective treatment for ISF in type B aortic dissection.

Mitochondrial aldehyde dehydrogenase (ALDH2) rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer's disease via inhibition of ACSL4-dependent ferroptosis.

Alzheimer's disease (AD) is associated with high incidence of cardiovascular events but the mechanism remains elusive. Our previous study reveals a tight correlation between cardiac dysfunction and low mitochondrial aldehyde dehydrogenase (ALDH2) activity in elderly AD patients. In the present study we investigated the effect of ALDH2 overexpression on cardiac function in APP/PS1 mouse model of AD. Global ALDH2 transgenic mice were crossed with APP/PS1 mutant mice to generate the ALDH2-APP/PS1 mutant mice. Cognitive function, cardiac contractile, and morphological properties were assessed. We showed that APP/PS1 mice displayed significant cognitive deficit in Morris water maze test, myocardial ultrastructural, geometric (cardiac atrophy, interstitial fibrosis) and functional (reduced fractional shortening and cardiomyocyte contraction) anomalies along with oxidative stress, apoptosis, and inflammation in myocardium. ALDH2 transgene significantly attenuated or mitigated these anomalies. We also noted the markedly elevated levels of lipid peroxidation, the essential lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4), the transcriptional regulator for ACLS4 special protein 1 (SP1) and ferroptosis, evidenced by elevated NCOA4, decreased GPx4, and SLC7A11 in myocardium of APP/PS1 mutant mice; these effects were nullified by ALDH2 transgene. In cardiomyocytes isolated from WT mice and in H9C2 myoblasts in vitro, application of Aß (20 µM) decreased cell survival, compromised cardiomyocyte contractile function, and induced lipid peroxidation; ALDH2 transgene or activator Alda-1 rescued Aß-induced deteriorating effects. ALDH2-induced protection against Aß-induced lipid peroxidation was mimicked by the SP1 inhibitor tolfenamic acid (TA) or the ACSL4 inhibitor triacsin C (TC), and mitigated by the lipid peroxidation inducer 5-hydroxyeicosatetraenoic acid (5-HETE) or the ferroptosis inducer erastin. These results demonstrate an essential role for ALDH2 in AD-induced cardiac anomalies through regulation of lipid peroxidation and ferroptosis.

In Vivo Assessment of Age- and Loading Configuration-Related Changes in Multiscale Mechanical Behavior of the Human Proximal Femur Using MRI-Based Finite Element Analysis.

BACKGROUND: MRI-based finite element analysis (MRI-FEA) is the only method able to assess microstructural and whole-bone mechanical properties of the hip in vivo. PURPOSE: To examine whether MRI-FEA is capable of discriminating age-related changes in whole-bone mechanical performance and micromechanical behavior of the proximal femur, particularly considering the most common hip fracture-related sideways fall loading. STUDY TYPE: Retrospective. SUBJECTS: A total of nine younger (27 ± 3.2 years) and nine elderly (61 ± 3.9 years) healthy volunteers. FIELD STRENGTH/SEQUENCE: 3T; 3D fast field echo sequence. ASSESSMENT: The left proximal femurs were scanned and FE models created. FEA was performed to simulate sideways fall and stance loading for each femoral model. Apparent stiffness and high-risk (90th percentile) tensile and compressive strains of the proximal femur as well as the average strains within cubic regions of the femoral neck and greater trochanter were assessed. STATISTICAL TESTS: Paired and unpaired t-tests. RESULTS: Compared to the young group, the femoral stiffness of the elderly decreased by 39% and 40% (both P < 0.05) under the sideways fall and stance conditions, respectively. Accordingly, the high-risk tensile and compressive stains were elevated with aging (40% and 23% for sideways fall, 23% and 11% for stance conditions; all P < 0.05). However, the loading configuration-induced difference was only observed in the elderly group for the high-risk strains (22% for tension and 12% for compression; both P < 0.05). Additionally, compared to the stance condition, the sideways fall increased the average tensile (young: 108%, elderly: 123%; both P < 0.05) and compressive strains (young: 631%, elderly: 617%, both P < 0.05) within the greater trochanter rather than the femoral neck region. DATA CONCLUSION: In vivo MRI-FEA is capable of capturing age-related changes in both apparent-level stiffness and tissue-level micromechanical behavior of the proximal femur. However, the effect of sideways fall loading might be better reflected by tissue-level micromechanics rather than apparent stiffness. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Endovascular and Hybrid Interventions for Extracranial Juxta-Skullbase Carotid Artery Aneurysms: Experience and Long-Term Results.

BACKGROUND: Hybrid and endovascular procedures maybe effective and less invasive alternatives to open surgery for treatment of extracranial carotid artery aneurysm (ECAA), but the optimal management of juxta-skullbase ECAA is controversial. OBJECTIVE: This study evaluated the long-term effects of hybrid and endovascular procedures in treating juxta-skullbase ECAA. METHODS: The records of 9 consecutive patients who underwent hybrid or endovascular interventions for juxta-skullbase ECAA in a single center from April 2014 to May 2020 were retrospectively reviewed. RESULTS: Four patients presented with a pulsating mass, 1 with dysphagia, 1 with pain in the left temporal region, 1 with dizziness and headache, 1 with cerebral infarction, and 1 with dizziness and cerebral infarction. Seven true aneurysms, 1 false aneurysm, and 1 dissecting aneurysm were diagnosed with CTA in the 9 patients (mean age, 50.8±20.3 years; 1 male). The aneurysms were divided into two subgroups: 4 type I, and 5 type IIb according to a recent classification. Per schedule, 7 patients (4 type I and 3 type IIb) were treated with endovascular intervention, and 2 (type IIb) were treated with hybrid procedures. The technique success rate was 88.9%. One patient (type IIb) who was scheduled to be treated with an endovascular procedure was transferred to a hybrid procedure because of failure of the endovascular procedure. Eleven covered stents were implanted to exclude the aneurysms. During follow-up (mean duration 31.2±23.2 months), all aneurysms were proven excluded, no significant complication occurred, and preoperative symptoms resolved. One patient (type I) in the endovascular group had occlusion of the internal carotid artery but no symptoms; the internal carotid artery was patent in the other 8 patients. CONCLUSIONS: Hybrid and endovascular procedures were found effective and durable alternatives to open operation for treatment of extracranial juxta-skullbase carotid aneurysm.

Beclin1 Haploinsufficiency accentuates second-hand smoke exposure -induced myocardial Remodeling and contractile dysfunction through a STING-mediated mechanism.

Second-hand smoking evokes inflammation and cardiovascular diseases. Recent evidence has revealed a pivotal role for deranged autophagy in smoke exposure-induced cardiac anomalies. This study evaluated the impact of haploinsufficiency of the mTOR-independent autophagy protein Beclin1 on side-stream smoke exposure-induced cardiac anomalies and mechanism(s) involved. Adult WT and Beclin1 haploinsufficiency (Becn+/-) mice were exposed to cigarette smoke for 1 h daily for 90 days. Echocardiographic, cardiomyocyte function, intracellular Ca2+, autophagy, mitophagy, apoptosis and inflammation were examined. DHE staining was employed to evaluate O2- level. Our data revealed that Beclin1 deficiency exacerbated smoke exposure-induced myocardial anomalies in geometry, fractional shortening, cardiomyocyte function, intracellular Ca2+ handling, TEM ultrastructure, and inflammation along with pronounced apoptosis and O2- production. Side-stream smoke provoked excessive autophagy/mitophagy, mtDNA release, and activation of innate immune response signals cyclic GMP-AMP synthase (cGAS) and its effector - stimulator of interferon genes (STING), the effect was abolished or unaffected by Becn haploinsufficiency. STING phosphorylation was overtly promoted by smoke exposure in Becn+/- mice. Smoke exposure also suppressed phosphorylation of mTOR although it facilitated that of ULK1 in both groups. In vitro data revealed that inhibition of cGAS or STING failed to affect smoke extract-induced mitophagy although they abrogated smoke extract-induced cardiomyocyte dysfunction except cGAS inhibition in Becn+/- mice. These data suggest that Beclin1 is integral in the maintenance of cardiac homeostasis under side-stream smoke exposure via a STING-mediated mechanism.

Mid-term results of in situ fenestration stented with balloon-expandable bare metal stents during thoracic endovascular aortic repair.

PURPOSE: To assess the safety, feasibility and effectiveness of balloon-expandable bare metal stents (BMS) as bridge stents during thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Retrospective analysis was conducted on 103 consecutive patients who underwent TEVAR procedures from December 2015 to March 2018. Thirty-one patients fulfilled requirements for inclusion and exclusion in the analysis. Thirty-three in situ fenestration (ISF) procedures (single fenestration [n = 29]; dual fenestration [n = 2]) were performed in the 31 patients (67.7% men; median age, 61.5 year) who underwent TEVAR for thoracic lesions (aortic dissection [n = 23], aortic aneurysm [n = 3], aortic ulcer [n = 5]) with 34 stents (33 balloon-expandable BMS, 1 covered stents) implanted in supraaortic arteries. The success rate of overall intervention, fenestration, and implantation of BMS was recorded. The therapeutic effects and complications during admission and follow-up (median 29.7 months, range 18-45 months) were the primary outcomes. RESULTS: The technical success rate was 90.3% (28/31). All thoracic lesions were totally excluded. Major complications (6.5%) were one dissection in the left subclavian artery (n = 1) and thrombus formation (n = 1). Minor complications (12.9%) were hematoma (n = 1), and type III endoleak (n = 3). During follow-up, no endoleak developed and all fenestrated branch arteries were patent, except for one left subclavian artery dissection and occlusion. CONCLUSIONS: Use of balloon-expandable BMS in ISF is safe and effective in reconstruction of supraarotic arteries during TEVAR.

Cross-sectional associations of adipokines and abdominal fat distribution with aging in men.

OBJECTIVE: To investigate the relationship of adipokines and abdominal fat distribution with aging in men. METHODS: In a cross-sectional study, a total of 218 participants aged 40-79 years were recruited as a subset of the Prospective Urban Rural Epidemiology (PURE) China Action on Spine and Hip status (CASH) study population. Analysis of variance (ANOVA) and multivariable regression were used to estimate the associations of interest. RESULTS: With the increasing of age, waist circumference, waist-to-hip ratio, waist-to-height ratio, total adipose tissue (TAT), visceral adipose tissue (VAT), VAT/subcutaneous adipose tissue (SAT), leptin, adiponectin-to-leptin ratio, and human monocyte chemo-attractant protein-1 (MCP-1) increased significantly (p < 0.05), while adiponectin decreased significantly (p < 0.05). Adiponectin, adiponectin/leptin, and adiponectin/resistin varied inversely with the VAT quartiles (p < 0.05). There was a significant negative correlation among adiponectin, adiponectin-to-leptin ratio, adiponectin-to-resistin ratio, and all the body fat distribution parameters. VAT was inversely and significantly associated with adiponectin, adiponectin-to-leptin ratio, and adiponectin-to-resistin ratio (p < 0.05). CONCLUSIONS: It showed that aging, abdominal fat distribution, and adipokines were related with each other, which support the hypothesis that regulation of VAT and adipokines is closely linked to aging.

Age- and sex-related differences in muscle strength and physical performance in older Chinese.

BACKGROUND: Little is known about muscle strength and physical performance in Chinese. AIM: This study aimed to assess the age- and sex-related differences in muscle strength and physical performance in older Chinese. METHODS: Three hundred and eight healthy participants (110 males and 198 females) age 68.3 ± 6.1 (mean ± SD) years were enrolled in this cross-sectional study. The handgrip muscle strength (HGS) of the dominant hand was measured using a Jamar dynamometer. Physical performance was assessed by the Timed Up and Go test (TUG). The EuroQol five-dimension questionnaire (EQ-5D) was used to evaluate participants' health status. RESULTS: Men showed higher levels of HGS with a smaller percentage having low muscle strength compared with women. No differences were observed in TUG between sexes. No significant association of TUG and age was observed in males. However, older females had increased TUG and hence poorer performance. Good health status was associated with better physical performance but was not related to muscle strength in either sex. DISCUSSION: In men, there was no correlation between age and TUG, although a negative association with handgrip muscle strength was observed. For women, both muscle strength and physical performance declined with age. The sex-related differences in aging effects on physical performance in our study could partly explain why women have a higher incidence of hip fracture than men. CONCLUSION: Chinese women may be more vulnerable to severe sarcopenia in old age than men.

Assessing the potential risk and relationship between microplastics and phthalates in surface seawater of a heavily human-impacted metropolitan bay in northern China.

The impacts of microplastics (MPs) and phthalates (PAEs), a class of MP-associated contaminants, on the marine environment are not thoroughly understood despite concern over their adverse effects on humans and ecosystems. Field studies linking MPs and PAEs in seawater have not yet been reported. We investigate for the first time the correlation between MPs contamination and the presence of PAEs in the surface seawater of Jiaozhou Bay (JZB), a semi-enclosed metropolitan bay in northern China heavily impacted by human activity. The abundance of MPs, dominated by polyethylene and polyethylene terephthalate mostly smaller than 2 mm, ranged between 24.44 items/m3 and 180.23 items/m3, with the majority being black and transparent fibers and fragments. Concentrations of PAEs varied from 129.96 ng/L to 921.22 ng/L. Relatively higher abundances of MPs and higher concentrations of PAEs were generally found in areas near riverine inputs and sewage treatment plants. There was a strong correlation between PAEs concentration and MPs abundance, suggesting that they are closely linked. In a risk assessment combining PAEs and MPs, the risk quotients (RQs) indicated that the ecological risk of di-n-butyl phthalate in JZB was relatively high (0.046

A Single-Center, Randomized, Controlled Comparison of the Transradial vs Transfemoral Approach for Cerebral Angiography: A Learning Curve Analysis.

Purpose: To compare the characteristics and learning curve of the transfemoral approach (TFA) vs the transradial approach (TRA) for cerebral angiography. Materials and Methods: Between February 2016 and April 2017, 101 patients undergoing cerebral angiography were enrolled. Fifty-one patients (mean age 67 years; 40 men) were randomized to TFA and 50 (mean age 68 years; 41 men) to TRA using a computer-generated random table. The patients' demographic and angiographic data were recorded and analyzed. The learning curve of a novice interventionist was analyzed for procedure time, puncture time, fluoroscopy time, and contrast volume as markers of technical proficiency with TFA compared with TRA. Median values are given with the interquartile range (IQR). Results: Procedure time [35 (IQR 30, 47.5) vs 31.0 (IQR 25.0, 48.9) minutes, p=0.16), fluoroscopy time [10.3 (IQR 7.6, 13.9) vs 9.4 (IQR 6.1, 17.6) minutes, p=0.70], contrast volume [105 (IQR 92, 120) vs 95.5 (IQR 90, 111.3) mL, p=0.13), radiation exposure [390.2 (IQR 268.2, 617.9) vs 455.8 (IQR 286.8, 602.3) mGy, p=0.74], and the number of catheter exchanges [1 (IQR 1, 3) vs 1 (IQR 1, 1), p=0.06] were not significantly different between the TFA and TRA groups, respectively, but puncture time was shorter with TFA than with TRA [0.6 (IQR 0.5, 1.1) vs 1 (IQR 0.6, 1.9) minutes, p=0.01]. The learning curve was steeper with TRA than with TFA in the beginning stages of training, but with increasing experience, the procedure and fluoroscopy times were better for TRA than for TFA. Training progress was made earlier in TRA. Conclusion: TRA is a reasonable alternative to TFA for cerebral angiography. TRA has a shorter learning curve for novice interventionists.

Matrix metalloproteinases are regulated by MicroRNA 320 in macrophages and are associated with aortic dissection.

Aortic dissection (AD) is the circumferential or transversal tear of the aorta wall that allows blood to infiltrate the layers. MicroRNA (miR) analyses have demonstrated a correlation between miR-320 family and AD. The underlying mechanism is yet unclear. The matrix metalloproteinases (MMPs) are a group of proteolytic enzymes that could catalyze the degeneration of the extracellular matrix and the destruction of the vasculature. In this study, we investigated whether miR-320 presented a role in regulating the production of MMPs in aortic dissection. In a cohort of 30 CE patients and 30 healthy controls, the transcription and secretion of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-12 by monocytes were investigated. The monocyte from AD patients presented significantly elevated capacity of MMP expression than those from healthy controls. In contrast, the monocyte/macrophage expression of miR-320 was significantly lower in AD patients than in controls. In both AD patients and healthy controls, LPS-activation of macrophages resulted in MMP upregulation and miR-320 downregulation, in which the MMP expression was significantly higher while the miR-320 expression was significantly lower in AD patients than in healthy controls. Transfection of miR-320 mimic did not affect MMP gene transcription but significantly reduced the protein production in some MMPs, demonstrated that miR-320 were involved in the post-transcriptional regulation of MMPs. Together, these results demonstrated that miR-320 could regulate the expression of MMPs by macrophages, through which miR-320 may interfere with AD development.