Eccentricity-paced geomagnetic field and monsoon rainfall variations over the last 870 kyr.

Whether there are links between geomagnetic field and Earth's orbital parameters remains unclear. Synchronous reconstructions of parallel long-term quantitative geomagnetic field and climate change records are rare. Here, we present 10Be-derived changes of both geomagnetic field and Asian monsoon (AM) rainfall over the last 870 kyr from the Xifeng loess-paleosol sequence on the central Chinese Loess Plateau. The 10BeGM flux (a proxy for geomagnetic field-induced 10Be production rate) reveals 13 consecutive geomagnetic excursions in the Brunhes chron, which are synchronized with the global records, providing key time markers for Chinese loess-paleosol sequences. The 10Be-derived rainfall exhibits distinct ~100 kyr glacial-interglacial cycles, and superimposed precessional (~23 kyr) cycles that match with those in Chinese speleothem δ18O record. We find that changes in the geomagnetic field and AM rainfall share a common ~100 kyr cyclicity, implying a likely eccentricity modulation of both the geomagnetic field and climate.

DNMT1-induced miR-133b suppression via methylation promotes myocardial fibrosis after myocardial infarction.

Myocardial fibrosis is an underlying cause of many cardiovascular diseases. Novel insights into the epigenetic control of myocardial fibrosis are now emerging. The current work is focused on investigating the biological role of DNA methyltransferase 1 (DNMT1) in myocardial fibrosis as well as the underlying mechanism. Our findings revealed that DNMT1 expression levels were upregulated, whereas miR-133b expression levels were decreased in a rat model of myocardial fibrosis following myocardial infarction. In vitro, the expression levels of DNMT1 increased and those of miR-133b decreased after Ang-II treatment in cardiac fibroblasts. DNMT1 knockdown inhibited Ang-II-induced cardiac myofibroblast activation, and DNMT1 overexpression increased the proliferation and collagen generation of cardiac myofibroblasts. Furthermore, DNMT1 expression levels decreased, while miR-133b expression levels increased after treatment with 5-Aza (5-Azacytidine, a known inhibitor of DNA methylation) in Ang-II-induced cardiac fibroblasts. BSP (Bisulfite sequencing PCR) results showed a marked decrease in methylation levels in the miR-133b promoter region upon overexpression of DNMT1, whereas knockdown of DNMT1 blocked increased methylation levels in the miR-133b promoter region in Ang-II-induced cardiac fibroblasts. Finally, 5-Aza treatment reduced the progression of myocardial fibrosis after myocardial infarction in rats in vivo. Collectively, our results suggest that DNMT1 mediates CTGF expression in cardiac fibroblast activation by regulating the methylation of miR-133b. The present work reveals the unique role of the DNMT1/miR-133b/CTGF axis in myocardial fibrosis, thus suggesting its great therapeutic potential in the treatment of cardiac diseases.

Efficacy and Safety of Left Atrial Appendage Occlusion in Mild Mitral Stenosis Patients with High Bleeding Risk.

Atrial fibrillation (AF) is highly prevalent in patients with mitral stenosis (MS), but the efficacy of left atrial appendage occlusion (LAAO) in these patients remains unclear.The aim of this study was to evaluate the efficacy and safety of LAAO in patients with MS complicated by AF at high risk of bleeding.We recruited patients from September 2015 to September 2018. We compared the 3-year outcomes of LAAO in 21 patients with AF complicated by MS and 42 sex- and age-matched patients with AF without MS.The MS group had more cases of peripheral arterial embolism (28.6% versus 2.4%, P = 0.004), more spontaneous echo contrast (47.6% versus 9.5%, P = 0.001), a larger LAA orifice diameter (P < 0.01), and a slower LAA flow (P < 0.05) than the Non-MS group. The mean size of the selected occluder device was bigger for patients with MS than for patients with Non-MS (29.2 ± 3.7 versus 26.9 ± 3.1 mm, P = 0.014). In the first 45 follow-up days, 2 (9.5%) patients with MS had device-related thrombi (DRT); one of them had transient ischemic attack 24 hours postoperatively. From 45 days to 6 months, one patient in each group had DRT. After 6 months, two patients in the Non-MS group still had residual leaks; one of them had a stroke, with a small DRT. The proportion of dual antiplatelet therapy was higher in the Non-MS group than in the MS group (33.3% versus 4.8%, P = 0.012), but this population had an increased bleeding risk.LAAO is relatively effective and safe for preventing embolic events in patients with MS complicated by AF, at high risk of bleeding.

Development and validation of a novel pseudogene pair-based prognostic signature for prediction of overall survival in patients with hepatocellular carcinoma.

BACKGROUND: There is growing evidence that pseudogenes may serve as prognostic biomarkers in several cancers. The present study was designed to develop and validate an accurate and robust pseudogene pairs-based signature for the prognosis of hepatocellular carcinoma (HCC). METHODS: RNA-sequencing data from 374 HCC patients with clinical follow-up information were obtained from the Cancer Genome Atlas (TCGA) database and used in this study. Survival-related pseudogene pairs were identified, and a signature model was constructed by Cox regression analysis (univariate and least absolute shrinkage and selection operator). All individuals were classified into high- and low-risk groups based on the optimal cutoff. Subgroups analysis of the novel signature was conducted and validated in an independent cohort. Pearson correlation analyses were carried out between the included pseudogenes and the protein-coding genes based on their expression levels. Enrichment analysis was performed to predict the possible role of the pseudogenes identified in the signature. RESULTS: A 19-pseudogene pair signature, which included 21 pseudogenes, was established. Patients in high-risk group demonstrated an increased the risk of adverse prognosis in the TCGA cohort and the external cohort (all P < 0.001). The novel pseudogene signature was independent of other conventional clinical variables used for survival prediction in HCC patients in the two cohorts revealed by the multivariate Cox regression analysis (all P < 0.001). Subgroup analysis further demonstrated the diagnostic value of the signature across different stages, grades, sexes, and age groups. The C-index of the prognostic signature was 0.761, which was not only higher than that of several previous risk models but was also much higher than that of a single age, sex, grade, and stage risk model. Furthermore, functional analysis revealed that the potential biological mechanisms mediated by these pseudogenes are primarily involved in cytokine receptor activity, T cell receptor signaling, chemokine signaling, NF-κB signaling, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. CONCLUSION: The novel proposed and validated pseudogene pair-based signature may serve as a valuable independent prognostic predictor for predicting survival of patients with HCC.

Feasibility of Device Closure for Multiple Atrial Septal Defects With an Inferior Sinus Venosus Defect: Procedural Planning Using Three-Dimensional Printed Models.

BACKGROUND: Multiple atrial septal defects (ASD) with an inferior sinus venosus defect (SVD) have always been considered to be contraindications for interventional therapy. On the basis of early experience using a patent ductus arteriosus (PDA) occluder for interventional treatment for inferior ASD, this study investigated the feasibility of transcatheter closure of multiple ASDs with an inferior SVD under the guidance of three-dimensional (3D) printed heart models. METHODS: Between August 2016 and February 2017, five patients who were diagnosed with multiple ASDs with an inferior SVD at the First Affiliated Hospital of Xi'an Jiaotong University underwent cardiac computed tomography (CT) scans and three-dimensional (3D) echocardiography to generate heart disease models by a 3D printing technique. The best occlusion program was determined through a simulated closure on the model. Percutaneous device closure of multiple ASDs with an inferior SVD was performed following the predetermined program, guided only by fluoroscopy. Follow-up included electrocardiography, transthoracic echocardiography, and transoesophageal echocardiography. RESULTS: Three-dimensional (3D) printed models for all five patients were produced successfully. Four (4) patients had a secundum ASD with an inferior sinus venosus ASD, and one patient had a patent foramen ovale (PFO) with an inferior sinus venosus ASD. All patients were successfully treated with interventional therapy. Inferior sinus venosus ASD was percutaneously closed using the PDA occluder, and the additional secundum ASD or PFO in each patient was percutaneously closed using an ASD or PFO occluder at the same time. There was no device embolisation, procedure-related death or pericardial tamponade. During the 1-year follow-up, a minor residual shunt was detected in one patient. CONCLUSION: The use of 3D printed ASD models provides a useful reference for transcatheter device closure of multiple ASD with an inferior SVD. This approach can provide a new treatment strategy for inferior sinus venosus ASD, which has been considered a contraindication for interventional therapy. However, long-term follow-up in a large number of patients is still warranted.

Association between the CD14-260C>T gene polymorphism and susceptibility to myocardial infarction: Evidence from case-control studies.

Numerous published studies have investigated the relationship between the CD14-260C>T (rs2569190) polymorphism and the risk of myocardial infarction (MI). However, the results are still conflicting and inconclusive. Potentially eligible published articles were searched in four databases including PubMed, Web of Science, EMBASE and Chinese Biomedical Database (CBM). The odds ratio (OR) with its 95% confidence interval (CI) was used to estimate the strength of the associations. Thirteen papers including 17 case-control studies were included, reporting a total of 6,443 MI patients and 6,315 controls. A significant increase in overall MI susceptibility was identified in the homozygote model. In the subgroup analysis, with respect to the type of MI, a significantly increasing acute MI susceptibility was found in the homozygote model. In the subgroup analysis for ethnicity, a significant increased susceptibility was found in Asian populations in allele, homozygote, recessive and dominant models. However, no significant association was found among Caucasian populations. In conclusion, there may be a moderate association between the CD14-260C>T polymorphism and acute MI susceptibility. This association may be different between ethnicities with the CD14-260C>T polymorphism being a risk factor for myocardial infarction in Asian populations.

Multidisciplinary assessment of PFO with substantial right-to-left shunting and medium-term follow-up after PFO device closure: A single-center experience.

OBJECTIVES: To describe the multidisciplinary assessment of patent foramen ovale (PFO) with substantial right-to-left shunting (RLS) and medium-term follow-up after PFO closure for stroke or transient ischemic attack (TIA). BACKGROUND: PFO closure is a therapeutic option to prevent recurrent ischemic event in patients with cryptogenic stroke and TIA. The apparent lack of benefit seen in previous studies was in part due to the inclusion of patients with alternate mechanisms of stroke/TIA. However, the long-term follow-up results of RESPECT trial confirmed that PFO closure could reduce the recurrence rate of stroke compared to medical therapy. The obvious difference between RESPECT and the other studies is that RESPECT recruited more relevant patients with substantial RLS. METHODS: From May 2013 to October 2015, all subjects diagnosed as cryptogenic stroke or TIA with substantial RLS who underwent PFO closure at our institution were included. All patients underwent multidisciplinary assessment to exclude stroke/TIA with definite etiology. Baseline characteristics, clinical manifestations, procedural, and follow-up data were reviewed. RESULTS: A total of 219 consecutive patients with substantial RLS undergoing PFO closure were identified. There were no procedure-related deaths, strokes, or TIA. Mean follow-up was 2.0 ± 0.7 years. Early residual shunting was visible in 9 patients (4.1%); however, during follow-up, only 3 patients (1.4%) had residual RLS detected by contrast transthoracic echocardiography (cTTE). The annual risk of recurrent ischemic stroke or TIA was 0.457%. CONCLUSIONS: PFO closure can be performed safely and effectively in patients with cryptogenic stroke or TIA. In selected patients with substantial RLS, following appropriate multidisciplinary assessment, excellent results with low incidence of recurrent events may be achieved.

A Case Report on Pulmonary Arteriovenous Fistula with Recurrent Cerebral Infarction.

Patent foramen ovale (PFO) and pulmonary arteriovenous fistula (PAVF) have been both proposed as a mechanism for cerebral infarction. However, there are only a few reports on how to distinguish the role of the two factors in cerebral infarction.

Faster super-resolution imaging of high density molecules via a cascading algorithm based on compressed sensing.

This paper proposes a cascading algorithm (CSR) based on compressed sensing, which aims to reduce intensive computations in super-resolution imaging of fluorescence microscopy. Performance of existing algorithms such as CVX and L1H drop sharply when applied to obtain finer images with high density molecules. CSR fully exploits the extreme sparsity property of molecules in the compressed sensing model and progressively restricts solution space stage by stage. We perform a comprehensive study of existing algorithms and the proposed algorithm under different resolutions and molecules' densities. Simulation and experimental results confirm the performance advantage of CSR when applied to recover dense molecules.

[The effect of oversized occluder on endothelialization after percutaneous closure of experimental atrial septal defect in dogs].

OBJECTIVE: To observe the effect of oversized occluder on endothelialization post percutaneous closure of experimental atrial septal defect (ASD) in dogs. METHODS: ASD was established with the help of transthoracic echocardiography in 18 dogs. ASD size was (6.0 ± 0.2) mm. Dogs were randomly divided into normal size group (implanted with 8 mm occlude, n = 9) and oversized group (implanted with 12 mm occluder, n = 9). Dogs were randomly killed at 3, 6 and 14 months after percutaneous closure. The endothelialization process on device surface was observed by scanning electron microscope. RESULTS: Four animals died around 1 month post procedure. Microscopic sections from normal group showed nearly complete endothelialization at 3 months after device implantation and complete endothelialization at 6 and 14 months after device implantation. While microscopic sections showed lack of endothelialization at 3 months post implantation, nearly endothelialization at 6 months, and complete endothelialization at 14 months after device implantation in oversized group. CONCLUSION: Incomplete endothelialization of occluder surface is observed at 6 months after implantation of an oversized ASD occluder device in this model.

The relationship between C-reactive protein to lymphocyte ratio and the prevalence of myocardial infarction in US adults: A cross-sectional study.

Objective: C-reactive protein to lymphocyte ratio (CLR) has been identified as a novel inflammatory biomarker. However, the role of CLR in myocardial infarction is unclear. Thus, this study designs to investigate the association of CLR with the prevalence of myocardial infarction in a large multiracial population in the United States. Methods: Participants from the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 Pre-pandemic were included in this cross-sectional study. Multivariable regression and subgroup analyses, controlling for demographic variables, were performed to examine the association between CLR and its quintiles and myocardial infarction. A smooth curve fitting was used to model the non-linear relationship between them. Results: A total of 12,615 participants aged ≥18 years were recruited, of whom 609 (4.83%) self-reported a history of myocardial infarction. Compared to those in the lowest quartile of ln-transformed CLR (Q1), the myocardial infarction risks for subjects in Q2, Q3, and Q4 were 1.64, 1.71, and 1.79 times, respectively. Obvious upward trends were observed when ln-transformed CLR increased (P for trend <0.01). In continuous analyses, the fully adjusted odds ratios (OR) for myocardial infarction prevalence per ln-transformed increment in CLR was 1.46 (95% CI: 1.16-1.84, P < 0.01). Furthermore, a linear association was detected for ln-transformed CLR with the risk of myocardial infarction. Interaction test showed that the effect of CLR on myocardial infarction was significantly affected by age (P for interaction = 0.04). Conclusions: Data from a large, cross-sectional cohort program show that CLR is positively associated with myocardial infarction prevalence. Our findings highlight that CLR may be a novel inflammation warning biomarker for myocardial infarction.

Relieving Compression-Induced Local Wear on Non-Volatile Memory Block via Sliding Writes.

Due to its non-volatility and large capacity, NVM devices gradually take place at various levels of memories. However, their limited endurance is still a big concern for large-scale data centres. Compression algorithms have been used to save NVM space and enhance the efficiency of those lifetime extension methods. However, their own influence on the NVM lifetime is not clear. In order to fully investigate the impact of compression on NVM, this paper first studies bit flips involved in several typical compression algorithms. It is found that more bit flips would happen in the shrunken area of a memory block. This induces the phenomenon of intra-block wear unevenness, which sacrifices NVM lifetime. We propose a new metric called local bit flips to describe this phenomenon. In order to relieve the intra-block wear unevenness caused by compression, this paper proposes a sliding write method named SlidW to distribute the compressed data across the whole memory block. We first divide the memory block into several areas, and then consider five cases about the relationship between new data size and left space. Then, we place the new data according to the case. Comprehensive experimental results show that SlidW can efficiently balance wear and enhance NVM lifetime.

Transjugular Approach to Closure of Patent Foramen Ovale Under the Guidance of Fluoroscopy and Transthoracic Echocardiography: A Case Report.

Background: We describe a rare case of patent foramen ovale (PFO) associated stroke in a patient with pulmonary embolism, inferior vena cava thrombosis and undergoing filter implantation who successfully underwent PFO closure using the right internal jugular venous approach. Case Summary: This is a rare case of a 42-year-old patient who presented with stroke and pulmonary embolism and was diagnosed with a PFO, inferior vena cava thrombosis and underwent filter implantation. The patient suffered from stroke and pulmonary embolism successively; that is, embolic events occurred in both the arterial and venous systems. Transesophageal echocardiography (TEE) showed a PFO with an atrial septal aneurysm (ASA), which we considered a "pathological" PFO. Due to the obstructive nature of the inferior vena cava approach, we successfully performed PFO closure via the right internal jugular venous approach under the guidance of X-ray and transthoracic echocardiography (TTE). Discussion: The right jugular venous approach provides a simple technical solution for patients who require PFO closure when femoral venous access is unavailable, which can be performed under X-ray and TTE guidance.

A Prospective, Single-Center, Phase I Clinical Trial to Evaluate the Value of Transesophageal Echocardiography in the Closure of Patent Foramen Ovale With a Novel Biodegradable Occluder.

Objective: Traditional metal alloy occluders for the closure of patent foramen ovale (PFO) may be associated with some potential complications, and may restrict the trans-septal access to the left atrium for future treatment of left-sided heart disease. Increasing attention has been paid to novel biodegradable occluders (NBOs) to achieve PFO closure. We aimed to evaluate the role of transesophageal echocardiography (TEE) in the diagnostic and anatomical evaluation of PFO, as well as in the Post-procedural assessment after transcatheter closure with a NBO. Methods: We conducted a prospective, single-center clinical study of 44 patients who were diagnosed with PFO by contrast transthoracic echocardiography (c-TTE) and TEE from June 2019 to June 2020. All patients underwent PFO occlusion with NBO under TTE guidance. Follow-up was performed at 2 days and 3 months after the procedure with TTE, and at 6 months and 1 year after the procedure with c-TTE, TTE, and TEE. Results: Interventional treatment was successfully performed in all patients. The left and right sides of the occluder device disc were significantly reduced at 3, 6, and 12 months compared to 2 days after the procedure (all P < 0.01), and decreased gradually. The thickness was significantly reduced at 12 months compared to the first three time points (all P < 0.01). Thrombus was found on the surface of the occluder device in three patients (6.4%) at 3 and 6 months after occlusion. At 6 months after procedure, there were 3 (6.8%) cases of extensive residual right-to-left shunt (RLS), 2 (4.5%) cases of moderate shunt, and 7 (15.9%) cases of small shunts. One year after procedure, 2 (4.5%) cases had a extensive residual shunt, 6 (13.6%) cases of small shunts were confirmed to originate from pulmonary veins by TEE, and the PFO-RLS occlusion rate reached 95.5%. Conclusion: This study demonstrates the feasibility, safety, and effectiveness of NBO for the closure of PFO in humans, with a high rate of complete shunt closure. Accurate TEE assessment of the PFO anatomy before closure with NBO is important to ensure that the procedure remains safe and effective. Furthermore, TEE plays a crucial role in the Post-procedure follow-up.

Application of Transesophageal Echocardiography in Amplatzer Atrial Septal Defect Occluder for Percutaneous Closure of Large Patent Foramen Ovale.

Objective: The Amplatzer patent foramen ovale (PFO) occluder is the most commonly used device for percutaneous closure of a large PFO. However, its use may predispose the patient to postoperative residual shunting. To reduce the incidence of residual shunting, we investigated the safety and effectiveness of the Amplatzer atrial septal defect (ASD) occluder for percutaneous closure of a large PFO measured by transesophageal echocardiography (TEE) and evaluated the value of TEE in this procedure. Methods: Overall, 118 patients who were diagnosed with a large PFO (all with a ≥ 2 mm left atrial side height after the Valsalva maneuver (VM) excluding those with a small ASD) using contrast transthoracic echocardiography (c-TTE) and TEE underwent closure under TEE guidance at The First Affiliated Hospital of Xi'an Jiaotong University. An ASD device was used in 48 patients (group I) and a PFO device in 70 (group II). After the procedure, we verified the safety and efficacy of different devices using c-TTE, TTE, and TEE. Results: In both groups, the preoperative TEE results showed a significantly increased left height of the PFO after VM compared with that at rest (all P < 0.01). Compared with the left height of the PFO measured using TEE after VM, the PFO-stretch diameter (SD) measured by TEE after the delivery sheath passed the PFO was higher (all P < 0.01). We selected the ASD occluder size according to this PFO-SD. In group II, most patients underwent the implantation of the larger PFO devices. Interventional treatment was successfully performed on all patients. The effective occlusion rate in group I at 12 months after the procedure was significantly higher than that in group II (93.7% vs. 78.6%, P < 0.05). The TEE results showed that 18 patients with a medium and large residual shunt at 12 months after the procedure exhibited an intradisc tunnel-like shunt. Conclusion: The Amplatzer ASD device and Amplatzer PFO device are safe for large PFO closure, but the Amplatzer ASD device has a higher effective occlusion rate. TEE plays a crucial role in the use of the Amplatzer ASD occluder for percutaneous closure of a large PFO.

Observation and Optimization on Garbage Collection of Flash Memories: The View in Performance Cliff.

The recent development of 3D flash memories has promoted the widespread application of SSDs in modern storage systems by providing large storage capacity and low cost. Garbage collection (GC) as a time-consuming but necessary operation in flash memories largely affects the performance. In this paper, we perform a comprehensive experimental study on how garbage collection impacts the performance of flash-based SSDs, in the view of performance cliff that closely relates to Quality of Service (QoS). According to the study results using real-world workloads, we first observe that GC occasionally causes response time spikes, which we call the performance cliff problem. Then, we find that 3D SSDs exacerbate the situation by inducing a much higher number of page migrations during GC. To relieve the performance cliff problem, we propose PreGC to assist normal GC. The key idea is to distribute the page migrations into the period before normal GC, thus leading to a reduction in page migrations during the GC period. Comprehensive experiments with real-world workloads have been performed on the SSDsim simulator. Experimental results show that PreGC can efficiently relieve the performance cliff by reducing the tail latency from the 90th to 99.99th percentiles while inducing a little extra write amplification.

Application-Oriented Data Migration to Accelerate In-Memory Database on Hybrid Memory.

With the advantage of faster data access than traditional disks, in-memory database systems, such as Redis and Memcached, have been widely applied in data centers and embedded systems. The performance of in-memory database greatly depends on the access speed of memory. With the requirement of high bandwidth and low energy, die-stacked memory (e.g., High Bandwidth Memory (HBM)) has been developed to extend the channel number and width. However, the capacity of die-stacked memory is limited due to the interposer challenge. Thus, hybrid memory system with traditional Dynamic Random Access Memory (DRAM) and die-stacked memory emerges. Existing works have proposed to place and manage data on hybrid memory architecture in the view of hardware. This paper considers to manage in-memory database data in hybrid memory in the view of application. We first perform a preliminary study on the hotness distribution of client requests on Redis. From the results, we observe that most requests happen on a small portion of data objects in in-memory database. Then, we propose the Application-oriented Data Migration called ADM to accelerate in-memory database on hybrid memory. We design a hotness management method and two migration policies to migrate data into or out of HBM. We take Redis under comprehensive benchmarks as a case study for the proposed method. Through the experimental results, it is verified that our proposed method can effectively gain performance improvement and reduce energy consumption compared with existing Redis database.

Adults with current asthma but not former asthma have higher all-cause and cardiovascular mortality: a population-based prospective cohort study.

Higher mortality in asthmatics has been shown previously. However, evidence on different asthma phenotypes on long-term mortality risk is limited. The aim was to evaluate the impact of asthma phenotypes on mortality in general population. Data from the National Health and Nutrition Examination Survey from 2001-2002 to 2013-2014 linked mortality files through December 31, 2015, were used (N = 37,015). Cox proportional hazards regression was used to estimate the risk of all-cause and cause-specific mortality adjusting for sociodemographic characteristics, smoking, body mass index, and chronic conditions. During the mean follow-up time of 7.5 years, 4326 participants died from a variety of causes. Current asthma, but not former asthma was associated with increased all-cause mortality (current asthma: HR = 1.37; 95% CI 1.20-1.58; Former asthma: HR = 0.93; 95% CI 0.73-1.18); as well as mortality from cardiovascular disease (HRCurrent = 1.41; 95% CI 1.08-1.85) and chronic lower respiratory diseases (HRCurrent = 3.17; 95% CI 1.96-5.14). In addition, we found that the HR for cardiovascular disease (CVD) mortality was slightly greater in people with childhood-onset asthma than those with adult-onset asthma. The HR for chronic lower respiratory diseases (CLRD) mortality was greater in people with adult-onset asthma than those with childhood-onset asthma. However, the differences were not statistically significant. Our study suggested that current asthma but not former asthma was associated with increased all-cause, CLRD and CVD mortality. Future well-designed studies with larger sample are required to demonstrate the association and clarify the potential mechanisms involved.

Efficacy of patent foramen ovale closure for treating migraine: a prospective follow-up study.

This study aims to evaluate the potential of percutaneous patent foramen ovale (PFO) closure to improve the headache in patients with migraine and PFO, and discuss the difference between the randomized controlled trials (RCTs) and the single-center studies. Patients of migraine with a large shunt of PFO, who experienced ≥2 headache attacks per month and failed ≥2 categories of standardized medication, underwent PFO closure in First Affiliated Hospital of Xi'an Jiao Tong University. The clinical outcomes, including frequency and duration of headache attacks, Headache Impact Test (HIT-6) score, and Visual Analogue Scale (VAS) score, were evaluated at 3, 6, and 12 months of follow-up after the PFO closure. The different efficacies of the clinical outcomes between patients with and without aura as well as different grades of PFO were also evaluated, respectively. 134 patients with migraine (39 male and 95 female) with PFO were enrolled, whose average age was 39.21±11.37 years. After PFO closure, there was a significant reduction in frequency and duration of headache attacks, HIT-6 score, and VAS score at 3, 6, and 12 months' follow-up (p<0.001). Migraine was completely relieved in 54 (40.30%) patients during 12 months' follow-up. The frequency of migraine was reduced by >50% in 44 (32.84%) patients at 3 months' follow-up and increased to 48 (35.82%) at 12 months' follow-up. 31.03% patients remained residual shunt after 6 months of closure with varying improvements of headache. This study confirmed that PFO closure can effectively reduce frequency and duration of migraine and improve quality of life, but the definitive indications and long-term effect still need further research.

Importance of Persistent Right-to-Left Shunt After Patent Foramen Ovale Closure in Cryptogenic Stroke Patients.

Percutaneous closure of patent foramen ovale (PFO) is widely performed to prevent recurrent stroke or transient ischemic attack in patients with cryptogenic stroke. However, the influence of different degrees of right-to-left shunting (RLS) has rarely been reported. We retrospectively evaluated the cases of 268 patients with cryptogenic stroke who underwent PFO closure at our hospital from April 2012 through April 2015. In accordance with RLS severity, we divided the patients into 2 groups: persistent RLS during normal breathing and the Valsalva maneuver (n=112) and RLS only during the Valsalva maneuver (n=156). Baseline characteristics, morphologic features, and procedural and follow-up data were reviewed. The primary endpoint was stroke or transient ischemic attack. More patients in the persistent group had multiple or bilateral ischemic lesions, as well as a larger median PFO diameter (2.5 mm [range, 1.8-3.9 mm]) than did patients in the Valsalva maneuver group (1.3 mm [range, 0.9-1.9 mm]) (P <0.001). Atrial septal aneurysm was more frequent in the persistent group: 25 patients (22.3%) compared with 18 (11.5%) (P=0.018). Three patients in the persistent group had residual shunting. The annual risk of recurrent ischemic stroke was similar between groups: 0.298% (persistent) and 0.214% (Valsalva maneuver). Our findings suggest that patients with persistent RLS have more numerous severe ischemic lesions, larger PFOs, and a higher incidence of atrial septal aneurysm than do those without. Although our persistent group had a greater risk of residual shunting after PFO closure, recurrence of ischemic events did not differ significantly from that in the Valsalva maneuver group.