Search

BackgroundAbdominal aortic calcification (AAC) is a prevalent form of vascular calcification associated with adverse cardiovascular outcomes. While previous studies on AAC and cardiovascular risk exist, many have limitations such as small sample sizes and limited clinical significance outcomes. This study aims to prospectively investigate the association between AAC and all-cause and cardiovascular disease (CVD)-specific mortality rates in a nationally representative sample of adults in the United States, using data from the National Health and Nutrition Examination Survey (NHANES).MethodsThe study, conducted on NHANES participants aged 40 years or older during the 2013-2014 cycle, assessed AAC using the Kauppila scoring system. Demographic characteristics, mortality data, and comorbid factors such as age, gender, diabetes, and hypertension were considered. Statistical analyses, including weighted percentages, Kaplan-Meier survival curves, and multivariable Cox proportional hazards regression models, were employed to evaluate the associations between AAC and mortality risks.ResultsAfter analyzing a final sample of 2717 participants, the study found a significant association between severe AAC (SAAC) and higher all-cause mortality risk (HR 1.70, 95% CI 1.17-2.48). The dose-response relationship indicated an increased risk with higher AAC scores. However, no independent association was observed between AAC and cardiovascular mortality. Stratified analysis revealed variations in the AAC-all-cause mortality association based on gender and hypertension.ConclusionThis population-based study provides valuable insights into the prospective association between AAC and all-cause mortality, emphasizing the potential role of AAC assessment in identifying individuals at higher risk.

BackgroundThe impact of moderate-to-vigorous physical activity (MVPA) on all-cause mortality in type 2 diabetes (T2D) patients with severe abdominal aortic calcification (SAAC) remains unclear.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014, including T2D patients aged 40 years and older. AAC was assessed using the Kauppila scoring system, with SAAC defined as a score >6. Self-reported MVPA was categorized based on weekly minutes of activity. The weighted Cox regression model was used to investigate risk associations.ResultsAmong the weighted sample of 20,328,606 T2D participants, 16.39% had SAAC. SAAC was significantly associated with increased all-cause mortality (HR 2.57, 95% CI 1.52-4.35) after adjusting for confounders. MVPA did not significantly reduce mortality risk in patients with SAAC (HR 1.00, 95% CI 0.40-2.49).ConclusionSAAC is a robust predictor of mortality in T2D patients, and MVPA does not improve mortality outcomes in this high-risk group. Future studies should conduct more detailed subgroup analyses to identify the specific indications for MVPA.

Abstract Background A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction. Methods Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures. Results Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14–4.16%), below the literature-defined performance goal of 11% (P

Objective To investigate the factors influencing interbody cage subsidence after stand-alone oblique lumbar interbody fusion (OLIF). Methods A total of 65 patients (72 lumbar vertebrae) who underwent OLIF in our hospital from Ja-nuary 2019 to January 2023 were selected and divided into subsidence group (n=19) and non-subsidence group (n=53) according to the loss of disc height. The clinical data of the two groups were collected and compared, including gender, age, body mass index, number of lumbar vertebrae requiring surgery, responsible vertebral endplate sclerosis, cage height and length, preoperative CT values of the responsible vertebral body and its upper and lower endplates, preoperative multifidus muscle cross-sectional area at responsible vertebral body, degree of multifidus muscle atrophy, and degree of preoperative articular process degeneration. Logistic regression analysis was used to explore the factors influencing cage subsidence. Results There were significant differences between the two groups in the preoperative CT values of responsible vertebral body and its upper endplate, the proportion of patients with preoperative responsible vertebral body endplate sclerosis, the preoperative multifidus muscle cross-sectional area at responsible vertebral body, the proportion of patients with preoperative severe atrophy of the multifidus muscle, the proportion of patients with cage height 14 mm, the proportion of patients with cage length 55 mm, and the proportion of patients with articular process degeneration of degree 3 (t=2.332-3.097,χ2=4.545-6.246,P

Abstract The colloidal borescope, using colloidal particle motion, is used to monitor the flow velocities and directions of groundwater. It integrates advanced techniques such as microscopy, high-speed photography, and big data computing and enjoys high sensitivity at the micron level. However, In the same well, the groundwater flow velocity monitored by colloidal hole mirror is varies greatly from that obtained by conventional hydrogeological monitoring, such as pumping test. In order to solve this problem, the stability catcher and stratified packer are designed to control the interference of the vertical flow in drilling, and to monitor the flow velocity and direction of groundwater velocity at the target aquifer and target fracture. Five wells with different aquifers and different groundwater types were selected for monitoring in south-central China. The instantaneous velocity and direction are converted into east–west component and north–south component, the average velocity and direction is calculated according to the time of 10 min, and the particle trajectory diagram is established. Based on these results, it proposed a concept of cumulative flow velocity. Using curve-fitting equations, the limits of cumulative flow velocities as the monitoring time tends to infinity were then calculated as the actual flow velocities of the groundwater. The permeability coefficient of aquifer is calculated by using the fissure ratio of aquifer, hydraulic slope and flow velocity, and compared with the permeability coefficient obtained by pumping test. The results are as follows: (1) The variation coefficient of the instantaneous flow velocity measured at the same depth in the same well at different times is greater than that of the time average flow velocity and greater than that of the cumulative flow velocity. The variation coefficient of the actual velocity is the smallest, indicating that the risk of using the actual flow velocity is lower. (2) The variation coefficient of the flow rate monitored at different depths in the same well is mainly controlled by the properties of the aquifer. The more uniform water storage space in the aquifer, the smaller the variation coefficient. (3) The comparison between the permeability coefficient obtained by monitoring and the permeability coefficient obtained by pumping test shows that the flow of structural fissure water controlled by planar fissure is more surface flow, and the results are consistent. When the groundwater flow is controlled by pores and solution gaps, the flow channel is complicated, which is easy to produce turbulent flow, and the result consistency is poor. (4) According to different research accuracy requirements, different monitoring and calculation methods can be selected for different aquifers and groundwater types. Researches show that, the permeability coefficient calculated for the actual flow velocity in well DR01 is the same as that calculated for the pumping test. The aquifer characteristics reflected by the coefficient of variation of the actual flow velocity in the same aquifer are more realistic. The pumping test method obtains the comprehensive parameters of a certain aquifer, and this method can be used to monitor a certain fissure. In this paper, the new technology developed for monitoring, and the new algorithm established for data processing, can accurately obtain the flow velocity and direction of groundwater, using capsule hole mirror monitoring method. The key parameters of hydrogeology can be obtained by using one well, which can reduce the time and cost input and improve the work efficiency.

Abstract Background and aims The increasing prevalence of metabolic and cardiovascular diseases poses a significant challenge to global healthcare systems. Regular physical activity (PA) is recognized for its positive impact on cardiovascular risk factors. This study aimed to investigate the relationship between moderate-to-vigorous physical activity (MVPA), sedentary behavior (SB), and abdominal aortic calcification (AAC) using data from the National Health and Nutrition Examination Survey (NHANES). Methods The study used data from NHANES participants aged 40 and above during the 2013–2014 cycle. AAC scores were assessed using the Kauppila scoring system, and MVPA and SB were self-reported. Sociodemographic variables were considered, and multivariable linear regression models were used to analyze associations between MVPA, SB, and AAC scores. Subgroup analyses were conducted based on age, sex, BMI, hypertension, and diabetes. Results The study included 2843 participants. AAC prevalence was higher in older age groups, smokers, and those with diabetes or hypertension. Lower socioeconomic status was associated with higher AAC prevalence. Individuals engaged in any level of MVPA exhibited lower AAC rates compared to inactive individuals. Not engaging in occupational MVPA (β = 0.46, 95% confidence interval = 0.24‒0.67, p

Introduction Mild cognitive impairment (MCI) is an important intervenable stage for the prevention of dementia. Hypertension is associated with impaired cognition, and when combined with MCI, it may lead to a poor prognosis. Digital computerised cognitive training (CCT) has recently become a potential instrument for improving cognition, but evidence for its efficacy remains limited. This study aims to evaluate the efficacy of a digital adaptive CCT intervention in older patients with hypertension and MCI.Methods and analysis The multicentre, double-blinded, randomised, actively -controlled clinical trial will recruit 200 older (≥60 years) patients with hypertension and MCI from 11 hospitals across China. Participants will be randomly assigned in a 1:1 ratio to the intervention group (multidomain adaptative CCT) and active control group (non-adaptive cognitive training) for 12-week cognitive training for 30 min/day and 5 days/week. Those who have completed their 12-week training in the intervention group will be rerandomised into the continuation and discontinuation training groups. All participants will be followed up to 24 weeks. Neuropsychological assessments and structural and functional 7.0 T MRI will be obtained at baseline and at 12-week and 24-week follow-up. The primary outcome is the possible improvement of global cognitive function at 12 weeks, as measured by the Basic Cognitive Aptitude Tests. Secondary and exploratory endpoints include the major cognitive domain function improvement, self-efficacy, mental health, quality of life and MRI measurements of the brain.Ethics and dissemination The trial has been approved by the institutional review board of Beijing Anzhen Hospital and thereafter by all other participating centres. Trial findings will be disseminated in peer-reviewed journals and conference presentations.Trial registration number NCT05704270.

BackgroundRupture of abdominal aortic aneurysm (rAAA) is a fatal event in the elderly. Elevated blood pressure and weakening of vessel wall strength are major risk factors for this devastating event. This present study examined whether the expression profile of mechanosensitive genes correlates with the phenotype and outcome, thus, serving as a biomarker for AAA development.MethodsIn this study, we identified mechanosensitive genes involved in AAA development using general bioinformatics methods and machine learning with six human datasets publicly available from the GEO database. Differentially expressed mechanosensitive genes (DEMGs) in AAAs were identified by differential expression analysis. Molecular biological functions of genes were explored using functional clustering, Protein-protein interaction (PPI), and weighted gene co-expression network analysis (WGCNA). According to the datasets (GSE98278, GSE205071 and GSE165470), the changes of diameter and aortic wall strength of AAA induced by DEMGs were verified by consensus clustering analysis, machine learning models, and statistical analysis. In addition, a model for identifying AAA subtypes was built using machine learning methods.Results38 DEMGs clustered in pathways regulating 'Smooth muscle cell biology' and 'Cell or Tissue connectivity'. By analyzing the GSE205071 and GSE165470 datasets, DEMGs were found to respond to differences in aneurysm diameter and vessel wall strength. Thus, in the merged datasets, we formally created subgroups of AAAs and found differences in immune characteristics between the subgroups. Finally, a model that accurately predicts the AAA subtype that is more likely to rupture was successfully developed.ConclusionWe identified 38 DEMGs that may be involved in AAA. This gene cluster is involved in regulating the maximum vessel diameter, degree of immunoinflammatory infiltration, and strength of the local vessel wall in AAA. The prognostic model we developed can accurately identify the AAA subtypes that tend to rupture.

Objective To investigate the effect of miR-663b on the inflammatory response and apoptosis of nucleus pulposus cells (NPCs) induced by interleukin-1β (IL-1β) and its mechanism. Methods According to the different treatment me-thods, NPCs were divided into group A (no treatment), group B (induced by IL-1β), group C (IL-1β induction+miR-663b mimic transfection), and group D (IL-1β induction+miR-633b NC transfection). RT-qPCR was used to measure the expression levels of miR-663b, inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β], type Ⅱ collagen, and po-lysaccharide in NPCs; CCK-8 assay and TUNEL staining were used to observe the proliferation and apoptosis of NPCs; Western blotting was used to measure the protein expression level of interleukin-1 receptor 1 (IL1R1) in NPCs. TargetScan database was used to predict the potential binding sites between miR-663b and IL1R1. The 293T cells were divided into group E (transfected with IL1R1-wt plasmid+miR-663b mimic), group F (transfected with IL1R1-wt plasmid+miR-663b mimic), group G (transfected with IL1R1-mut plasmid+miR-663b mimic), and group H (transfected with IL1R1-mut plasmid+mimic NC), and the luciferase activity of NPCs was measured for each group. Results RT-qPCR results showed that compared with groups A, B, and D, group C had a significant increase in the relative expression level of miR-663b (t=9.41-22.93,P

Objective To evaluate the effect of icariin on sevoflurane-induced postoperative cognitive dysfunction (POCD),and to explore its potential mechanism. Methods The mice were divided into control group, model group(sevoflurane anesthesia + laparotomy were used to establish a mouse POCD model), icariin group, PI3K inhibitor group, icariin + inhibitor group, PI3K activator group, with 12 rats in each group. Conditional fear test and Y maze test were used to evaluate cognitive dysfunction in mice; ELISA method was used to detect the levels of serum TNF-α, IL-1β and BDNF; the hippocampal tissue was taken, Nissl staining was used to observe the changes of neuron morphology; TUNEL staining was used to detect neuronal apoptosis rate; the expression levels of M1 and M2 activated microglia and their markers were detected by immunofluorescence method; Western blot was used to detect the expression of TNF-α, IL-1β,IL-10, GSK-3β phosphorylated protein and Bcl-2. Results Compared with the control group, mice of model group showed cognitive impairment, severe hippocampal neuron impairment and apoptosis, the pro-inflammatory response mediated by M1 polarization of microglia in the hippocampus was more intensive than the anti-inflammatory response mediated by M2 polarization. The expression of PI3K/Akt-GSK-3β pathway and its mediated anti-inflammatory and anti-apoptotic proteins decreased (P＜0.05). Icariin and PI3K activator intervention promoted the PI3K/Akt-GSK-3β pathway and its anti-inflammatory and anti-apoptotic responses, and promote the anti-inflammatory response mediated by M2 polarization of hippocampal microglia, alleviated the impairment and apoptosis of hippocampal neurons, and improved cognitive function impairment of mice (P＜0.05). PI3K inhibitors could weaken the above-mentioned effects of icariin (P＜0.05). Conclusions The effect of icariin on improving the apoptosis of hippocampal neurons and cognitive impairment in POCD mice may be related to promoting the activation of PI3K/Akt pathway and enhancing the anti-inflammatory response mediated by M2 polarization of microglia.

Objective To compare the effect of flexible ureteroscopy lithotripsy and percutaneous nephrolithotripsy in treatment of renal calculi less than 3 cm. The effectiveness, reliability and the effect on inflammatory response of the two methods were compared. Methods From January 2015 to September 2021, 74 patients with renal calculi were collected and divided into FURS group and PCNL group with 35 in FURS group and 39 in PCNL group. The indexes before and after operation were compared. Results The statistically significant difference was found in operation time [(69.6±19.0)min vs(84.8±20.5)min], hospitalization days [(3.8±1.1)d vs (6.4±1.3)], intraoperative bleeding [(21.4±8.9)mL vs (75.4±48.6)mL,P＜0.01], pain VAS score [(1.0±0.9) vs (3.2±1.6),P＜0.01],freiburg patients satisfaction [(1.7±0.8) vs (2.2±1.1),P＜0.05] and complications (2.9% vs 17.9%,P＜0.05). Three days after operation, the COR[(209.3±20.9)ng/mL vs (226.4±38.8)ng/mL P＜0.05] and MDA [(6.9±0.6)nmol/mL vs (10.0±1.0)nmol/mL,P＜0.01] in the FURS group were lower than those in the PCNL group, while SOD [(70.6±8.3)NU/mL vs (61.3±7.8)NU/m) was higher than those in the PCNL group and the difference was statistically significant. The IL-6[(11.8±1.1)pg/mL vs (14.1±1.1)pg/mL,P＜0.001), IL-10 [(9.1±0.9)pg/mL vs (12.5±1.1)pg/mL,P＜0.001] and TNF-α[(1.7±0.1)ng/mL vs (2.3±0.1)ng/mL,P＜0.001]in the FURS group were significantly lower than those in the PCNL group three days after operation. Conclusions FURS is confirmed to be a safe and effective treatment for renal calculi less than 3 cm because of with low oxidative stress and inflammatory response.

Abstract. Background:. Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients. Methods:. From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA2DS2-VA score (excluding female sex from the CHA2DS2-VASc score). Results:. Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%–1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65–0.73), higher than that of CHA2DS2-VA score (0.66, 95% CI: 0.62–0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA2DS2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%–15.7%). Conclusion:. In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA2DS2-VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration:. www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

Abstract. Background. Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality, intensive care unit admission, and non-cardiovascular death. We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation (China-AF) Registry study. Methods. Clinical data of 8161 non-valvular atrial fibrillation (NVAF) patients who were antiarrhythmic drug (AAD)-naive before enrollment into the China-AF Registry, recruited between August 2011 and February 2017, were collected. The primary outcome was all-cause mortality. A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome. We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up. Results. Compared with 6167 patients of non-AAD group, 689 patients of the amiodarone group were younger (mean age 65.6 vs. 68.6 years), more frequently completed high school education, had fewer comorbidities such as chronic heart failure, prior bleeding, and stroke, and were more likely to be treated in tertiary hospitals while less hospitalization. The proportion of persistent AF was much lower among users of amiodarone, who were also less likely to be taking oral anticoagulants. The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality (2.44 vs. 3.91 per 100 person-years) over a mean follow-up duration of 300.6 ± 77.5 days. After adjusting for potential confounders, amiodarone use was not significantly associated with a lower risk of all-cause mortality (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42–1.49). Sub-group analysis revealed the consistent results. The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group. Conclusions. Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in “real-world” patients with NVAF.

Abstract. Background:. Interleukin-18 (IL18) gene polymorphisms are related to many inflammatory and autoimmune diseases. However, a correlation analysis between IL18 −607C/A and −137G/C gene polymorphisms and Takayasu arteritis (TA) is lacking. Methods:. This study enrolled 200 patients with TA as the case group and 334 region-, age-, and sex-matched healthy subjects as the control group. We genotyped alleles and genotypes at positions −607 and −137 of the IL18 gene and analyzed the distribution frequencies. Mann-Whitney U test, t test, Chi-squared test and Hardy-Weinberg equilibrium were performed. Results:. After adjusting for risk factors, the adjusted odds ratios and 95% confidence intervals at position −607C/A were 0.533, 0.391 to 0.880 (P = 0.010); 0.266, 0.586 to 1.002 (P = 0.051); and 0.122, 0.552 to 1.420 (P = 0.613) under the dominant, additive, and recessive models, respectively. For the −137G/C polymorphism, the adjusted odds ratios and 95% confidence intervals were 1.571, 1.068 to 2.311 (P = 0.022); 1.467, 1.086 to 1.980 (P = 0.012); and 1.815, 0.901 to 3.656 (P = 0.095) under the dominant, additive, and recessive models, respectively. Moreover, regardless of the model used, we found no statistical difference in distribution frequency between the active and quiescent states of TA for the −607C/A (P = 0.355, 0.631, and 0.705, respectively) and −137G/C polymorphisms (P = 0.205, 0.385, and 0.208, respectively). Conclusions:. The IL18 −607C/A gene polymorphism may decrease the risk of TA, and thus is a protective factor, whereas −137G/C may increase the risk of TA, and thus is a risk factor. However, neither polymorphism was related to activity (active vs. quiescent) of TA.

Objective To assess baseline characteristics and antithrombotic treatment (ATT) prescription patterns in patients enrolled in the third phase of the GLORIA-AF Registry Program, evaluate predictors of treatment prescription, and compare results with phase II. Methods GLORIA-AF is a large, global, prospective registry program, enrolling patients with newly diagnosed nonvalvular atrial fibrillation (AF) at risk of stroke. Patients receiving dabigatran were followed for two years in phase II, and all patients were followed for 3 years in phase III. Phase II started when dabigatran became available; phase III started when the characteristics of patients receiving dabigatran became roughly comparable with those receiving vitamin K antagonists (VKAs). Results Between 2014 and 2016, 21,241 patients were enrolled in phase III. In total, 82% of patients were prescribed oral anticoagulation ([OAC]; 59.5% novel/nonvitamin K oral anticoagulants [NOACs], 22.7% VKAs). A further 11% of patients were prescribed antiplatelets without OAC and 7% were prescribed no ATT. A high stroke risk was the main driver of OAC prescription. Factors associated with prescription of VKA over NOAC included type of site, region, physician specialty, and impaired kidney function. Conclusion Over the past few years, data from phase III of GLORIA-AF show that OACs have become the standard treatment option, with most newly diagnosed AF patients prescribed a NOAC. However, in some regions a remarkable proportion of patients remain undertreated. In comparison with phase II, more patients received NOACs in phase III while the prescription of VKA decreased. VKAs were preferred over NOACs in patients with impaired kidney function.

Summary: Background: Screening for atrial fibrillation before onset of symptoms and the subsequent initiation of oral anticoagulants could prevent stroke and death. The most cost-effective strategy to screen for atrial fibrillation in a population at high risk aged 65 years and older is unknown. Therefore, we aimed to investigate whether more frequent electrocardiography (ECG) recordings would significantly improve the detection of atrial fibrillation compared with annual ECG screenings. Methods: We did a randomised controlled trial that compared different screening frequencies of 30 s single-lead ECG (AliveCor Heart Monitor) in the detection of atrial fibrillation in Chinese residents (≥65 years) in five community health centres in Shanghai, China. Only participants without history of atrial fibrillation and without atrial fibrillation rhythm at baseline were eligible for inclusion in the trial. Random assignment was done with the use of a random number table and stratified for study site. Participants were randomly assigned in a 1:1 ratio to annual or quarterly screening groups. The quarterly screening group was further randomly assigned in a 3:1 ratio to subgroups of quarterly screening and quarterly screening plus (which involved ECG screening once per week for the first month of follow-up, then quarterly for the remainder of follow-up). The primary outcome was the detection rate of atrial fibrillation. The intention-to-treat analysis was done for all randomly assigned patients who had at least one ECG recording during follow-up. This trial was registered at ClinicalTrials.gov, NCT02990741, and terminated on Oct 31, 2020. Findings: Between April 17, 2017, and June 26, 2018, 8240 participants were randomly assigned to annual screening (n=4120), quarterly screening (n=3090), and quarterly screening plus (n=1030), with a mean number of ECG recordings of 1·6 (SD 0·5) for annual screening, 3·5 (1·5) for quarterly screening, and 5·2 (2·9) for quarterly screening plus during a median of 2·1 years follow-up (13 284 person-years). 73 incident cases of atrial fibrillation occurred: 26 in the annual screening group (4·1 per 1000 person-years) and 47 in the quarterly screening group (6·7 per 1000 person-years. Quarterly screening was associated with a significant increase in the detection rate of atrial fibrillation, compared with annual screening (hazard ratio [HR] 1·71; 95% CI 1·06–2·76; p=0·029). 40 incident cases were detected in quarterly screening (7·2 per 1000 person-years; HR compared to annual screening, 1·83; 95% CI 1·12–3·00; p=0·017) and seven in the quarterly screening plus group (4·8 per 1000 person-years; HR compared with annual screening, 1·24; 0·54–2·86; p=0·61). No significant difference was noted between quarterly screening and the quarterly screening plus group (HR of quarterly screening plus compared with quarterly screening, 0·68; 0·30–1·52; p=0·35). Interpretation: Quarterly 30 s single-lead ECG screening was associated with a significantly higher detection rate of incident atrial fibrillation compared with annual screening, but additional once per week screenings in the first month did not yield an added predictive value. Quarterly screening might be considered in a general population at a high risk of atrial fibrillation, such as those aged 65 years and older. Funding: Bayer Healthcare Company.

Objective Rapid, accurate identification of patients with acute myocardial infarction (AMI) at high risk of in-hospital major adverse cardiac events (MACE) is critical for risk stratification and prompt management. This study aimed to develop a simple, accessible tool for predicting in-hospital MACE in Chinese patients with AMI.Design Retrospective review of deidentified medical records.Setting 38 urban and rural hospitals across diverse economic and geographic areas in China (Beijing, Henan Province and Jilin Province).Participants 15 009 patients discharged from hospital with a diagnosis of AMI.Main outcome measure The primary outcome was MACE occurrence during index hospitalisation. A multivariate logistic regression model (China AMI Risk Model, CHARM) derived using patient data from Beijing (n=7329) and validated with data from Henan (n=4247) and Jilin (n=3433) was constructed to predict the primary outcome using variables of age, white cell count (WCC) and Killip class. C-statistics evaluated discrimination in the derivation and validation cohorts, with goodness-of-fit assessed using Hosmer-Lemeshow statistics.Results The CHARM model included age (OR: 1.06 per 1-year increment, 95% CI 1.05 to 1.07, p

BackgroundPatients with AF often have multimorbidity (the presence of ≥2 concomitant chronic conditions).ObjectiveTo describe baseline characteristics, patterns of antithrombotic therapy, and factors associated with oral anticoagulant (OAC) prescription in patients with AF and ≥2 concomitant, chronic, comorbid conditions.MethodsPhase III of the GLORIA-AF Registry enrolled consecutive patients from January 2014 through December 2016 with recently diagnosed AF and CHA2DS2-VASc score ≥1 to assess the safety and effectiveness of antithrombotic treatment.ResultsOf 21,241 eligible patients, 15,119 (71.2%) had ≥2 concomitant, chronic, comorbid conditions. The proportions of patients with multimorbidity receiving non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKA) were 60.2% and 23.6%, respectively. The proportion with paroxysmal AF was 57.0% in the NOAC group and 45.4% in the VKA group. Multivariable log-binomial regression analysis found the following factors were associated with no OAC prescription: pattern of AF (paroxysmal, persistent, or permanent), coronary artery disease, myocardial infarction, prior bleeding, smoking status, and region (Asia, North America, or Europe). Factors associated with OAC prescriptions were age, body mass index, renal function, hypertension, history of cerebral ischemic symptoms, and AF ablation.ConclusionMultimorbid AF patients prescribed NOACs have fewer comorbidities than those prescribed VKAs. Age, AF pattern, comorbidities, and renal function are associated with OAC prescription.

BackgroundAtrial fibrillation (AF) is underdiagnosed and especially undertreated in China. We aimed to investigate the prevalence of unknown and untreated AF in community residents (≥65 years old) and to determine whether an education intervention could improve oral anticoagulant (OAC) prescription.Methods and findingsWe performed a single-time point screening for AF with a handheld single-lead electrocardiography (ECG) in Chinese residents (≥65 years old) in 5 community health centers in Shanghai from April to September 2017. Disease education and advice on referral to specialist clinics for OAC treatment were provided to all patients with actionable AF (newly detected or undertreated known AF) at the time of screening, and education was reinforced at 1 month. Follow-up occurred at 12 months. In total, 4,531 participants were screened (response rate 94.7%, mean age 71.6 ± 6.3 years, 44% male). Overall AF prevalence was 4.0% (known AF 3.5% [n = 161], new AF 0.5% [n = 22]). The 183 patients with AF were older (p < 0.001), taller (p = 0.02), and more likely to be male (p = 0.01), and they had a higher prevalence of cardiovascular disease than those without AF (p < 0.001). In total, 85% (155/183) of patients were recommended for OAC treatment by the established guidelines (CHA2DS2-VASc ≥ 2 for men; ≥ 3 for women). OAC prescription rate for known AF was 20% (28/138), and actionable AF constituted 2.8% of all those screened. At the 12-month follow-up in 103 patients (81% complete), despite disease education and advice on specialist referral, only 17 attended specialist clinics, and 4 were prescribed OAC. Of those not attending specialist clinics, 71 chose instead to attend community health centers or secondary hospital clinics, with none prescribed OAC, and 15 had no review. Of the 17 patients with new AF and a class 1 recommendation for OAC, only 3 attended a specialist clinic, and none were prescribed OAC. Of the 28 AF patients taking OAC at baseline, OAC was no longer taken in 4. Ischemic stroke (n = 2) or death (n = 3) occurred in 5/126 (4%), with none receiving OAC. As screening was performed at a single time point, some paroxysmal AF cases may have been missed; thus, the rate of new AF may be underestimated.ConclusionsWe demonstrated a noticeable gap in AF detection and treatment in community-based elderly Chinese: actionable AF constituted a high proportion of those screened. Disease education and advice on specialist referral are insufficient to close the gap. Before more frequent or intensive screening for unknown AF could be recommended in China, greater efforts must be made to increase appropriate OAC therapy in known AF to prevent AF-related stroke.

Abstract. Background:. Alcohol consumption has been observed to be a contributing factor in liver damage. However, very few studies have tried to decipher the correlation between patients with liver disease and alcohol consumption. Therefore, this study was planned to determine the prevalence of alcohol consumption among patients with liver disease, and to evaluate the risk factors, liver diseases, and chronic medical conditions associated with alcohol drinking. Methods:. A cross-sectional study was conducted among patients with liver disease in 30 provinces, autonomous regions, and municipalities across China. All participants answered the questionnaire, which led to the calculation of Alcohol Use Disorders Inventory Test (AUDIT) score for each patient. Based on this score, low-risk drinkers, hazardous drinkers, and harmful drinkers were defined as having AUDIT score of

Glucagon-like peptide-1 (GLP-1) is easily degraded by dipeptidyl peptidase-4 (DPP-4) in the human body, limiting its therapeutic effect on type II diabetes. Therefore, improving GLP-1 receptor agonist (GLP-1RA) stability is a major obstacle for drug development. We analyzed human GLP-1, DPP-4, and GLP-1 receptor structures and designed three GLP-1RAs, which were introduced into fusion protein fragments and changed in the overall conformation. This modification effectively prevented GLP-1RAs from entering the DPP-4 active center without affecting GLP-1RAs’ ability to bind to GLP-1R, the new GLP-1RA hypoglycemic effect lasting for >24 h. Through molecular modeling, molecular dynamics calculation, and simulation, possible tertiary structure models of GLP-1RAs were obtained; molecular docking with DPP-4 and GLP-1R showed access to the fusion protein. The overall conformational change of GLP-1RAs prevented DPP-4 binding, without affecting GLP-1RAs’ affinity to GLP-1R. This study provides important drug design ideas for GLP-1RA development and a new example for application of structural biology-based protein design in drug development.

Abstract Background Medullary sponge kidney is a rare renal malformation, which usually manifests as nephrocalcinosis, renal tubular acidosis, and recurrent urinary tract infections. Medullary sponge kidney is often associated with renal developmental anomalies and tumors, and its exact pathogenesis is not yet clearly explained. Given the key role of the interaction of glial cell line-derived neurotrophic factor gene, GDNF, and the “rearranged during transfection” proto-oncogene, RET, in kidney and urinary tract development, variations in these genes are proposed to be candidates for medullary sponge kidney. Hyperparathyroidism is observed in a few patients with medullary sponge kidney, but the exact pathogenesis of this association is unknown. This case report highlights the coexistence of these two conditions associated with RET polymorphism, which contributes toward the understanding of the pathogenesis of medullary sponge kidney. Case presentation A 52-year-old Chinese woman with recurrent renal stones presented to our hospital. Subsequently she was diagnosed as having medullary sponge kidney and tertiary hyperparathyroidism and underwent parathyroidectomy. Genomic DNA was isolated from lymphocytes and the GDNF and RET genes were determined by Sanger sequencing. Two RET polymorphisms were found in our patient, one was nonsynonymous c.2071G>A (G691S; rs1799939) located in exon 11, the other was synonymous c.2712C>G. (p.S904S; rs1800863) located in exon 15. Conclusions We demonstrated a case of medullary sponge kidney combined with tertiary hyperparathyroidism, which contributes to further understanding of the pathogenesis of this disease. Besides, we also found RET G691S/S904S polymorphism in this patient, but additional studies are required to explore the role of the RET gene in medullary sponge kidney with hyperparathyroidism.

Abstract Background Primary bilateral macronodular adrenal hyperplasia is a rare cause of Cushing’s syndrome characterized by the presence of bilateral secretory adrenal nodules. Recent studies have shown that primary bilateral macronodular adrenal hyperplasia is caused by combined germline and somatic mutations of the ARMC5 gene. Exophthalmos is an underappreciated sign of Cushing’s syndrome. Case presentation A 52-year-old Chinese woman with progressively worsening bilateral proptosis presented to our hospital. Subsequently she was diagnosed as having primary bilateral macronodular adrenal hyperplasia and underwent bilateral laparoscopic adrenalectomy. Genomic deoxyribonucleic acid was isolated from lymphocytes as well as seven different adrenal nodules and the ARMC5 sequence was determined by Sanger sequencing. We identified one heterozygous ARMC5 germline mutation c.682C>T (p. Gln228*) and five heterozygous somatic mutations (c.310delG, c.347_357del11, c.267delC, c.283_289del7, and c.205-322del118) in five different adrenal nodules. All mutations are novel and were not found in any of the available online databases. To test whether the ARMC5 mutation induced messenger ribonucleic acid decay, real-time reverse transcriptase polymerase chain reaction was performed on patient and control adrenal tissue. We found that the adrenal cortex of our patient showed a low ARMC5 messenger ribonucleic acid expression compared with normal adrenal cortex, possibly as a result of nonsense-mediated messenger ribonucleic acid decay Conclusions We demonstrated extensive genetic diversity of ARMC5 in a patient with primary bilateral macronodular adrenal hyperplasia that started with exophthalmos, which contributes to further understanding of the pathogenesis of this disease. Early recognition of atypical symptoms and screening for ARMC5 mutation in patients with primary bilateral macronodular adrenal hyperplasia has important clinical implications for the diagnosis and genetic counseling.

Background: Unfractionated heparin (UFH), despite its limitations, has been used as the primary anticoagulant alternative during the percutaneous coronary intervention (PCI). Some studies indicated that intravenous enoxaparin could be an effective and safe option. Our team used enoxaparin alone at one time according to the guidelines (Class IIA) and found a little catheter thrombosis during PCI. We recommend a new anticoagulation strategy using enoxaparin in combination with UFH. Enoxaparin has a more predictable anticoagulant response with no need of repeatedly monitoring anticoagulation during PCI. This retrospective study aimed to evaluate the efficacy and safety of using enoxaparin in combination with UFH in PCI patients with complex coronary artery disease. Methods: Between January 2015 and April 2017, 600 PCI patients who received intravenous UFH at an initial dose of 3000 U plus intravenous enoxaparin at a dose of 0.75 mg/kg (observation group) and 600 PCI patients who received UFH at a dose of 100 U/kg (control group) were consecutively included in this retrospective study. The endpoints were postoperative 48-h thrombolysis in myocardial infarction (TIMI) bleeding and transfusion and 30-day and 1-year major adverse cardio-cerebrovascular events (MACCE). Results: Baseline clinical, angiographic, and procedural characteristics were similar between groups, except there was less stent implantation per patient in the observation group (2.13 vs. 2.25 in the control group, P = 0.002). TIMI bleeding (3.3% vs. 4.7%) showed no significant difference between the observation group and control group. During the 30-day follow-up, the rate of MACCE was 0.9% in the observation group and 1.5% in the control group. There was no significant difference in the rates of MACCE, death, myocardial infarction, target vessel revascularization, cerebrovascular event, and angina within 30 days and 1 year after PCI between groups as well as in the subgroup analysis of transfemoral approach. Conclusions: UFH with sequential enoxaparin has similar anticoagulant effect and safety as UFH in PCI of complex coronary artery disease.

Background: A single drilled tunnel from the lateral mastoid cortex to the cochlea via the facial recess is essential for minimally invasive cochlear implant surgery. This study aimed to explore the safety profile of this kind of new image-guided and bi-planar device-assisted surgery procedure in vitro. Methods: Image-guided minimally invasive cochlear implantations were performed on eight cadaveric temporal bone specimens. The main procedures were: (1) temporal bone specimens were prepared for surgery and fiducial markers were registered. (2) computed tomography (CT) scans were performed for future reference. (3) CT scan images were processed and drill path was planned to minimize cochlear damage. (4) bi-planar device-assisted drilling was performed on the specimens using the registration. (5) surgical safety was evaluated by calculating the deviation between the drill and the planned paths, and by measuring the closest distance between the drilled path and critical anatomic structures. Results: Eight cases were operated successfully to the basal turn of the cochlear with intact facial nerves (FNs). The deviations from target points and entrance points were 0.86 mm (0.68-1.00 mm) and 0.44 mm (0.30-0.96 mm), respectively. The angular error between the planned and the drilled trajectory was 1.74° (1.26-2.41°). The mean distance from the edge of the drilled path to the FN and to the external canal was 0.60 mm (0.35-0.83 mm) and 1.60 mm (1.30-2.05 mm), respectively. In five specimens, the chorda tympani nerves were well preserved. In all cases, no injury happened to auditory ossicles. Conclusions: This exploratory study demonstrated the safety of the newly developed image-guided minimally invasive cochlear implantation assisted by the bi-planar device and established the operational procedures. Further, more in vitro experiments are needed to improve the system operation and its safety.

Background: Warfarin is the most common oral anticoagulant to decrease the stroke risk associated with atrial fibrillation (AF). There are very few prospective studies that have explored whether warfarin has an association with damage on renal function in Chinese patients with nonvalvular AF (NVAF). The aim of this study was to evaluate the effects of warfarin on renal function and study the factors associated with kidney dysfunction in Chinese adult NVAF patients without dialysis therapy. Methods: From January 2011 to December 2013, a total of 951 NVAF patients from 18 hospitals were enrolled. The estimated glomerular filtration rate (eGFR) was calculated from baseline and follow-up serum creatinine levels. Kaplan–Meier survival curves compared the survival of a ≥25% decline in eGFR (hereafter, endpoint), while Cox models estimated hazard ratios (HR s) and 95% confidence intervals for this event after adjustment for age, gender, and selected potential risk factors for renal dysfunction. Cox regression analysis of the various clinical potential variables was performed to identify the predictors of a ≥25% decline in eGFR. Results: After a 58-month follow-up, 951 NVAF patients were divided by observation into warfarin (n = 655) and no anticoagulation groups (n = 296) and 120 (12.6%) patients experienced renal endpoint. Kaplan–Meier survival curves showed that the survival period was not different in the two groups (χ2 = 0.178, log-rank P= 0.67), but patients with systolic blood pressure (SBP)

The polyphagous agromyzid fly, Liriomyza trifolii, is a significant and important insect pest of ornamental and vegetable crops worldwide. The adaptation of insects to different environments is facilitated by heat shock proteins (HSPs), which play an important role in acclimation to thermal stress. In this study, we cloned and characterized five HSP-encoding genes of L. trifolii (Lthsp20, Lthsp40, Lthsp60, Lthsp70, and Lthsp90) and monitored their expression under different thermal stresses using real-time quantitative PCR. Pupae of L. trifolii were exposed to 19 different temperatures ranging from -20 to 45°C. The results revealed that Lthsp20, Lthsp40, Lthsp70 and Lthsp90 were significantly upregulated in response to both heat and cold stress, while Lthsp60 was induced only by heat temperatures. The temperatures of the onset (Ton) and maximal (Tmax) expression of the five Lthsps were also determined and compared with published Ton and Tmax values of homologous genes in L. sativae and L. huidobrensis. Although L. trifolii occurs primarily in southern China, it has cold tolerance comparable with the other two Liriomyza species. Based on the heat shock proteins expression patterns, L. trifolii has the capacity to tolerate extreme temperatures and the potential to disseminate to northern regions of China.