Permanent pacemaker reduction using temporary-permanent pacemaker as a 1-month bridge after transcatheter aortic valve replacement: a prospective, multicentre, single-arm, observational study.

Background: The permanent pacemaker (PPM) implantation and pacemaker dependency rates after transcatheter aortic valve replacement (TAVR) are highly variable as some of the conduction disturbances are reversible. It remains poorly investigated how to optimise temporary pacing in these patients. This study aimed to explore the potential reduction in the PPM implantation rate using temporary-permanent pacemaker (TPPM) as a 1-month bridge. Methods: This is a prospective, multicentre, single-arm, observational study. Consecutive patients undergoing TAVR from March 1, 2022 to March 1, 2023 in 13 tertiary hospitals in China were screened. Patients who developed high-degree atrioventricular block, complete heart block, or first-degree atrioventricular block plus new onset left bundle branch block during the TAVR procedure or within 1 month after TAVR were included to receive TPPM. Patients with pre-existing PPM implantation or indications for PPM implantation before the TAVR procedure were excluded. Patients with TPPM were monitored to determine whether the conduction disturbances persisted or recovered. The primary endpoint was the rate of freedom from indications for PPM implantation 1 month after TAVR. This study is registered with ChiCTR, ChiCTR2200057931. Findings: Of 688 patients who have undergone TAVR, 71 developed conduction disturbance and met the inclusion criteria, 1 patient withdrew due to noncompliance, 70 patients received TPPM and completed follow-up. There were 41 (58.6%) men and 29 (41.4%) women in the study, with a mean age of 74.3 ± 7.3 years. At 1 month follow-up, 75.7% (53/70) of the patients with TPPM did not require PPM implantation. For 688 patients who have undergone TAVR, the rate of PPM implantation at 1 month was 2.47% (17/688, 95% CI 1.55%-3.92%), representing a significant reduction in self-comparison with the rate at 48 h after TPPM (2.47% vs. 8.28% [95% CI 6.45%-10.58%], P < 0.0001). Similar results were obtained in the subgroup analysis of patients with HAVB/CHB. Multivariate analysis revealed the baseline PR interval, difference between the membranous septum length and implantation depth, and timing of postprocedural conduction disturbance occurrence were independent predictors of freedom from indications for PPM implantation at 1 month after TAVR. Interpretation: Using TPPM as a 1-month bridge allows for a buffer period to distinguish whether conduction disturbances are reversible or persistent, resulting in a significant reduction in the PPM implantation rate after TAVR when compared with the current strategy. However, this is an observational study, the results need to be confirmed in a randomized trial. Funding: Beijing Science and Technology Plan 2022 from Beijing Municipal Science & Technology Commission.

Plasma metabolomics reveals the shared and distinct metabolic disturbances associated with cardiovascular events in coronary artery disease.

Risk prediction for subsequent cardiovascular events remains an unmet clinical issue in patients with coronary artery disease. We aimed to investigate prognostic metabolic biomarkers by considering both shared and distinct metabolic disturbance associated with the composite and individual cardiovascular events. Here, we conducted an untargeted metabolomics analysis for 333 incident cardiovascular events and 333 matched controls. The cardiovascular events were designated as cardiovascular death, myocardial infarction/stroke and heart failure. A total of 23 shared differential metabolites were associated with the composite of cardiovascular events. The majority were middle and long chain acylcarnitines. Distinct metabolic patterns for individual events were revealed, and glycerophospholipids alteration was specific to heart failure. Notably, the addition of metabolites to clinical markers significantly improved heart failure risk prediction. This study highlights the potential significance of plasma metabolites on tailed risk assessment of cardiovascular events, and strengthens the understanding of the heterogenic mechanisms across different events.

Estimation of invasive coronary perfusion pressure using electrocardiogram and Photoplethysmography in a porcine model of cardiac arrest.

BACKGROUND: Coronary perfusion pressure (CPP) indicates spontaneous return of circulation and is recommended for high-quality cardiopulmonary resuscitation (CPR). This study aimed to investigate a method for non-invasive estimation of CPP using electrocardiography (ECG) and photoplethysmography (PPG) during CPR. METHODS: Nine pigs were used in this study. ECG, PPG, invasive arterial blood pressure (ABP), and right atrial pressure (RAP) signals were simultaneously recorded. The CPPs were estimated using three datasets: (a) ECG, (b) PPG, and (c) ECG and PPG, and were compared with invasively measured CPPs. Four machine-learning algorithms, namely support vector regression, random forest (RF), K-nearest neighbor, and gradient-boosted regression tree, were used for estimation of CPP. RESULTS: The RF model with a combined ECG and PPG dataset achieved better estimation of CPP than the other algorithms. Specifically, the mean absolute error was 4.49 mmHg, the root mean square error was 6.15 mm Hg, and the adjusted R2 was 0.75. A strong correlation was found between the non-invasive estimation and invasive measurement of CPP (r = 0.88), which supported our hypothesis that machine-learning-based analysis of ECG and PPG parameters can provide a non-invasive estimation of CPP for CPR. CONCLUSIONS: This study proposes a novel estimation of CPP using ECG and PPG with machine-learning-based algorithms. Non-invasively estimated CPP showed a high correlation with invasively measured CPP and may serve as an easy-to-use physiological indicator for high-quality CPR treatment.

Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis.

Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products (AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.

Alloreactive T cells temporarily increased in peripheral blood of patients before liver allograft rejection.

T cells are key mediators of alloresponse during liver transplantation (LTx). However, the dynamics of donor-reactive T cell clones in peripheral blood during a clinical T-cell-mediated rejection (TCMR) episode remain unknown. Here, we collected serial peripheral blood mononuclear cells (PBMCs) samples spanning from pre-LTx to one-year post-LTx and available biopsies during the TCMR episodes from 26 rejecting patients, and serial PBMC samples were collected from 96 non-rejectors. Immunophenotypic and repertoire analyses were integrated on T cells from rejectors and longitudinally compared them to non-rejected patients. Donor-reactive T cell clone was identified and tracked by cross-matching with mappable donor-reactive TCR repertoire of each donor-recipient pair in 9 rejectors and 5 non-rejectors. Before transplantation, the naive T cell percentage and TCR repertoire diversity of rejectors was comparable to healthy control, it was reduced in non-rejectors. After transplantation, the naïve T cell percentages decreased and TCR repertoires were skewed in rejectors, the phenomenon was not observed in non-rejectors. Alloreactive clones increased in proportion in peripheral blood of rejectors before TCMR for weeks. The increase was accompanied by the naïve T cell decline and memory T cell increase and acquired an activated phenotype. Intragraft alloreactive clone tracking in pre- and post-LTx PBMC samples revealed that the pre-transplant naïve T cells were significant contributors to the donor-reactive clones, and they temporarily increased in proportion and subsequently reduced in blood at the beginning of TCMR. Together, our findings offer an insight into the dynamic and origin of alloreactive T cells in clinical LTx TCMR cases, and may facilitate disease prediction and management.

Long-term PM2.5 exposure associated with severity of angina pectoris and related health status in patients admitted with acute coronary syndrome: Modification effect of genetic susceptibility and disease history.

Long-term particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) exposure has been associated with the occurrence of acute coronary syndrome (ACS). However, the impact of PM2.5 exposure and its components on the severity of angina pectoris and disease-related health status in patients hospitalized for ACS is understudied. To assess the association between long-term exposure to PM2.5 components and the angina pectoris severity in ACS patients, as well as the modification effects of genetic factors and disease history in north China. During 2017-2019, 6729 ACS patients were collected in Shandong Province and Beijing, with their angina pectoris severity evaluated using Seattle Angina Questionnaire (SAQ). The 0-3 years' average concentrations of PM2.5 and its five major components were assigned to each patient's residential address. Linear mixed-effects model, weighted quantile regression, and quantile g-computation were used to estimate the effects of both single and joint associations between PM2.5 components and SAQ scores. The interactive effect was estimated by polygenic risk scores and disease history. For each interquartile range increase in PM2.5, the overall SAQ score changed by -3.71% (95%CI: -4.54% to -2.88%), with score of angina stability more affected than angina frequency and other dimensions of angina pectoris severity. Sulfate and ammonium were major contributors to the effect of PM2.5 exposure. Significant modification effect was only observed for disease history, especially for the dimension of physical limitation. Among a series of pre-existing diseases, patients with a family history of coronary artery disease, previous percutaneous coronary intervention or coronary artery bypass grafting, and stroke were more susceptible to PM2.5 exposure than others. Greater exposure to PM2.5 is associated with more serious angina pectoris and worse disease-related health status in ACS patients. Public health and clinical priority should be given to cutting down key effective components and protecting highly vulnerable individuals.

A vision chip with complementary pathways for open-world sensing.

Image sensors face substantial challenges when dealing with dynamic, diverse and unpredictable scenes in open-world applications. However, the development of image sensors towards high speed, high resolution, large dynamic range and high precision is limited by power and bandwidth. Here we present a complementary sensing paradigm inspired by the human visual system that involves parsing visual information into primitive-based representations and assembling these primitives to form two complementary vision pathways: a cognition-oriented pathway for accurate cognition and an action-oriented pathway for rapid response. To realize this paradigm, a vision chip called Tianmouc is developed, incorporating a hybrid pixel array and a parallel-and-heterogeneous readout architecture. Leveraging the characteristics of the complementary vision pathway, Tianmouc achieves high-speed sensing of up to 10,000 fps, a dynamic range of 130 dB and an advanced figure of merit in terms of spatial resolution, speed and dynamic range. Furthermore, it adaptively reduces bandwidth by 90%. We demonstrate the integration of a Tianmouc chip into an autonomous driving system, showcasing its abilities to enable accurate, fast and robust perception, even in challenging corner cases on open roads. The primitive-based complementary sensing paradigm helps in overcoming fundamental limitations in developing vision systems for diverse open-world applications.

Formyl peptide receptor 1 mitigates colon inflammation and maintains mucosal homeostasis through the inhibition of CREB-C/EBPß-S100a8 signaling.

Excessive inflammatory responses are the main characteristic of ulcerative colitis (UC). Activation of formyl peptide receptor 1 (FPR1) has been found to promote the proliferation and migration of epithelial cells, but its role and therapeutic potential in UC remain unclear. This study observed an increased expression of FPR1 in a mouse model of colitis. Interestingly, FPR1 deficiency exacerbated UC and increased the secretion of the proinflammatory mediator from immune cells (e.g. macrophages), S100a8, a member of the damage-associated molecular patterns. Notably, the administration of the FPR agonist Cmpd43 ameliorated colon injury in a preclinical mice model of UC, likely via inhibiting phosphorylation of cyclic adenosine monophosphate-response element-binding protein and expression of CCAAT/enhancer-binding protein ß, which in turn suppressed the secretion of S100a8. In conclusion, these findings discovered a novel role of FPR1 in the development of colitis and will facilitate the development of FPR1-based pharmacotherapy to treat UC.

[Effect of Intensive Insulin Therapy on Prognosis in Patients With Acute Myocardial Infarction].

Objective To evaluate the clinical efficacy and safety of intensive insulin therapy in the patients with acute myocardial infarction and provide guidance for improving the prognosis. Methods The articles involving the randomized controlled trials(RCT)focusing on the effects of intensive versus conventional insulin therapy on the clinical outcomes of the patients with acute myocardial infarction were retrieved from Cochrane,Embase,PubMed,CNKI,Wanfang Data,VIP,and CBM with the time interval from inception to October 2022.The data of each RCT were extracted and used for meta-analysis in RevMan5.4. Results A total of 8 articles were included in this study,involving 726 patients(372 in the intensive insulin group and 354 in the normal insulin group).The meta-analysis results showed that the intensive insulin group had lower incidence of major cardiovascular adverse events (RR=0.53, 95%CI=0.44-0.64, P<0.001), lower all-cause mortality (RR=0.51, 95%CI=0.33-0.78, P=0.002),lower high-sensitivity C-reactive protein level on day 7(WMD=-2.00,95%CI=-2.17- -1.83,P<0.001),higher left ventricular ejection fraction on day 30 (WMD=3.94, 95%CI=2.45-5.43,P<0.001), and higher incidence of hypoglycemia events (RR=2.96, 95%CI=1.12-7.83,P=0.030) than the normal insulin group.There was no significant difference between the two groups in terms of no-reflow event after percutaneous coronary intervention(RR=0.39,95%CI=0.14-1.13,P=0.080). Conclusion Intensive insulin therapy might be associated with more clinical benefits in the patients with acute myocardial infarction,while the conclusion remains to be confirmed by more studies.

Characterization of Fusarium solani Associated with Tobacco (Nicotiana tabacum) Root Rot in Henan, China.

The aim of this study was to characterize the Fusarium solani species complex (FSSC) population obtained from tobacco roots with root rot symptoms by morphological characteristics, molecular tests, and assessment of pathogenicity. Cultures isolated from roots were white to cream with sparse mycelium on potato dextrose agar, with colony growth of 21.5 ± 0.5 to 29.5 ± 0.5 mm after 3 days. Sporodochia were cream on carnation leaf agar (CLA) and Spezieller Nährstoffarmer agar (SNA), and macroconidia formed in sporodochia were 3 to 6 septate and straight to slightly curved, with wide central cells, a slightly short blunt apical cell, and a straight to almost cylindrical basal cell with a distinct foot shape, ranging in size from 20.92 to 64.37 × 3.91 to 6.57 µm. Microconidia formed on CLA were reniform and fusiform, with 0 or 1 to occasionally 2 septa, that formed on long monophialidic conidiogenous cells, with a size range of 5.99 to 32.32 × 1.76 to 5.84 µm. Globose to oval chlamydospores were smooth- to rough-walled, 6.5 to 13.3 ± 0.37 µm in diameter, and terminal or intercalary and occurred singly, in pairs, or occasionally in short chains on SNA. Molecular tests consisted of sequencing and phylogenetic analysis of the translation elongation factor-1 alpha (EF-1α), RNA polymerase II largest subunit, and second largest subunit regions. All the obtained sequences revealed 98.14 to 100% identity to F. solani in both Fusarium ID and Fusarium MLST databases. Phylogenetic trees of the EF-1α gene and concatenated three-locus data showed that isolates from tobacco in Henan grouped in the proposed group 5, which is nested within FSSC clade 3 (FSSC 5). Twenty-seven of the 28 isolates caused root rot in artificially inoculated tobacco seedlings, with a disease severity index ranging from 15.00 ± 1.67 to 91.11 ± 2.22. Cross-pathogenicity tests showed that three representative isolates were virulent to six species of Solanaceae and two species of Poaceae, with disease severity indexes ranging from 6.12 ± 0.56 to 84.44 ± 0.00, indicating that these isolates have a wide host range. The results may inform the control of tobacco root rot through improved crop rotations.

Study of Hydration Repulsion of Zwitterionic Polymer Brushes Resistant to Protein Adhesion through Molecular Simulations.

The fabrication of antifouling zwitterionic polymer brushes represents a leading approach to mitigate nonspecific adhesion on the surfaces of medical devices. This investigation seeks to elucidate the correlation between the material composition and structural attributes of these polymer brushes in preventing protein adhesion. To achieve this goal, we modeled three different zwitterionic brushes, namely, carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and (2-(methacryloyloxy)ethyl)-phosphorylcholine (MPC). The simulations revealed that elevating the grafting density enhances the structural stability, hydration strength, and resistance to protein adhesion exhibited by the polymer brushes. PCBMA manifests a more robust hydration layer, while PMPC demonstrates the slightest interaction with proteins. In a comprehensive evaluation, PSBMA polymer brushes emerged as the best choice with superior stability, enhanced protein repulsion, and minimally induced protein deformation, resulting in effective resistance to nonspecific adhesion. The high-density SBMA polymer brushes significantly reduce the level of protein adhesion in AFM testing. In addition, we have pioneered the quantitative characterization of hydration repulsion in polymer brushes by analyzing the hydration repulsion characteristics at different materials and graft densities. In summary, our study provides a nuanced understanding of the material and structural determinants influencing the capacity of zwitterionic polymer brushes to thwart protein adhesion. Additionally, it presents a quantitative elucidation of hydration repulsion, contributing to the advancement and application of antifouling polymer brushes.

A national survey on current state and development needs of clinical and academic emergency medicine in China.

BACKGROUND: To characterize the current state of emergency medicine (EM) and the requirements for advancing EM clinical practice, education and research in China. METHODS: An anonymous electronic survey was conducted by Chinese Society of Emergency Medicine during September to October 2021. The survey contained 30 questions divided into 2 sections: the current state of EM development and the requirements for EM growth. RESULTS: 722 hospitals were included, of 487 were Level III and 235 were Level II hospitals. We found that after 40 years of development, EM had established a mature disciplinary system and refined sub-specialties including critical care, cardiopulmonary resuscitation, toxicology, disaster and emergency rescue. In Level III hospitals, 70.8% of EDs were standardized training centers for EM residents, but master's degree program, Doctor Degree program and post-doctoral degree program was approved in only 37.8%, 8.4% and 2.9% of EDs respectively and postgraduate curriculum was available in 1/4 of EDs. Only 8% have national or provincial key laboratories. In addition to advance clinical practice, there was also a high demand to improve teaching and research capacities, mainly focusing on literature review, research design and delivery, paper writing, residency training. CONCLUSIONS: EM has built a mature discipline system and refined sub-specialties in China. Teaching and research developed parallel with clinical practice. However, there was still a lack of EM master's and doctoral programs and research capacities need to be improved. More outstanding clinical and academic training should be provided to promote the rapid growth of EM in China.

Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS.

Acetaldehyde dehydrogenase 2 (ALDH2) mutations are commonly found in a subgroup of the Asian population. However, the role of ALDH2 in septic acute respiratory distress syndrome (ARDS) remains unknown. Here, we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS. Intriguingly, ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA (cfDNA) and myeloperoxidase (MPO)-DNA than ALDH2WT-ARDS patients. To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS, we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice. In clinically relevant mouse sepsis models, Aldh2-/- mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis, a specific process that releases neutrophil extracellular traps (NETs) from neutrophils. Furthermore, we discovered that NETosis strongly promoted endothelial destruction, accelerated vascular leakage, and exacerbated septic ARDS. At the molecular level, ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4 (PAD4) to inhibit NETosis, which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP. Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis. Together, our data reveal a novel ALDH2-based protective mechanism against septic ARDS, and the activation of ALDH2 may be an effective treatment strategy for sepsis.

The development history, current state, challenges, and future directions of the BASIC-OHCA registry in China: A narrative review.

Out-of-hospital cardiac arrest is a major public health problem worldwide due to its high burden and poor outcomes. Despite progress in treatment, patient outcomes remain unsatisfactory, particularly in low-resource settings. The establishment of a registry is the first step towards gaining a comprehensive understanding of prevailing local conditions and identifying potential opportunities for improving patient survival. Here, we provide a narrative review of the BASeline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA), the first national OHCA registry in China, to introduce its development history, current state, challenges and future directions. We aim to enhance cross-cultural understanding by providing insights from China, while also serving as a reference for the implementation of large-scale registries in low-resource settings.

Extracorporeal Versus Conventional Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest: A Propensity Score Matching Cohort Study.

OBJECTIVE: Comparing the effects of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) on outcomes in patients with in-hospital cardiac arrest (IHCA) in China. The benefits of ECPR over CCPR in patients with IHCA remain controversial. DESIGN: This article analyzed data from the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA) study, which consecutively enrolled patients with IHCA from July 1, 2019, to December 31, 2020. Patients who received ECPR were selected as the case group and matched with patients who received CCPR as the control group by propensity score at a ratio of 1:4. A parallel questionnaire survey of participating hospitals was conducted, to collect data on ECPR cases from January 1, 2021 to November 30, 2021. The primary outcome was survival to discharge or 30-day survival. SETTING: We included 39 hospitals across 31 provinces in China. PATIENTS: Patients receiving cardiopulmonary resuscitation and without contraindications to ECPR were selected from the BASIC-IHCA database. Patients older than 75 years, not witnessed, or with cardiopulmonary resuscitation duration less than 10 min were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 4853 patients met the inclusion criteria before matching, with 34 undergoing ECPR (median age, 56.5 yr; 67.65% male) and 4819 underwent CCPR (median age, 59 yr; 64.52% male). There were 132 patients receiving CCPR and 33 patients receiving ECPR who were eventually matched. The ECPR group had significantly higher survival rates at discharge or 30-day survival (21.21% vs. 7.58%, p = 0.048). The ECPR group had significantly lower mortality rates (hazard ratio 0.57; 95% CI, 0.38-0.91) than the CCPR group at discharge or 30 days. Besides the BASIC-IHCA study, the volume of ECPR implementations and the survival rate of patients with ECPR (29.4% vs. 10.4%. p = 0.004) in participating hospitals significantly improved. CONCLUSIONS: ECPR may be beneficial compared with CCPR for patient survival after IHCA and should be considered for eligible patients with IHCA.

High-density zwitterionic polymer brushes exhibit robust lubrication properties and high antithrombotic efficacy in blood-contacting medical devices.

High-performance catheters are essential for interventional surgeries, requiring reliable anti-adhesive and lubricated surfaces. This article develops a strategy for constructing high-density sulfobetaine zwitterionic polymer brushes on the surface of catheters, utilizing dopamine and sodium alginate as the primary intermediate layers, where dopamine provides mussel-protein-like adhesion to anchor the polymer brushes to the catheter surface. Hydroxyl-rich sodium alginate increases the number of grafting sites and improves the grafting mass by more than 4 times. The developed high-density zwitterionic polymer brushes achieve long-lasting and effective lubricity (µ<0.0078) and are implanted in rabbits for four hours without bio-adhesion and thrombosis in the absence of anticoagulants such as heparin. Experiments and molecular dynamics simulations demonstrate that graft mass plays a decisive role in the lubricity and anti-adhesion of polymer brushes, and it is proposed to predict the anti-adhesion of polymer brushes by their lubricity to avoid costly and time-consuming bioassays during the development of amphoteric polymer brushes. A quantitative influence of hydration in the anti-adhesion properties of amphiphilic polymer brushes is also revealed. Thus, this study provides a new approach to safe, long-lasting lubrication and anticoagulant surface modification for medical devices in contact with blood. STATEMENT OF SIGNIFICANCE: High friction and bioadhesion on medical device surfaces can pose a significant risk to patients. In response, we have developed a safer, simpler, and more application-specific surface modification strategy that addresses both the lubrication and anti-bioadhesion needs of medical device surfaces. We used dopamine and sodium alginate as intermediate layers to drastically increase the grafting density of the zwitterionic brushes and enabled the modified surfaces to have an extremely low coefficient of friction (µ = 0.0078) and to remain non-bioadhesive for 4 hours in vivo. Furthermore, we used molecular dynamics simulations to gain insight into the mechanisms behind the superior anti-adhesion properties of the high-density polymer brushes. Our work contributes to the development and application of surface-modified coatings.

Distribution and prognostic value of high-sensitivity cardiac troponin T and I across glycemic status: a population-based study.

BACKGROUND: Whether distributions and prognostic values of high-sensitivity cardiac troponin (hs-cTn) T and I are different across normoglycemic, prediabetic, and diabetic populations is unknown. METHODS: 10127 adult participants from the National Health and Nutrition Examination Survey 1999-2004 with determined glycemic status and measurement of at least one of hs-cTn assays were included, from whom healthy participants and presumably healthy diabetic and prediabetic participants were selected to investigate pure impacts of glycemic status on distributions of hs-cTn. The nonparametric method and bootstrapping were used to derive the 99th upper reference limits of hs-cTn and 95% CI. Participants with available follow-up and hs-cTn concentrations of all 4 assays were included in prognostic analyses. Associations of hs-cTn with all-cause and cardiac-specific mortality were modeled by Cox proportional hazard regression under the complex survey design. The incremental value of hs-cTn to an established risk score in predicting cardiac-specific mortality was assessed by the 10-year area under time-dependent receiver operating characteristic curve (AUC) using the Fine-Grey competing risk model. RESULTS: Among 9714 participants included in prognostic analyses, 5946 (61.2%) were normoglycemic, 2172 (22.4%) prediabetic, and 1596 (16.4%) diabetic. Hyperglycemic populations were older than the normoglycemic population but sex and race/ethnicity were similar. During the median follow-up of 16.8 years, hs-cTnT and hs-cTnI were independently associated with all-cause and cardiac-specific mortality across glycemic status. In the diabetic population, adjusted hazard ratios per 1-standard deviation increase of log-transformed hs-cTnT and hs-cTnI (Abbott) concentrations were 1.77 (95% CI 1.48-2.12; P < .001) and 1.83 (95% CI 1.33-2.53; P < .001), respectively, regarding cardiac-specific mortality. In the diabetic but not the normoglycemic population, adding either hs-cTnT (difference in AUC: 0.062; 95% CI 0.038-0.086; P < 0.001) or hs-cTnI (Abbott) (difference in AUC: 0.071; 95% CI 0.046-0.097; P < 0.001) would significantly increase the discriminative ability of the risk score; AUC of the score combined with hs-cTnT would be further improved by incorporating hs-cTnI (0.018; 95%CI 0.006-0.029; P = 0.002). The 99th percentile of hs-cTnT of the presumably healthy diabetic population was higher than the healthy population and had no overlap in 95% CIs, however, for hs-cTnI 99th percentiles of the two populations were very close and 95% CIs extensively overlapped. CONCLUSIONS: Hs-cTnT and hs-cTnI demonstrated consistent prognostic associations across glycemic status but incremental predictive values in hyperglycemic populations only. The susceptibility of hs-cTnT 99th percentiles to diabetes plus the additive value of hs-cTnI to hs-cTnT in diabetic cardiovascular risk stratification suggested hs-cTnI and hs-cTnT may be differentially associated with glycemic status, but further research is needed to illustrate the interaction between hyperglycemia and hs-cTn.

Carbonylation of Runx2 at K176 by 4-Hydroxynonenal Accelerates Vascular Calcification.

BACKGROUND: Vascular calcification, which is characterized by calcium deposition in arterial walls and the osteochondrogenic differentiation of vascular smooth muscle cells, is an actively regulated process that involves complex mechanisms. Vascular calcification is associated with increased cardiovascular adverse events. The role of 4-hydroxynonenal (4-HNE), which is the most abundant stable product of lipid peroxidation, in vascular calcification has been poorly investigated. METHODS: Serum was collected from patients with chronic kidney disease and controls, and the levels of 4-HNE and 8-iso-prostaglandin F2α were measured. Sections of coronary atherosclerotic plaques from donors were immunostained to analyze calcium deposition and 4-HNE. A total of 658 patients with coronary artery disease who received coronary computed tomography angiography were recruited to analyze the relationship between coronary calcification and the rs671 mutation in aldehyde dehydrogenase 2 (ALDH2). ALDH2 knockout (ALDH2-/-) mice, smooth muscle cell-specific ALDH2 knockout mice, ALDH2 transgenic mice, and their controls were used to establish vascular calcification models. Primary mouse aortic smooth muscle cells and human aortic smooth muscle cells were exposed to medium containing ß-glycerophosphate and CaCl2 to investigate cell calcification and the underlying molecular mechanisms. RESULTS: Elevated 4-HNE levels were observed in the serum of patients with chronic kidney disease and model mice and were detected in calcified artery sections by immunostaining. ALDH2 knockout or smooth muscle cell-specific ALDH2 knockout accelerated the development of vascular calcification in model mice, whereas overexpression or activation prevented mouse vascular calcification and the osteochondrogenic differentiation of vascular smooth muscle cells. In patients with coronary artery disease, patients with ALDH2 rs671 gene mutation developed more severe coronary calcification. 4-HNE promoted calcification of both mouse aortic smooth muscle cells and human aortic smooth muscle cells and their osteochondrogenic differentiation in vitro. 4-HNE increased the level of Runx2 (runt-related transcription factor-2), and the effect of 4-HNE on promoting vascular smooth muscle cell calcification was ablated when Runx2 was knocked down. Mutation of Runx2 at lysine 176 reduced its carbonylation and eliminated the 4-HNE-induced upregulation of Runx2. CONCLUSIONS: Our results suggest that 4-HNE increases Runx2 stabilization by directly carbonylating its K176 site and promotes vascular calcification. ALDH2 might be a potential target for the treatment of vascular calcification.

Chinese Society of Cardiology guidelines on the diagnosis and treatment of adult fulminant myocarditis.

Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium. It is characterized by acute onset, rapid progress and high risk of death. Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm. According to China's practical experience, the adoption of the "life support-based comprehensive treatment regimen" (with mechanical circulation support and immunomodulation therapy as the core) can significantly improve the survival rate and long-term prognosis. Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.