Enzyme-loaded rod-like microgel shapes: a step towards the creation of shape-specific microreactors for blood detoxification purposes.

Rapid removal of toxic substances is crucial to restore the normal functions of our body and ensure survival. Due to their high substrate specificity and catalytic efficiency, enzymes are unique candidates to deplete toxic compounds. While enzymes display several limitations including low stability and high immunogenicity, these can be overcome by entrapping them in a diverse range of carriers. The resulting micro/nanoreactors shield the enzymes from their surroundings, preventing their misfolding or denaturation thus allowing them to conduct their function. The micro/nanoreactors must circulate in the blood stream for extended periods of time to ensure complete depletion of the toxic agents. Surprisingly, while it is widely acknowledged that non-spherical carriers exhibit longer residence time in the bloodstream than their spherical counterparts, so far, all the reported micro/nanoreactors have been assembled with a spherical architecture. Herein, we address this important issue by pioneering the first shape-specific microreactors. We use UV-assisted punching to create rod-like microgel shapes with dimensions of 8 µm × 1 µm × 2 µm and demonstrate their biocompatibility by conducting hemolysis and cell viability assays with a macrophage and an endothelial cell line. Upon encapsulation of the model enzyme ß-lactamase, the successful fabrication of rod-shaped microreactors is demonstrated by their ability to convert the yellow nitrocefin substrate into its hydrolyzed product.

Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain.

Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.

Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants.

The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines.

Risk factors for mortality in surgical patients on combined continuous renal replacement therapy and extracorporeal membrane oxygenation: single-center retrospective study.

OBJECTIVE: In patients receiving extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT) is increasingly being used for renal replacement and fluid management. However, critically ill surgical patients receiving combined ECMO and CRRT tend to have a high mortality rate, and there are limited studies on this population. Therefore, we aimed to investigate the risk factors for mortality in surgical patients receiving combined ECMO and CRRT. METHODS: Data of surgical patients who underwent ECMO between December 2013 and April 2023 were retrospectively reviewed. Univariate and multivariate logistic regression analysis were used to identify the risk variables. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff value of albumin and age to predict death. RESULTS: A total of 199 patients on ECMO support were screened, of which 105 patients were included in the final analysis. Of 105 patients, 77 (73.33%) were treated with CRRT. Veno-arterial ECMO was performed in 97 cases (92.38%), and the rest were veno-venous ECMO (n = 8, 7.62%). Cardiovascular-related surgery was performed in the main patients (n = 86, 81.90%) and other types of surgery in 19 patients. In surgical patients on ECMO support, the logistic regression analysis showed that CRRT implantation, male sex, and age were the independent risks factors for mortality. Furthermore, the ROC curve analysis showed that age 48.5 years had the highest Youden index. In surgical patients on combined CRRT and ECMO, age, valvular heart disease, and albumin were the independent risk factors for prognosis. Albumin had the highest Youden index at a cutoff value of 39.95 g/L for predicting mortality, though the overall predictive value was modest (area under ROC 0.704). Age had the highest Youden index at a cutoff value of 48.5 years for predicting mortality. CONCLUSIONS: In our cohort of surgical patients requiring ECMO, which consisted mostly of patients undergoing cardiovascular surgery requiring VA-ECMO, the need for CRRT was an independent risk factor for mortality. In the subset of patients on combined CRRT and ECMO, independent risk factors for mortality included higher age, lack of valvular heart disease, and lower serum albumin.

A pan-coronavirus peptide inhibitor prevents SARS-CoV-2 infection in mice by intranasal delivery.

Coronaviruses (CoVs) have brought serious threats to humans, particularly severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which continually evolves into multiple variants. These variants, especially Omicron, reportedly escape therapeutic antibodies and vaccines, indicating an urgent need for new antivirals with pan-SARS-CoV-2 inhibitory activity. We previously reported that a peptide fusion inhibitor, P3, targeting heptad repeated-1 (HR1) of SARS-CoV-2 spike (S) protein, could inhibit viral infections. Here, we further designed multiple derivatives of the P3 based on structural analysis and found that one derivative, the P315V3, showed the most efficient antiviral activity against SARS-CoV-2 variants and several other sarbecoviruses, as well as other human-CoVs (HCoVs). P315V3 also exhibited effective prophylactic efficacy against the SARS-CoV-2 Delta and Omicron variants in mice via intranasal administration. These results suggest that P315V3, which is in Phase II clinical trial, is promising for further development as a nasal pan-SARS-CoV-2 or pan-CoVs inhibitor to prevent or treat CoV diseases.

Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders.

Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.

Genetic mechanisms of 184 neuro-related proteins in human plasma.

Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-reiated proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-reiated traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.

Efficient Targeted Delivery of Bifunctional Circular Aptamer-ASO Chimera to Suppress the SARS-CoV-2 Proliferation and Inflammation.

Inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and excessive inflammation is the current task in the prevention and treatment of corona vireus disease 2019 (COVID-19). Here, a dual-function circular aptamer-ASO chimera (circSApt-NASO) is designed to suppress SARS-CoV-2 replication and inflammation. The chemically unmodified circSApt-NASO exhibits high serum stability by artificial cyclization. It is also demonstrated that the SApt binding to spike protein enables the chimera to be efficiently delivered into the host cells expressing ACE2 along with the infection of SARS-CoV-2. Among them, the SApt potently inhibits spike-induced inflammation. The NASO targeting to silence N genes not only display robust anti-N-induced inflammatory activity, but also achieve efficient inhibition of SARS-CoV-2 replication. Overall, benefiting from the high stability of the cyclization, antispike aptamer-dependent, and viral infection-mediate targeted delivery, the circSApt-NASO displays robust potential against authentic SARS-CoV-2 and Omicron, providing a promising specific anti-inflammatory and antiproliferative reagent for therapeutic COVID-19.

The gap and two-level differentiation in kindergarten education funding groups in China.

This paper examines the disparity in kindergarten education funding between different groups from 2012 to 2018 through the Gini coefficient and decomposition techniques. The results show that: the Gini coefficient of inter-provincial kindergarten education funding increased from 0.2320 in 2012 to 0.2329 in 2018 during the observation period; the Gini coefficients between urban and rural areas and between regions are smaller than those between provinces, but it is noteworthy that the Gini coefficient between urban and rural areas is growing faster; the gap at this stage mainly comes from the internal gap between the two items of state financial education funding and career income. The internal disparity between urban and rural areas and between regions also contributes significantly to the overall disparity; there is no obvious polarisation in kindergarten education funding. Combined with the analysis results, the following recommendations are made: increase the investment in education funds, gradually reduce the proportion of school fee income in career income, financial resources should be tilted toward kindergartens in regions with relatively slow economic development, and financial resources should be appropriately distributed between public and private kindergartens.

Contribution of CRISPRable DNA to human complex traits.

CRISPR-Cas is a powerful genome editing tool for various species and human cell lines, widely used in many research areas including studying the mechanisms, targets, and gene therapies of human diseases. Recent developments have even allowed high-throughput genetic screening using the CRISPR system. However, due to the practical and ethical limitations in human gene editing research, little is known about whether CRISPR-editable DNA segments could influence human complex traits or diseases. Here, we investigated the human genomic regions condensed with different CRISPR Cas enzymes' protospacer-adjacent motifs (PAMs). We found that Cas enzymes with GC-rich PAMs could interfere more with the genomic regions that harbor enriched heritability for human complex traits and diseases. The results linked GC content across the genome to the functional genomic elements in the heritability enrichment of human complex traits. We provide a genetic overview of the effects of high-throughput genome editing on human complex traits.

Genetic Landscape of the ACE2 Coronavirus Receptor.

BACKGROUND: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood. METHODS: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data. RESULTS: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells. CONCLUSIONS: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.

M2b macrophages stimulate lymphangiogenesis to reduce myocardial fibrosis after myocardial ischaemia/reperfusion injury.

CONTEXT: Therapeutic lymphangiogenesis is a new treatment for cardiovascular diseases. Our previous study showed M2b macrophages can alleviate myocardial ischaemia/reperfusion injury (MI/RI). However, the relation between M2b macrophages and lymphangiogenesis is not clear. OBJECTIVE: To investigate the effects of M2b macrophages on lymphangiogenesis after MI/RI. MATERIALS AND METHODS: Forty male Sprague-Dawley (SD) rats were randomized into Sham operation group (control, n = 8), MI/RI group (n = 16) and M2b macrophage transplantation group (n = 16). M2b macrophages (1 × 106) in 100 µL of normal saline or the same volume of vehicle was injected into the cardiac ischaemic zone. Two weeks later, echocardiography and lymphatic counts were performed, and the extent of myocardial fibrosis and the expression of vascular endothelial growth factor C (VEGFC) and VEGF receptor 3 (VEGFR3) were determined. In vitro, lymphatic endothelial cells (LECs) were cultured with M2b macrophages for 6-24 h, and the proliferation, migration and tube formation of the LECs were assessed. RESULTS: In vivo, M2b macrophage transplantation increased the level of lymphangiogenesis 2.11-fold, reduced 4.42% fibrosis, improved 18.65% left ventricular ejection fraction (LVEF) and upregulated the expressions of VEGFC and VEGFR3. In vitro, M2b macrophage increased the proliferation, migration, tube formation and VEGFC expression of LECs. M2b macrophage supernatant upregulated VEGFR3 expression of LECs. DISCUSSION AND CONCLUSIONS: Our study shows that M2b macrophages can promote lymphangiogenesis to reduce myocardial fibrosis and improve heart function, suggesting the possible use of M2b macrophage for myocardial protection therapy.

Preoperative serum albumin: a promising indicator of early mortality after surgery for infective endocarditis.

BACKGROUND: Despite novel improvements in the diagnosis and treatment of infective endocarditis (IE), there has been no significant improvement in the survival rate of IE, which indicates that many details still need to be optimized in the preoperative assessment. We sought to evaluate preoperative serum albumin as a biomarker for predicting early mortality after IE surgery. METHODS: Between October 2013 and June 2019, patients with a definite diagnosis of IE were enrolled in this study. Patients' albumin levels at admission were used as the preoperative albumin levels. Restricted cubic spline and multivariate logistic regression analyses were performed to evaluate the relationship between albumin and early mortality. Receiver operating characteristic curve analyses were performed to assess the role of albumin in predicting early mortality and compare the predictive capacity of traditional models with models that included albumin. RESULTS: Of the 276 IE patients, 20 (7.2%) died in hospital or within 30 days of surgery. Hypoalbuminemia (an albumin level <3.5 g/dL) was present in 109 (39.5%) patients. The multivariate logistic regression analysis showed that preoperative albumin was inversely associated with early mortality [adjusted odds ratio (OR) =0.22 per 1 g/dL, 95% confidence interval (CI): 0.07-0.65, P=0.006] after full adjustment. Preoperative albumin had value in predicting early mortality [area under the curve (AUC) =0.72, 95% CI: 0.61-0.84; P<0.01]. After adding albumin to the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Charlson score, the predictive ability of the model was further improved (EuroSCORE II: AUC =0.55; 95% CI: 0.42-0.67 to AUC =0.72; 95% CI: 0.61-0.84; Charlson score: AUC =0.73; 95% CI: 0.64-0.83 to AUC =0.78; 95% CI: 0.68-0.88). CONCLUSIONS: Preoperative serum albumin is inversely associated with early mortality after IE surgery, and is a promising prognostic indicator in preoperative risk stratification assessments of IE patients.

The multivariable prognostic models for severe complications after heart valve surgery.

BACKGROUND: To provide multivariable prognostic models for severe complications prediction after heart valve surgery, including low cardiac output syndrome (LCOS), acute kidney injury requiring hemodialysis (AKI-rH) and multiple organ dysfunction syndrome (MODS). METHODS: We developed multivariate logistic regression models to predict severe complications after heart valve surgery using 930 patients collected retrospectively from the first affiliated hospital of Sun Yat-Sen University from January 2014 to December 2015. The validation was conducted using a retrospective dataset of 713 patients from the same hospital from January 2016 to March 2017. We considered two kinds of prognostic models: the PRF models which were built by using the preoperative risk factors only, and the PIRF models which were built by using both of the preoperative and intraoperative risk factors. The least absolute shrinkage selector operator was used for developing the models. We assessed and compared the discriminative abilities for both of the PRF and PIRF models via the receiver operating characteristic (ROC) curve. RESULTS: Compared with the PRF models, the PIRF modes selected additional intraoperative factors, such as auxiliary cardiopulmonary bypass time and combined tricuspid valve replacement. Area under the ROC curves (AUCs) of PRF models for predicting LCOS, AKI-rH and MODS are 0.565 (0.466, 0.664), 0.688 (0.62, 0.757) and 0.657 (0.563, 0.751), respectively. As a comparison, the AUCs of the PIRF models for predicting LOCS, AKI-rH and MODS are 0.821 (0.747, 0.896), 0.78 (0.717, 0.843) and 0.774 (0.7, 0.847), respectively. CONCLUSIONS: Adding the intraoperative factors can increase the predictive power of the prognostic models for severe complications prediction after heart valve surgery.

Synthesis of Nanoparticles Fully Made of Hemoglobin with Antioxidant Properties: A Step toward the Creation of Successful Oxygen Carriers.

Transfusion of donor red blood cells (RBCs) is a crucial and widely employed clinical procedure. However, important constraints of blood transfusions include the limited availability of blood, the need for typing and cross-matching due to the RBC membrane antigens, the limited storage lifetime, or the risk for disease transmission. Hence, a lot of effort has been devoted to develop RBC substitutes, which are free from the limitations of donor blood. Despite the potential, the creation of hemoglobin (Hb)-based oxygen carriers is still facing important challenges. To allow for proper tissue oxygenation, it is essential to develop carriers with high Hb loading since Hb comprises about 96% of the RBCs' dry weight. In this work, nanoparticles (NPs) fully made of Hb are prepared by the desolvation precipitation method. Several parameters are screened (i.e., Hb concentration, desolvation ratio, time, and sonication intensity) to finally obtain Hb-NPs with a diameter of ∼568 nm and a polydispersity index (PDI) of 0.2. A polydopamine (PDA) coating is adsorbed to prevent the disintegration of the resulting Hb/PDA-NPs. Due to the antioxidant character of PDA, the Hb/PDA-NPs are able to deplete two harmful reactive oxygen species, namely, the superoxide radical anion and hydrogen peroxide. Such antioxidant protection also translates into minimizing the oxidation of the entrapped Hb to nonfunctional methemoglobin (metHb). This is a crucial aspect since metHb conversion also results in inflammatory reactions and dysregulated vascular tone. Finally, yet importantly, the reported Hb/PDA-NPs are also both hemo- and biocompatible and preserve the reversible oxygen-binding and releasing properties of Hb.

Association of Post-operative Systolic Blood Pressure Variability With Mortality After Coronary Artery Bypass Grafting.

Background: Blood pressure variability (BPV) has long been considered a risk factor for cardiovascular events. We aimed to investigate whether post-operative systolic BPV was associated with early and late all-cause mortality in patients undergoing coronary artery bypass grafting (CABG). Methods: Clinical variables and blood pressure records within the first 24 h in the post-operative intensive care unit stay from 4,509 patients operated on between 2001 and 2012 were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. BPV was measured as the coefficient of the variability of systolic blood pressure, and we compared patients in the highest quartile with patients in the other three quartiles. Results: After full adjustment, patients in the highest quartile of BPV were at a higher risk of intensive care unit mortality (OR = 2.02, 95% CI: 1.11-3.69), 30-day mortality (OR = 1.92, 95% CI: 1.22-3.02), and 90-day mortality (HR = 1.64, 95% CI: 1.19-2.27). For 2,892 patients with a 4-year follow-up, the association between a higher post-operative BPV and the risk of 4-year mortality was not significant (HR = 1.17, 95% CI: 0.96-1.42). The results were supported by the comparison of survival curves and remained generally consistent in the subgroup analyses and sensitivity analyses. Conclusions: Our findings demonstrated that in patients undergoing CABG, a higher post-operative BPV was associated with a higher risk of early mortality while the association was not significant for late mortality. Post-operative BPV can support doctors in identifying patients with potential hemodynamic instability and making timely clinical decisions.

QTL Mapping and Favorable Allele Mining of Nitrogen Deficiency Tolerance Using an Interconnected Breeding Population in Rice.

Nitrogen is one of the most important nutrients for rice growth and development. Breeding of nitrogen deficiency tolerance (NDT) variety is considered to be the most economic measure to solve the constrain of low nitrogen stress on grain yield in rice. An interconnected breeding (IB) population of 497 lines developed using Huanghuazhan (HHZ) as the recurrent parent and eight elite lines as the donor parents were tested for five traits including grain yield, biomass, harvest index, thousand grain weight, and spikelet fertility under two nitrogen treatments in three growing seasons. Association analysis using 7,388 bins generated by sequencing identified a total of 14, 14, and 12 QTLs for the five traits under low nitrogen (LN), normal nitrogen (NN), and LN/NN conditions, respectively, across three seasons. Favorable alleles were dissected for the 40 QTLs at the 10 NDT regions, and OM1723 was considered as the most important parent with the highest frequency of favorable alleles contributing to NDT-related traits. Six superior lines all showed significantly higher GY in LN environments and similar GY under NN environments except for H10. Substitution mapping using near-isogenic introgression lines delimited the qTGW2-1, which was identified on chromosome 2 under LN, NN, and LN/NN conditions into two QTLs, which were located in the two regions of about 200 and 350 kb with different favorable alleles. The bins 16, 1301, 1465, 1486, 3464, and 6249 harbored the QTLs for NDT detected in this study, and the QTLs/genes previously identified for NDT or nitrogen use efficiency (NUE) could be used for enhancing NDT and NUE by marker-assisted selection (MAS).

Increased glucose variability is associated with major adverse events in patients with infective endocarditis undergo surgical treatment.

BACKGROUND: This study aimed to investigate the prognostic value of glucose variability (GV) in predicting postoperative major adverse events (MAEs) in patients with infective endocarditis (IE) who underwent surgical treatment. METHODS: This retrospective observational study included a total of 381 consecutive patients who underwent surgical treatment in our institution from October 2007 to August 2019. The MAEs included all-cause death, stroke, myocardial infarction, acute heart failure, IE recurrence, acute renal failure and sepsis. Postoperative GV in the first 24 hours was measured by the mean 24-hour glucose, standard deviation, coefficient of variation (CV) and mean amplitude of glycemic excursions. Univariate and multivariate logistic regression analyses were performed to identify the independent association of GV with MAEs. RESULTS: Of the 381 patients, 79 (20.7%) developed MAEs. The 30-day mortality of the overall study cohort was 5.23%. The multivariate logistic regression analysis indicated that 24-hour GV, measured as the CV [odds ratio (OR) =1.49, 95% CI, 1.23-3.57, P=0.012], was significantly associated with MAEs in IE patients. For every 10% increase in 24-hour CV, there was a 49% increase in the risk of MAEs. Furthermore, compared to patients in the low tertile of GV, patients in the top tertile of 24-hour GV had a higher 30-day mortality and an increased incidence of heart failure and hemodialysis as well as longer ventilation support. CONCLUSIONS: The results of this retrospective investigation demonstrated that increased GV measured by CV is an independent predictor of postoperative MAEs in patients undergoing surgical treatment for IE.