[Predictive value of the proportion of hibernating myocardium in total perfusion defect on reverse remodeling in patients with HFrEF underwent coronary artery bypass graft].

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with 18F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with 18F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and 18F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and 18F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.

[Periodic dynamic observation and analysis of cellular and humoral immunity indexes of adults infected with Omicron BA.1].

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.

[A randomized controlled trial of indobufen versus aspirin in the prevention of bridging restenosis after coronary artery bypass grafting].

Objective: To compare the efficacy and safety between indobufen and aspirin in the prevention of restenosis of bridge vessels at 1 year after off-pump coronary artery bypass grafting. Methods: This study was a prospective cohort study. We selected 152 patients who received coronary artery bypass grafting in Beijing Anzhen Hospital from December 2016 to December 2018. Patients were divided into the indobufen group and the aspirin group. Patients in the aspirin group were treated with aspirin and clopidogrel, and patients in the indobufen group were treated with indobufen and clopidogrel. During the 1-year follow-up, the rate of restenosis of saphenous vein bridge and internal mammary artery bridge, the rate of adverse cardiac events and adverse reactions were compared between the two groups. The levels of fibrinogen (FIB), D-dimer (D-D), thrombomodulin (TM) and thrombin-activatable fibrinolysis inhibitor (TAFI) were compared before and after antiplatelet therapy. Results: There were 76 cases in the indobufen group, including 57 males (75.0%), aged (60.3±6.6) years. There were 76 cases in the aspirin group, including 62 males (81.6%), aged (59.7±7.2) years. Baseline data were comparable between the two groups (P>0.05). During the follow-up, 3 cases were lost to follow up. Follow-up was completed in 74 patients in the indobufen group and 75 in the aspirin group. A total of 268 bridging vessels were grafted in the indobufen group and 272 in the aspirin group. One year after surgery, the patency rates of great saphenous vein bridge and internal mammary artery bridge were 94.5% (189/200) and 97.1% (66/68) in the indobuphen group, and 91.3% (189/207) and 96.9% (63/65) in the aspirin group, respectively. There was no significant difference in patency rate of great saphenous vein bridge and internal mammary artery bridge between the two groups (χ²=0.282, 0.345, P>0.05). The total incidence of adverse cardiac events was 5.4% (4/74) in the indobufen group and 6.7% (5/75) in the aspirin group (χ²=0.126, P>0.05). The overall incidence of gastrointestinal adverse reactions was significantly lower in the indobufen group than in the aspirin group (4.1% (3/74) vs. 13.3% (10/75), χ²=4.547, P<0.05). The levels of FIB, D-D, TM and TAFI in the two groups were lower than those before surgery (P<0.05), and there was no statistical significance between the two groups at baseline and post-operation (P>0.05). Conclusion: The efficacy of indobufen combined with clopidogrel in the prevention of 1-year restenosis after coronary artery bypass graft is similar to that of aspirin combined with clopidogrel, but the incidence of adverse reactions is lower, and the safety is higher in patients treated with indobufen combined with clopidogrel compared to aspirin combined with clopidogrel strategy.

[Predictive value of left ventricular ejection fraction for the occurrence of postoperative myocardial infarction after coronary endarterectomy in patients with diffuse coronary artery disease].

Objective: To investigate the predictive value of ejection fraction for the postoperative myocardial infarction after coronary endarterectomy (CE) in patients with diffuse coronary artery disease (DCAD). Methods: Patients who underwent cardiac artery bypass graft (CABG) surgery and CE in Beijing Anzhen Hospital affiliated to Capital Medical University from May 2018 to December 2020 were enrolled in this prospective observational study. Baseline features including age, sex and echocardiography parameters were obtained. Left ventricular ejection fraction(EF) was measured by echocardiography. The patients were divided into postoperative myocardial infarction (PMI) group and non-PMI group according to PMI occurrence. Linear regression analysis, logistic regression model, and receiver operating characteristic(ROC) curve were used to analyze the correlation between left ventricular ejection fraction and PMI and the influencing factors. Results: A total of 120 patients were enrolled in the study. There were 32 patients (27%) in the PMI group (male 27(84%), age (62±8)), inferior myocardial infarction occurred in 24 (75%) patients. There were 88 patients (73%) in the non-PMI group (male 70(80%), age (62±8)). EF (55% (49%, 64%) vs. 62% (55%, 67%), P=0.01) was significantly lower in the PMI group than in the non-PMI group. Perioperative TNI, IABP use and length of hospitalization were significantly higher in the PMI group than in the non-PMI group. Multivariate logistic regression showed that lower EF was an independent risk factor of PMI (OR=0.93, 95%CI: 0.89-0.98, P=0.01) after adjusting age, sex and body mass index. ROC curve analysis showed that EF<60% could sufficiently predict the occurrence of PMI (AUC= 0.67, sensitivity 64%, specificity 69%, P=0.01). Linear regression analysis showed that left ventricular end-diastolic diameter (OR=-0.52, 95%CI:-1.13-0.60, P<0.001), graft flow in left anterior descending (OR=-0.20, 95%CI:-0.15-0.01, P=0.02) and history of diabetes (OR=-0.28, 95%CI:-8.25-1.85, P=0.002) were negatively correlated with preoperative EF value. Conclusion: Lower preoperative EF is an independent risk factor for PMI after CABG and CE in DCAD patients, closely related to the left ventricular end-diastolic diameter, graft flow in left anterior descending artery and diabetes mellitus.

The EEL-1 ubiquitin ligase promotes DNA damage-induced germ cell apoptosis in C. elegans.

E3 ubiquitin ligases target a growing number of pro- and anti-apoptotic proteins, including tumour suppressor p53, caspases, and the Bcl-2 family. The core apoptosis pathway is well conserved between mammals and Caenorhabditis elegans, but the extent to which ubiquitin ligases regulate apoptotic cell death is not known. To investigate the role of E3 ligases in apoptosis, we inhibited 108 of the 165 predicted E3 ubiquitin ligase genes by RNA interference and quantified apoptosis in the C. elegans germline after genotoxic stress. From this screen, we identified the homologous to E6-associated protein C terminus-domain E3 ligase EEL-1 as a positive regulator of apoptosis. Intriguingly, the human homologue of EEL-1, Huwe1/ARF-BP1/Mule/HectH9, has been reported to possess both pro- and anti-apoptotic functions through its ability to stimulate Mcl-1 and p53 degradation, respectively. Here, we demonstrate that eel-1 is required to promote DNA damage-induced germ cell apoptosis, but does not have a role in physiological germ cell apoptosis or developmental apoptosis in somatic tissue. Furthermore, eel-1 acts in parallel to the p53-like gene cep-1 and intersects the core apoptosis pathway upstream of the Bcl-2/Mcl-1 orthologue ced-9. Although ee1-1 mutants exhibit hypersensitivity to genotoxic stress they do not appear to be defective in DNA repair, suggesting a distinct role for EEL-1 in promoting damage-induced apoptosis in the germline.

The SCF FSN-1 ubiquitin ligase controls germline apoptosis through CEP-1/p53 in C. elegans.

The nematode Caenorhabditis elegans contains a single ancestral p53 family member, cep-1, which is required to activate apoptosis of germ cells in response to DNA damage. To understand how the cep-1/p53 pathway is regulated in response to genotoxic stress, we performed an RNA interference screen and identified the neddylation pathway and components of an SCF (Skp1/cullin/F-box) E3 ubiquitin ligase as negative regulators of cep-1-dependent germ cell apoptosis. Here, we show that the cullin gene cul-1, the Skp1-related gene skr-1, and the ring box genes rbx-1 and rpm-1 all negatively regulate cep-1-dependent germ cell apoptosis in response to the DNA-alkylating agent N-ethyl-N-nitrosourea (ENU). We also identified the F-box protein FSN-1, previously shown to form an SCF ligase that regulates synapse development, as a negative regulator of cep-1-dependent germline apoptosis. The hypersensitivity of fsn-1 mutants to ENU-induced germline apoptosis was completely suppressed by a cep-1 loss-of-function allele. We further provide evidence that the transcriptional activity, phosphorylation status, and levels of endogenous CEP-1 are higher in fsn-1 mutants compared with wild-type animals after ENU treatment. Our results uncover a novel role for the SCF(FSN-1) E3 ubiquitin ligase in the regulation of cep-1-dependent germ cell apoptosis.

Brain interleukin asymmetries and paw preference in mice.

The two sides of the brain are differently involved in the modulation of immune responses as demonstrated by lesion and behavioral approaches. To study the interactions between cerebral cortex cytokines and brain lateralization, three groups of BALB/c mice were selected on the basis of their performance in the paw preference test (left-pawed, ambidextrous and right-pawed) and the levels of interleukin-1beta and interleukin-6 were measured in the two cerebral cortices after an intraperitoneal saline or lipopolysaccharide. Generally, right cortices had higher interleukin-1beta and interleukin-6 levels than left cortices for both saline and lipopolysaccharide-treated mice. A strong correlation between the levels of interleukin-1beta and interleukin-6 in right and left cortices and behavioral lateralization was observed. For the saline-treated mice: in their left cortices, interleukin-1beta levels were higher for ambidextrous mice than for right-pawed mice (P<0.05); in their right cortices, interleukin-6 levels were higher for ambidextrous mice than for right-/left-pawed mice, and right-pawed mice have higher levels of interleukin-6 than left-pawed mice (P<0.01). In their left cortices, interleukin-6 levels are higher for left-pawed mice than for both ambidextrous and right-pawed mice (P<0.01). In their left cortices, interleukin-6 levels are higher for left-pawed mice than for both ambidextrous and right-pawed mice (P<0.01). The quadratic curve equations showed that the levels of interleukin-1beta and interleukin-6 in the right/left cortices had a highly significant correlation with paw preference scores in both normal and lipopolysaccharide-treated mice. In conclusion, the present report demonstrated that the basal levels of interleukin-1beta and interleukin-6 were higher in the right cortex than left cortex in mice. There was a strong correlation between the levels of interleukin-1beta and interleukin-6 and behavioral lateralization, and cytokine asymmetries had a strong correlation with the direction and the intensity of behavioral lateralization.

Strain-dependent association between lateralization and lipopolysaccharide- induced IL-1beta and IL-6 production in mice.

OBJECTIVE: The brain modulates the immune system in an asymmetrical way, as shown by the association between paw preference and immune response in the mouse. We predicted that the production of cytokines, which are one of the molecular pathways for brain-immune interactions, should be linked to lateralization in a strain-dependent manner. METHODS: We therefore measured plasma levels of interleukin (IL)-1beta and IL-6 after an intraperitoneal injection of lipopolysaccharide (LPS) in two strains of mice (C3H and BALB/c) that were selected for their different profiles of cytokine production. RESULTS: Plasma levels of IL-1beta and IL-6 increased after LPS injection in both strains and this increase was dependent on paw preference in BALB/c but not in C3H mice. Increased levels of IL-1beta were observed in left-pawed and ambidextrous but not in right-pawed mice. For IL-6, the LPS-induced increase was higher in ambidextrous than in left- and right-pawed animals. CONCLUSION: Cytokines may represent one of the factors responsible for interindividual differences in brain-immune interactions.

Hypha formation in the white-opaque transition of Candida albicans.

Cells of Candida albicans strain WO-1 and related strains switch frequently and reversibly between a white-colony-forming unit (white phase) and a gray-colony-forming unit (opaque phase). Cells in the budding white phase exhibit the usual smooth round phenotype observed in other C. albicans strains, but cells in the budding opaque phase exhibit a unique elongate shape with surface pimples or protrusions. In this study, it was demonstrated that opaque cells formed hyphae at low to negligible levels in suspension cultures but could be induced to form hyphae at high levels when anchored to the chamber wall of a perfusion chamber or to a monolayer of human skin epithelial cells. Variability in the proportion of hyphae formed between experiments appeared to be due to variability between individual opaque clones. The hyphae formed by opaque cells were morphologically identical to hyphae formed by white cells (i.e., they were devoid of pimples or protrusions and exhibited the same shape and septal locations). They also did not stain with an opaque-specific antiserum which differentially stained opaque budding cells in a punctate fashion. However, when stimulated to form buds, opaque hyphae formed opaque-shaped daughter buds, demonstrating that although they are morphologically similar to hyphae formed by white cells, they are genetically opaque.