Persistence of SARS-CoV-2 colonization and high expression of inflammatory factors in cardiac tissue 6 months after COVID-19 recovery: a prospective cohort study.

Background: The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in myocardial autopsy tissues has been observed in certain individuals with coronavirus disease 2019 (COVID-19). However, the duration of cardiac involvement remains uncertain among recovered COVID-19 patients. Our study aims to evaluate the long-term persistence of SARS-CoV-2 within cardiac tissue. Methods: We prospectively and consecutively evaluated the patients undergoing mitral valve replacement (MVR) and left atrial (LA) volume reduction surgery from May 25 to June 10, 2023 at our center, who had been approximately 6 months of recovery after Omicron wave. Patients tested positive for SARS-CoV-2 upon admission were excluded. The surgical LA tissue was collected in RNA preservation solution and stored at -80 ℃ immediately. Then SARS-CoV-2, interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) RNA expression in LA tissues were assessed through thrice-repeated reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Categorical variables were assessed using the Chi-square or Fisher's exact tests, and continuous variables was analyzed using the Mann-Whitney U test. Results: Nine of 41 patients were enrolled, all of whom tested negative for SARS-CoV-2 upon admission (two antigen and PCR tests). In four of nine patients, SARS-CoV-2 RNA was detected in their LA tissue, indicating viral colonization. Among the four positive cases, the IL-6 and IL-1ß relative expression levels in the LA tissue of one patient were increased approximately 55- and 110-fold, respectively, compared to those of SARS-CoV-2 (-) patients. Increased expression of IL-6 and IL-1ß were observed in the myocardium of this patient. Another patient demonstrated a remarkable 7-fold increase in both IL-6 and IL-1ß expression, surpassing that of SARS-CoV-2 (-) patients. Additionally, no other cardiac inflammation-related diseases or conditions were presented in these two patients. The IL-6 and IL-1ß expression levels of the remaining two patients were not significantly different from those of SARS-CoV-2 (-) patients. The relative expression levels of IL-6 and IL-1ß in cardiac tissues of all SARS-CoV-2 (-) patients were relatively low. Interestingly, despite abnormally elevated levels of IL-6 and IL-1ß within their cardiac tissue, two patients did not show a significant increase in serum IL-6 and IL-1ß levels when compared to other patients. Conclusions: Our research suggests that certain COVID-19-recovered patients have persistent colonization of SARS-CoV-2 in their cardiac tissue, accompanied by a local increase in inflammatory factors.

A new minimal invasive technique with in-situ stent-graft fenestration for type A aortic dissection.

Background: Aortic surgery successfully improves the prognosis of patients with type A aortic dissection. However, total arch replacement and reconstruction remain challenging. This study presents a new surgical modality, the in-situ stent-graft fenestration (ISSF) technique, for simplifying aortic arch reconstruction and assesses its short-term efficacy and safety in patients with type A aortic dissection. Methods: Data from 177 patients with type A aortic dissection who underwent aortic arch reconstruction were retrospectively analyzed. Sun's procedure was performed in 90 patients and ISSF was performed in the other 87. Results: The in-hospital mortality rate was 7.8% in the Sun's procedure group and 3.4% in the ISSF group (p = 0.357). Compared to the Sun's procedure group, the ISSF group had significantly shorter surgical duration, cardiopulmonary bypass time, circulatory arrest time, mechanical ventilation time, and aortic cross-clamp time (p < 0.05). Additionally, intraoperative blood loss was lower in the ISSF group than in the Sun's procedure group (p < 0.05). Patients who underwent ISSF also had a lower incidence of postoperative complications, including lung injury, renal failure, peripheral nerve injury, and chylothorax, than those who underwent Sun's procedure (p < 0.05). During the 6-month follow-up period after surgery, both groups showed significant improvements in the true lumen diameter of the descending thoracic aorta post-operation compared with the pre-operation measurements; meanwhile, the false lumen diameter decreased (p < 0.05). Conclusions: The ISSF technique appears to be an effective and safe alternative to conventional surgical procedures for patients with type A aortic dissection, with the potential to simplify the procedure, shorten the operation time, and yield satisfactory operative results. However, further investigation is needed to determine its long-term benefits.

Systematic review of the effect of cerebrospinal fluid drainage on outcomes after endovascular type B aortic dissection repair.

OBJECTIVE: The aim of the present systematic review was to determine whether prophylactic use of cerebrospinal fluid drainage (CSFD) contributes to a lower rate of spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched to identify all relevant studies reported before May 7, 2023. A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO registration no. CRD42023441392). The primary outcome was permanent SCI. Secondary outcomes were temporary SCI and 30-day/in-hospital mortality. The data were presented as the pooled event rates (ERs) and 95% confidence intervals (CIs). RESULTS: A total of 1008 studies were screened, of which 34 studies with 2749 patients were included in the present analysis. The mean Downs and Black quality assessment score was 8.71 (range, 5-12). The pooled rate of permanent SCI with prophylactic CSFD was identical to that without prophylactic CSFD (2.0%; 95% CI, 1.0-3.0; P = 0.445). No statistically significant difference was found between the rates of permanent SCI with routine vs. selective prophylactic CSFD (P = 0.596). The pooled rate of temporary SCI was 1.0% (95% CI, 0.00-1.0%). The pooled rate for 30-day or in-hospital mortality was not significantly different (P = 0.525) in patients with prophylactic CSFD (4.0, 95% CI 2.0-6.0) or without prophylactic CSFD (5.0, 95% CI 2.0-7.0). CONCLUSIONS: The systematic review has shown that prophylactic CSFD was not associated with a lower rate of permanent SCI and 30-day or in-hospital mortality after TEVAR for TBAD.

Early outcome of simplified total arch reconstruction under mild hypothermia (30-32 °C) with distal aortic perfusion.

OBJECTIVE: We designed a simplified total arch reconstruction (s-TAR) technique which could be performed under mild hypothermia (30-32 °C) with distal aortic perfusion. This study aimed to compare its efficacy of organ protection with the conventional total arch reconstruction (c-TAR). METHODS: We reviewed the clinical data of 195 patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and TAR procedure between January 2018 and December 2022 in our center. 105 received c-TAR under moderate hypothermia (25-28 °C) with circulatory arrest (c-TAR group); rest 90 received s-TAR under mild hypothermia (30-32 °C) with distal aortic perfusion (s-TAR group). RESULTS: The s-TAR group demonstrated shorter CPB time, cross-clamp time and lower body circulatory arrest time compared with the c-TAR group. The 30-day mortality was 2.9% for the c-TAR group and 1.1% for the s-TAR group (P = 0.043). The mean duration of mechanical ventilation was shorter in the s-TAR group. Paraplegia was observed in 4 of 105 patients (3.8%) in the c-TAR group, while no such events were observed in the s-TAR group. The incidence of temporary neurologic dysfunction was significantly higher in the c-TAR group. The incidence of permanent neurologic dysfunction also showed a tendency to be higher in the c-TAR group, without statistical significance. Furthermore, the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The rate of postoperative hepatic dysfunction and all grades of AKI was remarkably lower in the s-TAR group. The 3-year survival rate was 95.6% in the s-TAR group and 91.4% in the c-TAR group. CONCLUSIONS: s-TAR under mild hypothermia (30-32℃) with distal aortic perfusion is associated with lower mortality and morbidity, offering better neurological and visceral organ protection compared with c-TAR.

Effect of High-Flow Nasal Cannula for Hypoxemia Following Sun's Procedure in Acute Aortic Dissection Type a Patients.

Background: Patients with acute aortic dissection type A (AADA) often have hypoxemia (partial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2] <300 mmHg) before weaning in the intensive care unit (ICU). This study compared the efficacy of high-flow nasal cannula (HFNC) with that of conventional oxygen therapy (COT) in patients with AADA following Sun's procedure. Methods: The medical records of 87 adult patients with AADA who underwent Sun's procedure and met the inclusion criteria (PaO2/FiO2 <300 mmHg before weaning) were retrospectively analyzed. After surgery, 41 patients were treated with HFNC and 46 were treated with COT. The oxygenation level, FiO2, partial pressure of carbon dioxide, heart rate, respiratory rate, subjective discomfort, and reintubation rate were recorded. The difference in lung volume loss between the HFNC and COT groups was assessed using the radiological atelectasis score (chest radiograph) or calculated from three-dimensional (3D) reconstructed computed tomography (CT) images. Results: From day 1 to day 5 after weaning, there was no significant difference in PaO2/FiO2 between the HFNC and COT groups, although the FiO2 was significantly lower in the HFNC group than in the COT group (P < 0.05). Further studies indicated that the percentage of lung volume loss (pleural effusion and/or pulmonary atelectasis) by 3D reconstruction of CT images at 4-8 days post-operation was significantly lower in the HFNC group (P < 0.05). The subjective experience of breathing discomfort, reintubation rate, and length of stay in the ICU were significantly reduced in the HFNC group (P < 0.05). There was no significant difference in readmission to the ICU and in-hospital mortality between the two groups. Conclusions: HFNC can be used as an effective oxygen therapy for AADA patients with hypoxemia after Sun's procedure.

C/EBPß Acts Upstream of NF-κB P65 Subunit in Ox-LDL-Induced IL-1ß Production by Macrophages.

BACKGROUND/AIMS: Interleukin-1ß (IL-1ß) is one of the critical inflammatory factors during atherogenesis. CCAAT/enhancer binding proteins ß (C/EBPß), a regulator of IL-1ß production, recently been evidenced as a key player in the development of atherosclerosis. However, the mechanisms of how C/EBPß regulates the production of IL-1ß are unclear. In this study, we aimed to explore the role of C/EBPß in regulating IL-1ß production in macrophages after oxidized low-density lipoprotein (ox-LDL) exposure and the underlying mechanisms. METHODS: RAW264.7 macrophages were treated with 0, 25, 50 or 100 µg/ml ox-LDL for 12, 24 or 48 h. Small interfering RNAs were used to silence related proteins. The gene and protein expression levels were determined by quantitative real-time polymerase chain reaction or western blot (WB). IL-1ß secretion was assessed by enzyme-linked immunosorbent assay. The cytoplasmic and nuclear proteins were evaluated by nuclear fractionation followed by WB. Localization of p65 was observed by immunofluorescence. The binding activity of p65 to IL-1ß was tested by dual-luciferase reporter assay. RESULTS: Ox-LDL increased IL-1ß production, accompanied with increasing C/EBPß and p65 expression in a dose- and time-dependent manner. Moreover, C/EBPß deficiency in macrophages blocked ox-LDL-induced increases in IL-1ß expression, maturation as well as p65 activation. However, p65 deficiency inhibited the increase in IL-1ß production, but not C/EBPß expression. Dual-luciferase reporter results showed that overexpression of C/EBPß significantly enhanced binding activity of p65 to IL-1ß promoter. In addition, C/EBP 1ß deficiency in macrophages abolished the ox-LDL-induced gene transcription increases of IL-1ß, IL-6, p65 and caspase-1. CONCLUSIONS: Our results demonstrate that C/EBPß acts upstream of NF-κB p65 subunit in ox-LDL-induced IL-1ß production in macrophages and may regulate IL-1ß maturation by promoting caspase-1. C/EBPß may be a promising candidate for the prevention and treatment of atherosclerosis.

Store-operated calcium entry-activated autophagy protects EPC proliferation via the CAMKK2-MTOR pathway in ox-LDL exposure.

Improving biological functions of endothelial progenitor cells (EPCs) is beneficial to maintaining endothelium homeostasis and promoting vascular re-endothelialization. Because macroautophagy/autophagy has been documented as a double-edged sword in cell functions, its effects on EPCs remain to be elucidated. This study was designed to explore the role and molecular mechanisms of store-operated calcium entry (SOCE)-activated autophagy in proliferation of EPCs under hypercholesterolemia. We employed oxidized low-density lipoprotein (ox-LDL) to mimic hypercholesterolemia in bone marrow-derived EPCs from rat. Ox-LDL dose-dependently activated autophagy flux, while inhibiting EPC proliferation. Importantly, inhibition of autophagy either by silencing Atg7 or by 3-methyladenine treatment, further aggravated proliferative inhibition by ox-LDL, suggesting the protective effects of autophagy against ox-LDL. Interestingly, ox-LDL increased STIM1 expression and intracellular Ca2+ concentration. Either Ca2+ chelators or deficiency in STIM1 attenuated ox-LDL-induced autophagy activation, confirming the involvement of SOCE in the process. Furthermore, CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, ß) activation and MTOR (mechanistic target of rapamycin [serine/threonine kinase]) deactivation were associated with autophagy modulation. Together, our results reveal a novel signaling pathway of SOCE-CAMKK2 in the regulation of autophagy and offer new insights into the important roles of autophagy in maintaining proliferation and promoting the survival capability of EPCs. This may be beneficial to improving EPC transplantation efficacy and enhancing vascular re-endothelialization in patients with hypercholesterolemia.

Protein submitochondrial localization from integrated sequence representation and SVM-based backward feature extraction.

Mitochondrion, a tiny energy factory, plays an important role in various biological processes of most eukaryotic cells. Mitochondrial defection is associated with a series of human diseases. Knowledge of the submitochondrial locations of proteins can help to reveal the biological functions of novel proteins, and understand the mechanisms underlying various biological processes occurring in the mitochondrion. However, experimental methods to determine protein submitochondrial locations are costly and time consuming. Thus it is essential to develop a fast and reliable computational method to predict protein submitochondrial locations. Here, we proposed a support vector machine (SVM) based approach for predicting protein submitochondrial locations. Information from the position-specific score matrix (PSSM), gene ontology (GO) and the protein feature (PROFEAT) was integrated into the principal features of this model. Then a recursive feature selection scheme was employed to select the optimal features. Finally, an SVM module was used to predict protein submitochondrial locations based on the optimal features. Through the jackknife cross-validation test, our method achieved an accuracy of 99.37% on benchmark dataset M317, and 100% on the other two datasets, M1105 and T86. These results indicate that our method is economic and effective for accurate prediction of the protein submitochondrial location.