Analyses of lncRNA and mRNA profiles in recurrent atrial fibrillation after catheter ablation.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Catheter ablation has become a crucial treatment for AF. However, there is a possibility of atrial fibrillation recurrence after catheter ablation. Our study sought to elucidate the role of lncRNA‒mRNA regulatory networks in late AF recurrence after catheter ablation. METHODS: We conducted RNA sequencing to profile the transcriptomes of 5 samples from the presence of recurrence after AF ablation (P-RAF) and 5 samples from the absence of recurrence after AF ablation (A-RAF). Differentially expressed genes (DEGs) and long noncoding RNAs (DE-lncRNAs) were analyzed using the DESeq2 R package. The functional correlations of the DEGs were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein‒protein interaction (PPI) network was constructed using STRING and Cytoscape. We also established a lncRNA‒mRNA regulatory network between DE-lncRNAs and DEGs using BEDTools v2.1.2 software and the Pearson correlation coefficient method. To validate the high-throughput sequencing results of the hub genes, we conducted quantitative real-time polymerase chain reaction (qRT‒PCR) experiments. RESULTS: A total of 28,528 mRNAs and 42,333 lncRNAs were detected. A total of 96 DEGs and 203 DE-lncRNAs were identified between the two groups. GO analysis revealed that the DEGs were enriched in the biological processes (BPs) of "regulation of immune response" and "regulation of immune system process", the cellular components (CCs) of "extracellular matrix" and "cell‒cell junction", and the molecular functions (MFs) of "signaling adaptor activity" and "protein-macromolecule adaptor activity". According to the KEGG analysis, the DEGs were associated with the "PI3K-Akt signaling pathway" and "MAPK signaling pathway." Nine hub genes (MMP9, IGF2, FGFR1, HSPG2, GZMB, PEG10, GNLY, COL6A1, and KCNE3) were identified through the PPI network. lncRNA-TMEM51-AS1-201 was identified as a core regulator in the lncRNA‒mRNA regulatory network, suggesting its potential impact on the recurrence of AF after catheter ablation through the regulation of COL6A1, FGFR1, HSPG2, and IGF2. CONCLUSIONS: The recurrence of atrial fibrillation after catheter ablation may be associated with immune responses and fibrosis, with the extracellular matrix playing a crucial role. TMEM51-AS1-201 has been identified as a potential key target for AF recurrence after catheter ablation.

Gene modules and genes associated with postoperative atrial fibrillation: weighted gene co-expression network analysis and circRNA-miRNA-mRNA regulatory network analysis.

Background: Atrial fibrillation (AF) is the most common complication in patients undergoing cardiac surgery. However, the pathogenesis of postoperative AF (POAF) is elusive, and research related to this topic is sparse. Our study aimed to identify key gene modules and genes and to conduct a circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory network analysis of POAF on the basis of bioinformatic analysis. Methods: The GSE143924 and GSE97455 data sets from the Gene Expression Omnibus (GEO) database were analyzed. Weighted gene co-expression network analysis (WGCNA) was used to identify the key gene modules and genes related to POAF. A circRNA-miRNA-mRNA regulatory network was also built according to differential expression analysis. Functional enrichment analysis was further performed according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: WGCNA identified 2 key gene modules and 44 key genes that were significantly related to POAF. Functional enrichment analysis of these key genes implicated the following important biological processes (BPs): endosomal transport, protein kinase B signaling, and transcription regulation. The circRNA-miRNA-mRNA regulatory network suggested that KLF10 may take critical part in POAF. Moreover, 2 novel circRNAs, hsa_circRNA_001654 and hsa_circRNA_005899, and 2 miRNAs, hsa-miR-19b-3p and hsa-miR-30a-5p, which related with KLF10, were involved in the network. Conclusions: Our study provides foundational expression profiles following POAF based on WGCNA. The circRNA-miRNA-mRNA network offers insights into the BPs and underlying mechanisms of POAF.

Infection caused by Cupriavidus gilardii in a convalescent COVID-19 patient.

Cupriavidus gilardii is an aerobic, gram-negative bacillus that can opportunistically infect immunocompromised patients or those undergoing invasive procedures. We reported a case caused by C. gilardii in a previously basic healthy 78-year-old male, who had COVID-19 and had used corticosteroids recently. The bacterium was identified as C. gilardii by the metagenomic next-generation sequencing from the patient's bronchoalveolar lavage fluid and blood. In addition, this is the first time that we isolated C. gilardii from bronchoalveolar lavage fluid, which provides clinical experience in rare bacterial infections.

[Critical coronavirus disease 2019 caused by Delta variant: a case report with literature review].

OBJECTIVE: To investigate the curative efficacy and application value of convalescent plasma (CP) in severe and critical coronavirus disease 2019 (COVID-19) caused by Delta variant. METHODS: The treatment process and results of CP therapy for a patient with critical COVID-19 caused by Delta variant were reported. The clinical application value of CP for COVID-19 caused by Delta variant was analyzed along with the literature review. RESULTS: Our case was a 50-year-old male, who was imported from abroad and had not been vaccinated against COVID-19. The novel coronavirus nucleic acid test was negative before entry. On the second day after entry, fever occurred, novel coronavirus nucleic acid test was positive. Chest CT images showed bilateral multiple mottling and ground-glass opacity with symptoms of nausea, headache, loss of appetite, diarrhea, but no running nose, nasal obstruction, dyspnea, abnormal smell and taste. The infection rapidly developed from medium to critical. On the basis of standard treatment, Delta variant CP was intravenous dripped on the 10th day of hospital admission (the 6th day after becoming severe). The patient's condition improved rapidly. CONCLUSIONS: The curative efficacy evaluation of this patient proved that CP therapy is of great value in the treatment of severe and critical COVID-19.

SIRT3-mediated mitochondrial autophagy in refeeding syndrome-related myocardial injury in sepsis rats.

Background: Myocardial injury induced by refeeding syndrome (RFS) is one of the important causes of deterioration in critically ill patients. Sirtuin-3 (SIRT3) has been shown to regulate mitochondrial autophagy in myocardial ischemia/reperfusion injury; however, the role of mitochondrial autophagy on RFS-related myocardial injury in patients in critical condition has not been reported on. Methods: Thirty Sprague-Dawley (SD) rats were divided into 3 groups (n=10 each group): the control group; the standard calorie refeeding (SCR) group; and the low calorie refeeding (LCR) group. The rats were weighed every third or four days from day 1 to day 14. On day 14, all rats were anesthetized and received an echocardiography test. Blood and bronchoalveolar lavage fluid (BALF) were collected and tested for arterial oxygen pressure (PaO2), phosphorus (P), and calcium (Ca), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin 1 (cTnI), myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and IL-6. The histopathological change of hearts and lungs were evaluated, and lung injury score was calculated. Mitochondrial autophagy related proteins (including Beclin1, LC3, mitofusin-2, Mfn2, PINK1, Parkin, and SIRT3) were analyzed using a Western blot. To evaluate the effect of SIRT3, 20 rats were divided into 2 groups (n=10 each group): The adeno-associated virus 9 (AAV9-Nc) group; and the AAV9-SIRT3 overexpression (AAV9-SIRT3) group. The protocols for rats were the same as the SCR group since day 22 after injection of AAV9. The protein expressions of PINK1, Parkin, and SIRT3 were compared between the AAV9-Nc group and AAV9-SIRT3 group. Results: SCR caused significant decline in cardiac contractility and increased inflammatory cell infiltration in myocardial tissue. Meanwhile, Beclin1, LC3, PINK1, Parkin, and SIRT3 levels decreased, while Mfn2 showed no significant change. Furthermore, significant positive correlations were also found between SIRT3 and P, PINK1, and Parkin, and significant negative correlations were found between SIRT3 and CK-MB, LDH, and cTnI. Overexpression of SIRT3 activated the PINK1/Parkin mediated mitochondrial autophagy. Conclusions: SIRT3 has an essential role in RFS-related myocardial injury during LPS induced chronic sepsis in rats, probably via regulating mitochondrial autophagy.

Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induces uncontrolled and self-amplified pulmonary inflammation, and has high morbidity and mortality rates in critically ill patients. In recent years, many bioactive ingredients extracted from herbs have been reported to effectively ameliorate ALI/ARDS via different mechanisms. Ferroptosis, categorized as regulated necrosis, is more immunogenic than apoptosis and contributes to the progression of ALI. In this study, we examined the impact of panaxydol (PX), isolated from the roots of Panax ginseng, on lipopolysaccharide (LPS)-induced ALI in mice. METHODS: In vivo, the role of PX on LPS-induced ALI in mice was tested by determination of LPS-induced pulmonary inflammation, pulmonary edema and ferroptosis. In vitro, BEAS-2B cells were used to investigate the molecular mechanisms by which PX functions via determination of inflammation, ferroptosis and their relationship. RESULTS: Administration of PX protected mice against LPS-induced ALI, including significantly ameliorated lung pathological changes, and decreased the extent of lung edema, inflammation, and ferroptosis. In vitro, PX inhibited LPS-induced ferroptosis and inflammation in bronchial epithelial cell line BEAS-2B cells. The relationship between ferroptosis and inflammation was investigated. The results showed that ferroptosis mediated inflammation in LPS-treated BEAS-2B cells, and PX might ameliorate LPS-induced inflammation via inhibiting ferroptosis. Meanwhile, PX could upregulate Keap1-Nrf2/HO-1 pathway, and selective inhibition of Keap1-Nrf2/HO-1 pathway significantly abolished the anti-ferroptotic and anti-inflammatory functions of PX in LPS-treated cells. CONCLUSION: PX attenuates ferroptosis against LPS-induced ALI via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ALI.

Can the preoperative nutritional risk score be a predictor of the outcomes in critically ill patients of lung transplantation: a retrospective study.

BACKGROUND: Nutritional Risk Screening 2002 (NRS2002) and prognostic nutrition index (PNI) are nutritional risk screening instruments that are also used to predict the complications and morbidity after surgery. Our study aims to evaluate whether preoperative nutrition status at admission or postoperative nutrition treatment during admission for lung transplantation (LTX) was linked to clinical outcomes. METHODS: This study is a retrospective observational cohort study of 42 patients undergoing LTX. Using PNI and NRS-2002 screening instruments, patients were tested for dietary danger upon admission. Univariate and multivariate analyzes were performed to investigate the independent nutritional risk predictive value for post-operative complications, hospital length or intensive care unit (ICU) stay, and mortality. RESULTS: Age, the average calorie intake, parenteral nutrition within 7 days, furosemide, the time of postoperative mechanical ventilation (MV), postoperative extracorporeal membrane oxygenation (ECMO) between survivor and non-survivor had a significant difference. Univariate analyses of death in LTX, age [HR 1.06 (1.00-1.13), P=0.04], the average calorie intake first 3 days [HR 0.99 (0.99-1.00), P=0.02], parenteral nutrition within 7 days [HR 0.20 (0.05-0.77), P=0.02], furosemide [HR 0.08 (0.01-0.76), P=0.02] and postoperative ECMO [HR 6.40 (1.65-24.77), P=0.00] were independent predictors for increased mortality. And multivariate analyses found that only postoperative ECMO [HR 9.59 (1.07-86.13), P=0.04] was independent predictors for increased mortality, whereas PNI and NRS2002 were not. CONCLUSIONS: PNI and NRS2002 was not an independent predictor for post-operative mortality, and postoperative ECMO was only independent predictors for increased mortality in this study.

Hyperbaric Oxygen Protects Against Cerebral Damage in Permanent Middle Cerebral Artery Occlusion Rats and Inhibits Autophagy Activity.

BACKGROUND: To investigate the effects of hyperbaric oxygen (HBO) on brain damage and autophagy levels in a rat model of middle cerebral artery occlusion. METHODS: Neurologic injury and infarcted areas were evaluated according to the modified neurological severity score and 2,3,5-triphenyltetrazolium chloride staining. Western blots were used to determine beclin1, caspase-3 and fodrin1 protein expression. Beclin1 protein expression (an autophagy marker), positive terminal dUTP nick-end labeling (TUNEL) staining (an apoptosis marker) and positive propidium iodide (PI) staining (a necrosis marker) were detected by immunofluorescence. RESULTS: Our results indicated that HBO could decrease the infarct volume and speed up the recovery of the neurological deficit scores in ischemic rats. Beclin1 was down-regulated after HBO treatment. HBO treatment inhibited fodrin1 protein expression and decreased the number of PI-positive cells. HBO also down-regulated caspase-3 and decreased the number of TUNEL-positive cells. CONCLUSION: Cerebral ischemia caused early neuronal death due to necrosis, followed by delayed neuronal death due to apoptosis. Consequently, autophagy might be involved in all processes of ischemia. HBO could protect the brain against ischemic injury, and the possible mechanisms might be correlated with decreased autophagy activity and decreased apoptosis and necrosis levels.

A more physiological feeding process in ICU: Intermittent infusion with semi-solid nutrients (CONSORT-compliant).

INTRODUCTION AND OBJECTIVES: The goal of this study is to determine whether the application of semi-solid nutrients could increase the efficiency of the enteral nutrition (EN), which was measured daily by administered volume of nutrition/prescribed volume of nutrition. METHODS: A total of 28 subjects were finally enrolled in the study and randomized to receive either intermittent feeding (IF) or intermittent feeding with semi-solid nutrients (IS). Three major parameters concerning EN were evaluated in this study: the daily dosage prescribed by doctor, the actual dosage received by subjects, and the acute complications such as diarrhea, vomiting, regurgitation, bowel distension, and lung infection. RESULTS: There were no statistical differences in NRS-2002, and acute gastrointestinal injury between both groups. The IS group (0.98 ±â€Š0.06, P < .01) could receive higher percentage of daily prescribed calories compared to IF (0.73 ±â€Š0.15). The total caloric intake during the first 3 days was higher in IS (2589.29 ±â€Š844.02 vs. 1685.71 ±â€Š388.00, P < .01). The incidence of feeding intolerance (FI) was lower in the IS group (2/14) compared with IF (8/14). However, semi-solid nutrients did not decrease the length of stay, lung infection, or 30-day mortality. Similarly, there was no difference in glycemic variability and stress hyperglycemia. CONCLUSIONS: In our cohort of critically ill subjects, the efficiency of the EN was increased by IS, which might be related to the improvement of FI (NCT03017079).