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BackgroundThere is still a controversy about the superiority of liposomal bupivacaine (LB) over traditional local anesthetics in postoperative analgesia after thoracic surgery. This study aims to determine the effect of LB versus bupivacaine hydrochloride (HCl) for preoperative ultrasound-guided erector spinae plane block (ESPB) on postoperative acute and chronic pain in patients undergoing video-assisted thoracoscopic lung surgery.MethodsThis multicenter, randomized, double-blind, controlled trial will include 272 adult patients scheduled for elective video-assisted thoracoscopic lung surgery. Patients will be randomly assigned, 1:1 and stratified by site, to the liposomal bupivacaine (LB) group or the bupivacaine (BUPI) HCl group. All patients will receive ultrasound-guided ESPB with either LB or bupivacaine HCl before surgery and patient-controlled intravenous analgesia (PCIA) as rescue analgesia after surgery. The numeric rating scale (NRS) score will be assessed after surgery. The primary outcome is the area under the curve of pain scores at rest for 0-72 h postoperatively. The secondary outcomes include the total amount of opioid rescue analgesics through 0-72 h postoperatively, time to the first press on the PCIA device as rescue analgesia, the area under the curve of pain scores on activity for 0-72 h postoperatively, NRS scores at rest and on activity at different time points during the 0-72 h postoperative period, Quality of Recovery 15 scores at 72 h after surgery, and NRS scores on activity on postsurgical day 14 and postsurgical 3 months. Adverse events after the surgery are followed up to the postsurgical day 7, including postoperative nausea and vomiting, fever, constipation, dizziness, headache, insomnia, itching, prolonged chest tube leakage, new-onset atrial fibrillation, severe ventricular arrhythmia, deep venous thrombosis, pulmonary embolism, pulmonary atelectasis, cardiac arrest, ileus, urinary retention, chylothorax, pneumothorax, and organ failure. Analyzes will be performed first according to the intention to treat principle and second with the per-protocol analysis.DiscussionWe hypothesize that LB for preoperative ultrasound-guided ESPB would be more effective than bupivacaine HCl in reducing postoperative pain in video-assisted thoracoscopic lung surgery. Our results will contribute to the optimization of postoperative analgesia regimens for patients undergoing video-assisted thoracoscopic lung surgery.Clinical trial registration:http://www.chictr.org.cn, identifier ChiCTR2300074852.

Denervation is closely related to many cardiovascular diseases, such as myocardial infarction, myocardial ischemia-reperfusion injury, hypertension, arrhythmia, heart failure, atherosclerosis and ventricular remodeling. Denervation affects the patients resting heart rate and responsiveness to exercise in the early stages of heart transplantation. Therefore, this article reviews the research progress of denervation in the field of cardiovascular diseases and elaborates on the mechanism of denervation in the treatment of cardiovascular disease, intending to provide new complementary treatment methods for the treatment of cardiovascular diseases.

Voltage instability, power imbalance, and unreliability are caused mainly by equipment failure in the distribution system, so it is important to accurately and quickly assess the status of distribution network equipment. However, it is challenging to detect equipment failures, the traditional XGBoost algorithm is unsuitable because some evaluation indices are incompetent to quantify. To address these issues, we propose a fast evaluation method for the state of electrical distribution equipment based on fuzzy decision-making. Firstly, key indices are selected from the multi-source equipment information. Secondly, this paper constructs the mapping between key indices and equipment status scores by combining the fuzzy iterative method and the XGBoost algorithm. Finally, the proposed assessment model is confirmed by using the distribution transformers as an example. The result shows that the proposed multi-source information assessment method can quickly and accurately determine the operation status of electrical distribution equipment, and the proposed method has better accuracy than the traditional method.

Coronavirus disease-2019 (COVID-19) has rapidly spread worldwide and causes high mortality of elderly patients. High-flow nasal cannula therapy (HFNC) is an oxygen delivery method for severely ill patients. We retrospectively analyzed the course of illness and outcomes in 110 elderly COVID-19 patients (≥65 years) treated with HFNC from 6 hospitals. 38 patients received HFNC (200 mmHg < PaO2/FiO2 ≤ 300 mmHg, early HFNC group), and 72 patients received HFNC (100 mmHg < PaO2/FiO2 ≤ 200 mmHg, late HFNC group). There were no significant differences of sequential organ failure assessment (SOFA) scores and APECH II scores between early and late HFNC group on admission. Compared with the late HFNC group, patients in the early HFNC group had a lower likelihood of developing severe acute respiratory distress syndrome (ARDS), longer time from illness onset to severe ARDS and shorter duration of viral shedding after illness onset, as well as shorter lengths of ICU and hospital stay. 24 patients died during hospitalization, of whom 22 deaths (30.6%) were in the late HFNC group and 2 (5.3%) in the early HFNC group. The present study suggested that the outcomes were better in severely ill elderly patients with COVID-19 receiving early compared to late HFNC.

Lightning is one of the main causes of voltage sags in power grid. Accurate estimation of the severity of voltage sags caused by lightning can provide a basis for developing optimal management plans and siting sensitive users. In this paper, a data-driven self-learning estimation method for the severity of voltage sags is proposed. Firstly, based on the mechanism of voltage sags caused by lightning, the parameters involved in mining are selected by the monitoring information in lightning location system and power quality monitoring system. Secondly, the influence of discretization results on the accuracy of rules is reduced, and the number of discretization intervals for different parameters is determined by using discretization evaluation indexes. Then, to solve the problem of low efficiency of mining algorithm when the grid database changes dynamically, the incremental learning-based association rule mining algorithm to continuously update the mined rules, which gives it the ability of self-learning. Finally, a weighted Euclidean distance based on the integrated assignment method is proposed to evaluate the severity of voltage sags in real scenarios. The results of the empirical analysis by monitoring data of a regional power grid and simulation data of IEEE 30-node prove that the method in this paper can accurately mine valuable rules in reality and realize the severity assessment of voltage sags of the concerned nodes.

Aim: Post‐transcriptional modifications and their specific mechanisms are the focus of research on the regulation of myocardial damage. Stress granules (SGs) can inhibit the inflammatory response by inhibiting the cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) pathway. This study investigated whether alkylation repair homologue protein 5 (ALKBH5) could affect myocardial inflammation and apoptosis during diabetic myocardial ischaemia‐reperfusion injury (IRI) through the cGAS‐STING pathway via SGs. Methods: A diabetes ischaemia‐reperfusion rat model and a high glucose hypoxia/reoxygenation cell model were established. Adeno‐associated virus (AAV) and lentivirus (LV) were used to overexpress ALKBH5, while the SG agonist arsenite (Ars) and the SG inhibitor anisomycin were used as interventions. Then, the levels of apoptosis and related indicators in the cell and rat models were measured. Results: In the in vivo experiment, compared with the normal sham group, the degree of myocardial tissue damage, creatine kinase‐MB and cardiac troponin I in serum, and myocardial apoptosis, the infarcted area of myocardium, and the level of B‐cell lymphoma 2 associated X protein, cGAS‐STING pathway and inflammatory factors in the diabetes ischaemia‐reperfusion group were significantly increased. However, the expression of SGs and the levels of ALKBH5, rat sarcoma‐GTPase‐activating protein‐binding protein 1, T‐cell intracellular antigen‐1 and Bcl2 were significantly decreased. After AAV‐ALKBH5 intervention, the degree of myocardial tissue damage, degree of myocardial apoptosis, and extent of myocardial infarction in myocardial tissue were significantly decreased. In the in vitro experiment, compared with those in the normal control group, the levels of lactate dehydrogenase, inflammation and apoptosis were significantly greater, and cell viability and the levels of ALKBH5 and SGs were decreased in the high glucose and hypoxia/reoxygenation groups. In the high glucose hypoxia/reoxygenation cell model, the degree of cell damage, inflammation, and apoptosis was greater than those in the high glucose and hypoxia/reoxygenation models, and the levels of ALKBH5 and SGs were further decreased. LV‐ALKBH5 and Ars alleviated the degree of cell damage and inhibited inflammation and cell apoptosis. The inhibition of SGs could partly reverse the protective effect of LV‐ALKBH5. The cGAS agonist G140 antagonized the inhibitory effects of the SG agonist Ars on cardiomyocyte apoptosis, inflammation and the cGAS‐STING pathway. Conclusion: Both ALKBH5 and SGs inhibited myocardial inflammation and apoptosis during diabetic myocardial ischaemia‐reperfusion. Mechanistically, ALKBH5 might inhibit the apoptosis of cardiomyocytes by promoting the expression of SGs through the cGAS‐STING pathway. [ABSTRACT FROM AUTHOR]

Lactate is not only the energy substrate of neural cells, but also an important signal molecule in brain. In modern societies, disturbed circadian rhythms pose a global challenge. Therefore, exploring the influence of circadian period on lactate and its metabolic kinetics is essential for the advancement of neuroscientific research. In the present study, the different groups of mice (L: 8:00 a.m.; D: 20:00 p.m.; SD: 20:00 p.m. with 12 h acute sleep deprivation) were infused with [3-13C] lactate through the lateral tail vein for a duration of 2 min. After 30-min lactate metabolism, the animals were euthanized and the tissues of brain and liver were obtained and extracted, and then, the [1H-13C] NMR technology was employed to investigate the kinetic information of lactate metabolism in different brain regions and liver to detect the enrichment of various metabolic kinetic information. Results revealed the fluctuating lactate concentrations in the brain throughout the day, with lower levels during light periods and higher levels during dark periods. Most metabolites displayed strong sensitivity to circadian rhythm, exhibiting significant day-night variations. Conversely, only a few metabolites showed changes after acute sleep deprivation, primarily in the temporal brain region. Interestingly, in contrast to brain lactate metabolism, liver lactate metabolism exhibited a significant increase following acute sleep deprivation. This study explored the kinetics of lactate metabolism, hinted at potential clinical implications for disorders involving circadian rhythm disturbances, and providing a new research basis for clinical exploration of brain and liver lactate metabolism. [ABSTRACT FROM AUTHOR]

Protein posttranslational modifications are important factors that mediate the fine regulation of signaling molecules. O-linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a monosaccharide modification on N-acetylglucosamine linked to the hydroxyl terminus of serine and threonine of proteins. O-GlcNAcylation is responsive to cellular stress as a reversible and posttranslational modification of nuclear, mitochondrial and cytoplasmic proteins. Mitochondrial proteins are the main targets of O-GlcNAcylation and O-GlcNAcylation is a key regulator of mitochondrial homeostasis by directly regulating the mitochondrial proteome or protein activity and function. Disruption of O-GlcNAcylation is closely related to mitochondrial dysfunction. More importantly, the O-GlcNAcylation of cardiac proteins has been proven to be protective or harmful to cardiac function. Mitochondrial homeostasis is crucial for cardiac contractile function and myocardial cell metabolism, and the imbalance of mitochondrial homeostasis plays a crucial role in the pathogenesis of cardiovascular diseases (CVDs). In this review, we will focus on the interactions between protein O-GlcNAcylation and mitochondrial homeostasis and provide insights on the role of mitochondrial protein O-GlcNAcylation in CVDs. [ABSTRACT FROM AUTHOR]

Background: Ischemic postconditioning (IPostC) has been reported as a promising method for protecting against myocardial ischemia-reperfusion (MI/R) injury. Our previous study found that the infarct-limiting effect of IPostC is abolished in the heart of diabetes whose cardiac expression of DJ-1 (also called PARK7, Parkinsonism associated deglycase) is reduced. However, the role and in particular the underlying mechanism of DJ-1 in the loss of sensitivity to IPostC-induced cardioprotection in diabetic hearts remains unclear. Methods: Streptozotocin-induced type 1 diabetic rats were subjected to MI/R injury by occluding the left anterior descending artery (LAD) and followed by reperfusion. IPostC was induced by three cycles of 10s of reperfusion and ischemia at the onset of reperfusion. AAV9-CMV-DJ-1, AAV9-CMV-C106S-DJ-1 or AAV9-DJ-1 siRNA were injected via tail vein to either over-express or knock-down DJ-1 three weeks before inducing MI/R. Results: Diabetic rats subjected to MI/R exhibited larger infarct area, more severe oxidative injury concomitant with significantly reduced cardiac DJ-1 expression and increased PTEN expression as compared to non-diabetic rats. AAV9-mediated cardiac DJ-1 overexpression, but not the cardiac overexpression of DJ-1 mutant C106S, restored IPostC-induced cardioprotection and this effect was accompanied by increased cytoplasmic DJ-1 translocation toward nuclear and mitochondrial, reduced PTEN expression, and increased Nrf-2/HO-1 transcription. Our further study showed that AAV9-mediated targeted DJ-1 gene knockdown aggravated MI/R injury in diabetic hearts, and this exacerbation of MI/R injury was partially reversed by IPostC in the presence of PTEN inhibition or Nrf-2 activation. Conclusions: These findings suggest that DJ-1 preserves the cardioprotective effect of IPostC against MI/R injury in diabetic rats through nuclear and mitochondrial DJ-1 translocation and that inhibition of cardiac PTEN and activation of Nrf-2/HO-1 may represent the major downstream mechanisms whereby DJ-1 preserves the cardioprotective effect of IPostC in diabetes. [ABSTRACT FROM AUTHOR]