Metabolites have recently been found to be involved in significant biological regulation and changes. Itaconate, an important intermediate metabolite isolated from the tricarboxylic acid cycle, is derived from cis-aconitate decarboxylation mediated by immune response gene 1 in mitochondrial matrix. Itaconate has emerged as a key autocrine regulatory component involved in the development and progression of inflammation and immunity. It could directly modify cysteine sites on functional substrate proteins which related to inflammasome, signal transduction, transcription, and cell death. Itaconate can be a connector among immunity, metabolism, and inflammation, which is of great significance for further understanding the mechanism of cellular immune metabolism. And it could be the potential choice for the treatment of inflammation and immune-related diseases. This study is a systematic review of the potential mechanisms of metabolite associated with different pathology conditions. We briefly summarize the structural characteristics and classical pathways of itaconate and its derivatives, with special emphasis on its promising role in future clinical application, in order to provide theoretical basis for future research and treatment intervention.

The bioactive lipid lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL), originates from the cleavage of phosphatidylcholine by phospholipase A2 (PLA2) and is catabolized to other substances by different enzymatic pathways. LPC exerts pleiotropic effects mediated by its receptors, G protein-coupled signaling receptors, Toll-like receptors, and ion channels to activate several second messengers. Lysophosphatidylcholine (LPC) is increasingly considered a key marker/factor positively in pathological states, especially inflammation and atherosclerosis development. Current studies have indicated that the injury of nervous tissues promotes oxidative stress and lipid peroxidation, as well as excessive accumulation of LPC, enhancing the membrane hyperexcitability to induce chronic pain, which may be recognized as one of the hallmarks of chronic pain. However, findings from lipidomic studies of LPC have been lacking in the context of chronic pain. In this review, we focus in some detail on LPC sources, biochemical pathways, and the signal-transduction system. Moreover, we outline the detection methods of LPC for accurate analysis of each individual LPC species and reveal the pathophysiological implication of LPC in chronic pain, which makes it an interesting target for biomarkers and the development of medicine regarding chronic pain.

Nerve injury–induced changes of gene expression in dorsal root ganglion (DRG) are critical for neuropathic pain genesis. However, how these changes occur remains elusive. Here we report the down-regulation of zinc finger protein 382 (ZNF382) in injured DRG neurons after nerve injury. Rescuing this down-regulation attenuates nociceptive hypersensitivity. Conversely, mimicking this down-regulation produces neuropathic pain symptoms, which are alleviated by C-X-C motif chemokine 13 (CXCL13) knockdown or its receptor CXCR5 knockout. Mechanistically, an identified cis-acting silencer at distal upstream of the Cxcl13 promoter suppresses Cxcl13 transcription via binding to ZNF382. Blocking this binding or genetically deleting this silencer abolishes the ZNF382 suppression on Cxcl13 transcription and impairs ZNF382-induced antinociception. Moreover, ZNF382 down-regulation disrupts the repressive epigenetic complex containing histone deacetylase 1 and SET domain bifurcated 1 at the silencer-promoter loop, resulting in Cxcl13 transcriptional activation. Thus, ZNF382 down-regulation is required for neuropathic pain likely through silencer-based epigenetic disinhibition of CXCL13, a key neuropathic pain player, in DRG neurons.

Perioperative allogenic transfusion is required in almost 50% of patients undergoing cardiac surgery and is associated with higher risk of mortality and morbidity (Xue et al., Lancet 387:1905, 2016; Ferraris et al., Ann Thorac Surg 91:944–82, 2011). Acute normovolemic hemodilution (ANH) is recommended as a potential strategy during cardiac surgery, but the blood conservation effect and the degree of ANH was still controversial. There is also an increasing concern about the improved outcomes associated with ANH. Therefore, a better understanding of the effect of mild volume ANH during cardiac surgery is urgently needed. This retrospective study included 2058 patients who underwent cardiac surgery between 2010 and 2015. The study population was split into two groups (with and without mild volume ANH). Propensity score adjustment analysis was applied. We reported the association between the use of mild volume ANH and perioperative outcomes. A total of 1289 patients were identified. ANH was performed in 358 patients, and the remaining 931 patients did not receive any ANH. Five hundred of the total patients (38.8%) received perioperative RBC transfusions, 10% (129/1289) of patients received platelet, and 56.4% (727/1289) of patients received fresh frozen plasma transfusions. Mild volume ANH administration was significantly associated with decreased intraoperative RBC transfuse rate (8.5% vs. 14.4%; p = 0.013), number of RBC units (p = 0.019), and decreased postoperative pulmonary infection (6.8 vs. 11.3%; p = 0.036) during cardiac surgery. However, there was no significant difference regarding intraoperative fresh frozen plasma (FFP) and platelet concentrate transfusions, as well as postoperative and total perioperative allogeneic transfusions. Furthermore, there was no significant difference regarding postoperative outcomes including mortality, prolonged wound healing, stroke, atrial fibrillation, reoperation for postoperative bleeding and acute kidney injury. There was also no difference in postoperative ventilation time, length of ICU and hospital stay. Based on the 5-year experience of mild volume ANH in cardiac surgeries with CPB in our large retrospective cohort, mild volume ANH was associated with decreased intraoperative RBC transfusion and postoperative pulmonary infection in Chinese patients undergoing cardiac surgery. However, there was no significant difference regarding postoperative and total perioperative allogeneic transfusions.

Background: Postoperative pulmonary complications (PPCs) and hypoxaemia are associated with morbidity and mortality. We aimed to evaluate the feasibility and efficacy of lung ultrasound (LUS) to diagnose PPCs in patients suffering from hypoxaemia after general anaesthesia and compare the results to those of thoracic computed tomography (CT).Methods: Adult patients who received general anaesthesia and suffered from hypoxaemia in the postanaesthesia care unit (PACU) were analysed. Hypoxaemia was defined as an oxygen saturation measured by pulse oximetry (SPO₂) less than 92% for more than 30 s under ambient air conditions. LUS was performed by two trained anaesthesiologists once hypoxaemia occurred. After LUS examination, each patient was transported to the radiology department for thoracic CT scan within 1 h before returning to the ward.Results: From January 2019 to May 2019, 113 patients (61 men) undergoing abdominal surgery (45 patients, 39.8%), video-assisted thoracic surgery (31 patients, 27.4%), major orthopaedic surgery (17 patients, 15.0%), neurosurgery (10 patients, 8.8%) or other surgery (10 patients, 8.8%) were included. CT diagnosed 327 of 1356 lung zones as atelectasis, while LUS revealed atelectasis in 311 of the CT-confirmed zones. Pneumothorax was detected by CT scan in 75 quadrants, 72 of which were detected by LUS. Pleural effusion was diagnosed in 144 zones on CT scan, and LUS detected 131 of these zones. LUS was reliable in diagnosing atelectasis (sensitivity 98.0%, specificity 96.7% and diagnostic accuracy 97.2%), pneumothorax (sensitivity 90.0%, specificity 98.9% and diagnostic accuracy 96.7%) and pleural effusion (sensitivity 92.9%, specificity 96.0% and diagnostic accuracy 95.1%).Conclusions: Lung ultrasound is feasible, efficient and accurate in diagnosing different aetiologies of postoperative hypoxia in healthy-weight patients in the PACU.Trial registration: Current Controlled TrialsNCT03802175, 2018/12/05,www.ClinicalTrials.gov