Over the past 10 years, the crisis of sepsis has remained a great challenge. According to data from 2016, the sepsis-related mortality rate remains high. In addition, sepsis consumes extensive medical resources in intensive care units, and anti-inflammatory agents fail to improve sepsis-associated hyperinflammation and symptoms of immunosuppression. The specific immune mechanism of sepsis remains to be elucidated. Reactive oxygen species (ROS) are triggered by energy metabolism and respiratory dysfunction in sepsis, which not only cause oxidative damage to tissues and organelles, but also directly and indirectly promote NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. NLRP3 inflammasomes enlarge the inflammatory response and trigger apoptosis of immune cells to exacerbate sepsis progression. Inhibiting the negative effects of ROS and NLRP3 inflammasomes therefore provides the possibility of reversing the excessive inflammation during sepsis. In this review, we describe the interaction of ROS and NLRP3 inflammasomes during sepsis, provide prevention strategies, and identify fields that need further study.

Worldwide, 80% of patients who undergo surgery receive opioid analgesics as the fundamental agent for pain relief. However, the irrational use of opioids leads to excessive drug dependence and drug abuse, resulting in an increased mortality rate and huge economic loss. The crisis of opioid overuse remains a great challenge. In this review, we summarize several key factors in opioid abuse, including race, region, income, genetic factors, age and gender, smoking and alcohol abuse, history of chronic pain and analgesic drug abuse, surgery, neuropsychiatric illness, depression and antidepressant use, human factors, national policies, hospital regulations, and health insurance under treatment of pain. Furthermore, we present several prevention strategies, such as perioperative measures, opioid substitutes, treatment of the primary illness, emotional regulation, use of opioid antagonists, efforts of the state, hospitals, doctors and pharmacy benefit managers, gene therapy, and vaccines. Greater understanding and better assessment are required of the risks associated with opioid abuse to ensure the safety and analgesic effects of pain treatment after surgery.

Objective: To investigate the effect of smoking cessation before surgery on postoperative pain and analgesic consumption after thoracoscopic radical resection of lung cancer in elderly patients with high nicotine dependence. Methods: A total of 107 male patients, ages 60 to 70 years, undergoing elective thoracoscopic radical lung cancer surgery from July 2017 to July 2018 were enrolled into 3 groups: group A (highly nicotine-dependent and discontinued smoking 3 weeks before surgery, n = 38), and group C (nonsmokers, n = 33). Postoperative sufentanil consumption, visual analog scale (VAS) pain scores at rest and during cough, rescue analgesia, opioid-related adverse events, and patient satisfaction were assessed from 0 to 48 h postoperatively. Results: Patient characteristics were comparable among the 3 groups. Sufentanil consumption and VAS pain scores from postoperative 0 to 48 h were significantly higher in groups A and B than in group C. In addition, group B had lower sufentanil consumption and pain scores than group A. No differences in the need for rescue analgesia, patient satisfaction, or occurrence of postoperative adverse events, including nausea, vomiting, respiratory depression, and oversedation, were observed among the 3 groups. Conclusion: Compared with nonsmokers, highly nicotine-dependent male patients who were deprived of cigarettes experienced more severe pain and required treatment with more sufentanil after thoracoscopic radical lung cancer surgery. Moreover, preoperative smoking cessation at least 3 weeks before surgery led to better postoperative pain outcomes than smoking cessation within 3 weeks of surgery.

Acute type A aortic dissection (ATAAD) is a lethal pathological process within the aorta with high mortality and morbidity. T lymphocytes are perturbed and implicated in the clinical outcome of ATAAD, but the exact characteristics of T cell phenotype and its underlying mechanisms in ATAAD remain poorly understood. Here we report that CD4⁺ T cells from ATAAD patients presented with a hypofunctional phenotype that was correlated with poor outcomes. Whole transcriptome profiles showed that ferroptosis and lipid binding pathways were enriched in CD4⁺ T cells. Inhibiting ferroptosis or reducing intrinsic reactive oxygen species limited CD4⁺ T cell dysfunction. Mechanistically, CD36 was elevated in CD4⁺ T cells, whose blockade effectively alleviated palmitic acid-induced ferroptosis and CD4⁺ T cell hypofunction. Therefore, targeting the CD36-ferroptosis pathway to restore the functions of CD4⁺ T cells is a promising therapeutic strategy to improve clinical outcomes in ATAAD patients.

Background: The spinal cord expresses brain-derived neurotrophic factor precursor (proBDNF) and its receptor pan neurotrophin receptor 75 (p75^NTR). However, the role of spinal proBDNF signaling in the pathogenesis of inflammatory pain remains unknown. Methods: Rats were locally injected with complete Freund’s adjuvant (CFA) to induce inflammatory pain. The proBDNF signal expression was detected by double-labeled immunofluorescence. ProBDNF protein, p75^NTR extracellular domain (p75^NTR-ECD), or monoclonal anti-proBDNF (McAb-proB) were administrated by intrathecal injection to investigate their effects on pain behavior. Paw withdrawal thermal latency (PWL) and paw withdrawal mechanical threshold (PWT) were performed to evaluate pain behavior. Immunoblotting, immunohistochemistry, and immunofluorescence were used to assess inflammation-induced biochemical changes. Results: CFA induced a rapid increase in proBDNF in the ipsilateral spinal cord, and immunofluorescence revealed that CFA-enhanced proBDNF was expressed in NeuN positive neurons and GFAP positive astrocytes. The administration of furin cleavage-resistant proBDNF via intrathecal injection (I.t.) significantly decreased the PWT and PWL, whereas McAb-proB by I.t. alleviated CFA-induced pain-like hypersensitivity in rats. Meanwhile, CFA administration triggered the activation of p75^NTR and its downstream signaling extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor (NF)-kappaB p65 in the spinal cord. I.t. administration of p75^NTR-ECD suppressed CFA-induced pain and neuroinflammation, including the expression of p-ERK1/2, p-p65, and the gene expression of tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6). Conclusion: Our study reveals that the activated proBDNF/p75^NTRsignaling in the spinal cord contributes to the development of CFA-induced inflammatory pain. McAb-proB and p75^NTR-ECD appear to be promising therapeutic agents for inflammatory pain.