Neuropathic pain (NP) is a clinical symptom that accompanies many diseases. We investigated the effect of receptor-interacting protein kinase 3 (RIP3)-regulated necroptosis on NP and explored its relationship with microglia, in order to provide a theoretical basis for further research and provide new insights into the treatment of NP. In this study, the spared nerve injury (SNI) model was used along with intervention with necrostatin and the inhibitor of necroptosis necrostatin-1 (Nec-1). Pain behavior tests were performed 1 and 3 days before the nerve injury (or sham) operation, and on days 1, 3, 5, 7, 10, and 14 after the operation. The spinal cord tissues were collected for detection of RIP3 expression and distribution, changes in the number of microglia cells, activation of necroptosis, and the level of proinflammatory factors. Collected spinal cord tissues were analyzed using western blot, immunohistochemistry, immunofluorescence, immunoprecipitation assays, and ELISA, respectively. We found that, compared with the sham group, the expression of RIP3 protein in the spinal cord of rats in the SNI group increased from 3 to 14 days after surgery. Immunofluorescence staining showed that RIP3 was coexpressed with the microglia and the number of microglia increased significantly in the SNI model group. The results of immunoprecipitation assays suggested that a RIP3-mediated necroptosis pathway promotes NP. After treatment with Nec-1, the expression of RIP3 protein and the number of microglia were significantly reduced, and the expression levels of TNF-a, IL-1b, and IL-6 in spinal dorsal horns were significantly decreased. These results indicate that RIP3 promotes necroptosis to increase the occurrence of NP via microglia.Neuropathic pain (NP) refers to pain caused by damage or disease to the somatic sensory system. Studies have shown that its clinical prevalence can be as high as 10% and that it severely affects the quality of life of patients [1]. The molecular biological mechanism of NP is complex and the pathogenesis is still unclear, but the current research indicates that proinflammatory and inflammatory factors, cell apoptosis, receptors, ion channel changes, peripheral sensitization, and central sensitization are all involved in the generation and maintenance of NP [2][3][4][5]. Among these factors, apoptosis and inflammation of spinal cord cells play especially important roles in the generation and maintenance of NP.

Background The incidence of postoperative delirium (POD) is high in elderly patients with one-lung ventilation, which is mostly related to the impairment of cerebral oxygen supply/demand balance during operation. (Surgical) stress can cause changes to normal physiological function and increase oxygen supply to the brain. When cerebral oxygen supply/demand is unbalanced, other organs may have already suffered from hypoperfusion or even hypoxic damages leading to increased release of inflammatory factors. Regional saturation of cerebral oxygenation (rScO2) monitoring can noninvasively monitor the variation of regional cerebral oxygen supply/demand balance in real time, and it has a good correlation with the occurrence of POD. S-100β is one of the markers commonly used to predict and diagnose POD, and lactate is one of the important indicators for the quality of tissue perfusion. The study explores whether the goal-directed therapy based on rScO2 monitoring can reduce perioperative inflammatory factor levels and POD incidence in elderly patients with one-lung ventilation and improve tissue perfusion. Methods The study is registered on Chinese Clinical Trial Registry (ChiCTR2100054888). A total of 159 patients scheduled for thoracoscopic lobectomy under general anesthesia were divided into the control group (n = 81) and the goal-directed therapy group (GDT group, n = 78). On the basis of the conventional management in the control group, the GDT group applied goal-directed rScO2 monitoring to maintain rScO2 at ±20% baseline level during one-lung ventilation. The levels of interleukin-1β, interleukin-6, tumor necrosis factor-α, and lactate; the intensity of postoperative pain; and the incidence of POD before anesthesia (T1), at the end of operation (T2), on day 1 after operation (T3), on day 3 after operation (T4), and on day 7 after operation or before discharge (T5) were compared respectively between the two groups. Results The incidence of POD at T3 and the awakening time in the GDT group were lower than those in the control group (P < 0.05). During T2 to T4, the levels of inflammatory factors and lactate concentration in the control group were higher than those in the GDT group (P < 0.05). During T3 to T4, the levels of C-reactive protein and lactate in the control group were higher than those in the GDT group (P < 0.05). During T2 to T3, the levels of S-100β in the control group were higher than those in the GDT group (P < 0.05). The levels of inflammatory factors and lactate concentration in both groups during T2 to T4 were higher than those at T1 and T5 (P < 0.05), and there was no statistical difference at T1 versus T5 (P > 0.05). There was no significant difference in postoperative pain intensity, the incidence of agitation during awakening, and postoperative hospital stays between the two groups. Conclusion Goal-directed therapy based on rScO2 monitoring can reduce perioperative inflammatory factor levels, postoperative delirium incidence, and postoperative awakening time and improve tissue perfusion in elderly patients with one-lung ventilation. Trial registration The Chinese Clinical Trial Registry ChiCTR2100054888. Registered on 28 December 2021

Background The study aimed at exploring an optimal temperature model of forced air warming during the first hour after induction and intraoperation to prevent hyperthermia for elderly patients undergoing laparoscopic abdominal surgery. Methods There were 218 patients that were randomly divided into 3 groups warmed with a forced-air warmer during surgery: Group L (intraoperative warming set to 38 °C, n = 63), Group H (intraoperative warming set to 42 °C, n = 65) and Group LH (intraoperative warming set to 42 °C for the first hour then set to 38 °C, n = 65). Core temperature in the preoperative room and PACU was measured by a tympanic membrane thermometer and in the operation room, a nasopharyngeal temperature probe was recorded. The rate of perioperative hypothermia, defined as a reduction in body temperature to < 36 °C was recorded as the primary outcome. Intraoperative anesthetic dosage, recovery time, adverse events, thermal comfort and satisfaction score were measured as secondary outcome. Results The incidence of intraoperative and postoperative hypothermia was significantly lower in Group LH and Group H than Group L (18.75 and 15.62% vs 44.44%, P<0.001; 4.69 and 4.69% vs 20.63%, P<.05). Anesthetic dosage of rocuronium was lower in Group L than other two groups, with the opposite result of recovery time. The number of patients with shivering was higher in Group L but sweating was higher in Group H. Both of the thermal comfort and satisfaction score was highest in Group LH. Conclusion A temperature pattern of forced air warming set at 42 °C during the first hour after anesthesia induction and maintained with 38 °C was a suitable choice for elderly patients undergoing laparoscopic abdominal surgery lasting for more than 120 min. Trial registration Chictr.org.cn ChiCTR-2,100,053,211.

Background: Endogenously produced glucocorticoids exhibit immunomodulating properties and are of pivotal importance for sepsis outcome. Uncontrolled activation of the immune-adrenal crosstalk increases the risk of sepsis-related death. Triggering receptor expressed on myeloid cells-2 (TREM2) is richly expressed on macrophages and has been demonstrated to improve outcome of sepsis by enhancing elimination of pathogens. However, the role and mode of action of macrophage TREM2 on adrenocortical steroidogenesis remains unclear in septic shock.Methods: The acute septic shock model was established by intraperitoneally challenging wild-type (WT) and TREM2 knock-out (Trem2-/-) mice with lipopolysaccharide (30 mg/kg). The mice were assessed for TREM2 expression and local inflammation in adrenal gland and synthesis of corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in vivo. Bone marrow-derived macrophages or macrophage-derived exosomes were isolated from WT and Trem2-/- mice and co-cultured with adrenocortical cells. The expression of steroidogenic enzymes and corticosterone production were assessed.Results: Genetic deficiency of TREM2 caused significantly higher corticosterone levels (326.6 ± 73.0 ng/ml in Trem2-/- mice vs. 151.1 ± 58.9 ng/ml in WT mice; p < 0.001) at the early stage of LPS-induced septic shock. While TREM2 deficiency neither increased CRH and ACTH, nor exacerbated the inflammation in adrenocortical tissue during septic shock. Ex vivo study revealed that Trem2-/- macrophages significantly promoted the expression of steroidogenic enzymes and increased production of corticosterone (27.73 ± 1.78 ng/ml in Trem2-/- mice vs. 22.96 ± 1.94 ng/ml in W T mice; p < 0.01). Furthermore, Trem2-/- macrophage-derived exosomes were able to mimic Trem2-/- macrophages in enhancing adrenocortical steroidogenesis. Conclusions: At the early stage of lipopolysaccharide-induced septic shock, macrophage TREM2 inhibited the steroid synthesis and corticosterone production in adrenocortical cells, which may be partially associated with macrophage-derived exosomes.