Nuclear receptor subfamily 4, group A, member 1 (NR4A1) can aggravate ischaemia‐reperfusion (I/R) injury in the heart, kidney and brain. Thus, the present study aimed to unravel the role of NR4A1 on hepatic I/R injury. For this purpose, the mouse hepatic I/R model and H/R‐exposed mouse hepatocytes model were established to stimulate the hepatic and hepatocellular damage. Then, the levels of ALT and AST as well as TNF‐α and IL‐1β expression were measured in the mouse serum and supernatant of hepatocyte s, respectively. Thereafter, we quantified the levels of NR4A1, CYR61, NF‐kB p65 and TGFβ1 under pathological conditions, and their interactions were analysed using ChIP and dual‐luciferase reporter gene assays. The in vivo and in vitro effects of NR4A1, CYR61, NF‐kB p65 and TGFβ1 on I/R‐induced hepatic and H/R‐induced hepatocellular damage were evaluated using gain‐ and loss‐of‐function approaches. NR4A1 was up‐regulated in the hepatic tissues of I/R‐operated mice and in H/R‐treated hepatocytes. Silencing NR4A1 relieved the I/R‐induced hepatic injury, as supported by suppression of ALT and AST as well as TNF‐α and IL‐1β. Meanwhile, NR4A1 knockdown attenuated the H/R‐induced hepatocellular damage by inhibiting the apoptosis of hepatocyte s. Moreover, we also found that NR4A1 up‐regulated the expression of CYR61 which resulted in the activation of the NF‐κB signalling pathway, thereby enhancing the transcription of TGFβ1, which was validated to be the mechanism underlying the contributory role of NR4A1 in hepatic I/R injury. Taken together, NR4A1 silencing reduced the expression of CYR61/NF‐κB/TGFβ1, thereby relieving the hepatic I/R injury.

Objective. To explore the related risk factors of postoperative delirium (POD) after hip or knee arthroplasty in elderly orthopedic patients and the predictive value of related risk factors. Material and Methods. In total, 309 patients (≥60 years) who received knee and hip arthroplasty between January 2017 and May 2020 were consecutively selected into the POD and nonpostoperative delirium (NPOD) groups. Group bias was eliminated through propensity score matching. Univariate and multivariable logistic analysis was used to determine the risk factors for POD. The nomogram was made by R. Results. 58 patients were included in each group after propensity score matching; multivariable analysis demonstrated that LDH (OR = 4.364, P = 0.017), CHE (OR = 4.640, P = 0.004), Cystatin C (OR = 5.283, P = 0.006), arrhythmia (OR = 5.253, P = 0.002), and operation duration (OR = 1.017, P = 0.050) were independent risk factors of POD. LDH, CHE, Cystatin C, and arrhythmia were used to construct a nomogram to predict the POD. The nomogram was well calibrated and had moderate discriminative ability (AUC = 0.821, 95% CI: 0.760~0.883). Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusions. Our study revealed that arrhythmia, operation duration, the increase of lactate dehydrogenase and Cystatin C, and the decrease of cholinesterase were reliable factors for predicting postoperative delirium after elderly hip and knee arthroplasty. Meanwhile, the nomogram we developed can assist the clinician to filtrate potential patients with postoperative delirium.

Background.: Liver ischemia/reperfusion injury (I/RI) is characterized by inflammatory actions. Understanding the mechanistic insights underpinning inflammation is critical to developing treatment strategies. In this study, we illustrated the mechanistic insights of transcription factor Yin-Yang 1 (YY1)-mediated microRNA (miR)-181a-5p/estrogen receptor alpha (ESR1)/epidermal growth factor receptor 2 (ERBB2) axis in liver I/RI. Methods.: First, we established liver I/RI models in mice and hypoxia-reperfusion (H/R) cell models in mouse hepatocytes (AML12). Subsequently, the expression of YY1, miR-181a-5p, and ESR1 was determined in the 2 models. I/RI mouse models were further injected with lentivirus carrying oe-YY1‚ and H/R-exposed AML12 cells were subjected to a series of inhibitors, mimics, and shRNAs to validate the mechanisms of YY1 in controlling miR-181a-5p and ESR1 in liver I/RI. Results.: Upregulated expression of miR-181a-5p and downregulated expression of YY1 were identified in the liver tissues of liver I/RI mice and H/R-exposed hepatocytes. Moreover, overexpression of YY1 inhibited the miR-181a-5p expression and thus repressed the H/R-induced hepatocyte apoptosis and inflammation. ESR1 was further validated as a target gene of miR-181a-5p and could be negatively regulated by miR-181a-5p. miR-181a-5p inhibition elevated ESR1 expression, which consequently enhanced the ERBB2 expression and reduced H/R-induced hepatocyte apoptosis and inflammation. Conclusions.: Overall, these findings highlighted that YY1 repressed the miR-181a-5p expression and stimulated ESR1-mediated activation of ERBB2, thereby ameliorating liver I/RI. This study provides insight into the development of novel targets for liver I/RI.

Objectives: This study aimed to compare the analgesic effects of continuous femoral nerve block (FNB), femoral triangle block (FTB), and adductor canal block (ACB) following total knee arthroplasty (TKA). The goal was to identify the most effective nerve block technique among these. Methods: Patients undergoing TKA were randomly assigned to 1 of 3 groups: FNB, FTB, or ACB. Nerve blocks were administered preoperatively, with catheters placed for patient-controlled nerve analgesia (PCNA). The primary end point was the Numeric Rating Scale (NRS) score at movement at 24 hours postsurgery. Secondary end points included NRS scores at rest and movement, quadriceps strength, Timed Up and Go (TUG) test performance, range of motion, effective PCNA utilization, and opioid consumption at various postsurgery time points. Results: Of the 94 valid data sets analyzed (FNB: 31, FTB: 31, ACB: 32), significant differences were observed in the primary end point (H=7.003, P=0.03). Post hoc analysis with Bonferroni correction showed that the FNB group had a significantly lower median pain score (3 [2 to 4]) compared with the ACB group (4 [3 to 5], Bonferroni-adjusted P=0.03). Regarding secondary end points, both the FNB and FTB groups had significantly lower NRS scores than the ACB group at various time points after surgery. Quadriceps strength and TUG completion were better in the FTB and ACB groups. There were no statistically significant differences among the groups for the other end points. Discussion: Continuous FTB provides postoperative analgesia comparable to FNB but with the advantage of significantly less impact on quadriceps muscle strength, a benefit not seen with FNB. Both FTB and ACB are effective in preserving quadriceps strength postoperatively.

To explore the mechanism of Maresin1 in reducing cerebral ischemia-reperfusion injury. Male C57BL/6 mice were randomly divided (n=5 in each group), and focal middle cerebral artery occlusion (MCAO) model was used to simulate cerebral ischemia/reperfusion injury. TTC and the Longa score were used to detect the degree of neurological deficits. Western blot was used to detect the expression levels of GSDME, GSDME-N, caspase-3 and cleaved caspase-3 in cerebral ischemic penumbra tissue, and immunofluorescence was used to detect the expression levels of GSDME-N. The mRNA expression levels of GSDME and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were detected by RT-PCR. Compared with sham group, GSDME mRNA levels in MCAO group were significantly increased at 12h and 24h after reperfusion, and GSDME and GSDME-N significantly increased at 6-48h after reperfusion. Compared with sham group, the percentage of infarct size, the Longa score, the mRNA expression levels of IL-1β, IL-6 and TNF-α, and GSDME, GSDME-N, caspase-3 and cleaved caspase-3 in MCAO group was significantly increased. Then, the percentage of infarct size and the Longa score significantly decreased after MaR1 administration, the mRNA expression levels of IL-1β and IL-6 downregulated, and GSDME, GSDME-N, caspase-3 and cleaved caspase-3 were also reduced. After administration of Z-DEVD-FMK(ZDF), the expression of caspase-3, cleaved caspase-3 and GSDME-N was decreased, which in MCAO+MaR1+ZDF group was not statistically significant compared with MCAO+ ZDF group. Maresin1 alleviates cerebral ischemia/reperfusion injury by inhibiting pyroptosis mediated by caspase-3/GSDME pathway and alleviating neuroinflammation.