BackgroundTo investigate the incidence and related risk factors of delirium in elderly patients with hip fracture.MethodsThis is a retrospective study, performed in a medical center from October 2014 to February 2017, which enrolled all subjects aged over 65 years who were admitted for hip surgeries (hip arthroplasty, proximal femoral nail fixation). Univariate and multivariate logistic analysis was used to determine the incidence and risk factors of delirium. Delirium was assessed according to the Confusion Assessment Method (CAM).ResultsOverall, 19.29% of total 306 patients (mean age 81.9 ± 5.4 years) were identified as delirium. The delirium was significantly associated (p < 0.05) with the factors of age, hospitalization, diabetes, preoperative hematocrit (HCT), perioperative protein consumption, transfusion volume, preoperative leukocyte level, albumin level, American Society of Anesthesiologists (NYHA) classification, American Society of Anesthesiologists (ASA) classification, blood loss, coronary heart disease, and cerebral infarction. Multivariate analysis of the variables confirmed that age (> 75 years old), diabetes, and ASA classification (> 2 level) are the independent risk factors of postoperative delirium (POD). In addition, patients in delirium had prolonged hospitalization and high perioperative albumin infusion.ConclusionThe elderly patients over the age of 75 years with the history of diabetes or ASA classification > 2 level were at higher risk of POD. Delirium is an important postoperative complication, which had prolonged hospitalization and high perioperative albumin infusion.Level of evidence: III

Oxidative stress induced by long-term glucocorticoid (GC) use weakens the repair capacity of bone tissue. Nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase (NOX) is a superoxide-generating enzyme that plays an important role in regulating bone metabolism. To clarify the role of nonphagocytic NOX isoforms in osteoblast reactive oxygen species (ROS) generation and apoptosis, dexamethasone was used to establish a high-dose GC environment in vitro. A dose-dependent increase in intracellular ROS generation was demonstrated, which was accompanied by increased osteoblastic MC3T3-E1 cell apoptosis. Addition of the ROS inhibitor NAC (N-acetyl-L-cysteine) or NOX inhibitor DPI (diphenyleneiodonium) reversed this effect, indicating that NOX-derived ROS can induce osteoblast apoptosis under high-dose dexamethasone stimulation. NOX1, NOX2, and NOX4 are NOX homologs recently identified in bone tissue. To clarify the NOX isoforms that play a role in osteoblast ROS generation, Nox1, Nox2, and Nox4 mRNA expression and NOX2 and NOX4 protein expression were analyzed. Nox1 and Nox4 mRNA expression was elevated in a dose-dependent manner after culture in 100 nM, 250 nM, 500 nM, or 1000 nM dexamethasone, and the increased expression of NOX1 mRNA was more significant compared with NOX4 mRNA. Small interfering RNAs (siRNAs) were used to confirm the role of NOX1 and NOX4 in ROS generation. To clarify the signaling pathway in ROS-induced osteoblast apoptosis, mitogen-activated protein kinase (MAPK) signaling molecules were analyzed. Phosphorylated ASK1 and p38 levels were significantly higher in the 1000 nM dexamethasone group, which NAC or DPI markedly attenuated. However, the total mRNA and protein levels of ASK1 and p38 between the dexamethasone group and control were not significantly different. This is related to ROS regulating the posttranslational modification of ASK1 and p38 in MC3T3-E1 cell apoptosis. Altogether, NOX1- and NOX4-derived ROS plays a pivotal role in high-dose dexamethasone-induced preosteoblast apoptosis by increasing phosphorylated ASK1 and p38 and may be an important mechanism in steroid-induced avascular necrosis of the femoral head (SANFH).

Lung ischemia/reperfusion (I/R) injury (LIRI) is a common complication after lung transplantation, embolism, and trauma. N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of I/R injury. However, there are no or few reports of m6A-related regulators in LIRI till now. In this text, dysregulated genes in lung tissues of LIRI rats versus the sham group were identified by RNA sequencing (RNA-seq). RNA-seq outcomes revealed that only YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) were differentially expressed in the LIRI versus sham group among 20 m6A-related regulators. Next, the functions and molecular mechanisms of YTHDF3 and IGF2BP2 in LIRI were investigated in a hypoxia/reoxygenation-induced BEAS-2B cell injury model in vitro . Results showed that YTHDF3 or IGF2BP2 knockdown attenuated hypoxia/reoxygenation-mediated inhibitory effects on cell survival and cell cycle progression and inhibited hypoxia/reoxygenation-induced cell apoptosis and pro-inflammatory cytokine secretion in BEAS-2B cells. Genes that could be directly regulated by YTHDF3 or IGF2BP2 were identified based on prior experimental data and bioinformatics analysis. Moreover, multiple potential downstream pathways of YTHDF3 and IGF2BP2 were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis of the above-mentioned genes. Among these potential pathways, we demonstrated that YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-κB pathways in BEAS-2B cells. In conclusion, YTHDF3 or IGF2BP2 knockdown weakened hypoxia/reoxygenation-induced human lung bronchial epithelial cell injury by inactivating p38, AKT, ERK1/2, and NF-κB pathways.

Cell–material interactions during early osseointegration of the bone–implant interface are critical and involve crosstalk between osteoblasts and osteoclasts. The surface properties of titanium implants also play a critical role in cell–material interactions. In this study, femtosecond laser treatment and sandblasting were used to alter the surface morphology, roughness and wettability of a titanium alloy. Osteoblasts and osteoclasts were then cultured on the resulting titanium alloy disks. Four disk groups were tested: a polished titanium alloy (pTi) control; a hydrophilic micro-dislocation titanium alloy (sandblasted Ti (STi)); a hydrophobic nano-mastoid Ti alloy (femtosecond laser-treated Ti (FTi)); and a hydrophilic hierarchical hybrid micro-/nanostructured Ti alloy [femtosecond laser-treated and sandblasted Ti (FSTi)]. The titanium surface treated by the femtosecond laser and sandblasting showed higher biomineralization activity and lower cytotoxicity in simulated body fluid and lactate dehydrogenase assays. Compared to the control surface, the multifunctional titanium surface induced a better cellular response in terms of proliferation, differentiation, mineralization and collagen secretion. Further investigation of macrophage polarization revealed that increased anti-inflammatory factor secretion and decreased proinflammatory factor secretion occurred in the early response of macrophages. Based on the above results, the synergistic effect of the surface properties produced an excellent cellular response at the bone–implant interface, which was mainly reflected by the promotion of early ossteointegration and macrophage polarization.