Objective:To assess the clinical outcome of the novel computer assisted reduction malarplasty using angled double L-shaped osteotomies.Methods:Retrospective analysis of the 35 female patients who received reduction malarplasty surgery during June 2014 to April 2019 was conducted. Patients were divided into the conventional surgery group (9 cases) and the computer assisted surgery group (26 cases) based on their personal will. For the conventional surgery group, the zygomatic arch was repositioned inwardly after L-shaped osteotomy, and was rigidly fixed with miniplates and screws. The computer assisted reduction malarplasty was as follows: computer assisted angled double L-shaped osteotomies with surgical guide was performed intraorally, and the pre-bent titanium was used to setback the resected zygoma bone, which was then fixed with titanium miniplates and screws. Operation time, patients’ satisfaction (3-month follow-up) and postoperative complications (asymmetry and bone nonunion) were recorded and assessed. CT scans were performed to compare the preoperative design and 3-month postoperative follow-up for the computer assisted patient group. For statistical analysis, independent sample t test was used to analyze operation time of the 2 groups and chi-square test was used to analyze the data of patients’ satisfaction and asymmetry occurrence. P<0.05 was considered as statistically significant. Results:The mean operation time was (85.1 ± 17.8) min during computer assisted surgery versus (62.2±11.7) min during conventional surgery. The difference between the two groups was statistically significant ( t=3.53, P=0.020). Neither group showed noticeable resected bone shifting or soft tissue drooping. One patient in the conventional surgery group had bone nonunion on the right zygoma and partial absorption of the left zygomatic bone. The incidence of asymmetry in the computer-assisted group was 3.8% (1/26, surgical correction was not required), and 33.3% in the conventional surgery group (3/9, one patient required surgical correction). There was a statistically significant difference between the two groups ( χ2=6.179, P=0.046). Patients’ satisfaction in the computer-assisted group was 100% (26/26), and 78% (7/9) in the conventional surgery group ( χ2=7.929, P=0.019). Comparisons between the postoperative CT and preoperative simulation CT images showed that the position deviation of the resected bones was (0.21 ± 0.19) mm. Conclusions:In the present study, improved precision of zygomatic bone resection and bone setback was achieved in reduction malarplasty by using the angled double L-shaped osteotomies with computer assistance. Moreover, complication occurrences (asymmetry, bone nonunion etc.) were significantly decreased. Also, patients’ expectation was better achieved with this method.

Traumatic brain injury (TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes, but the pathogenesis remains poorly understood. In this study, we aimed to investigate the causal role of acrolein, a typical lipid peroxidation product, in TBI-induced coagulopathy, and further explore the underlying molecular mechanisms. We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy. Using a controlled cortical impact mouse model, we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor (VWF). Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that acrolein over-activated autophagy, and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway. In addition, we demonstrated that acrolein was produced in the perilesional cortex, affected endothelial cell integrity, and disrupted the blood-brain barrier. In conclusion, in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage, providing an alternative therapeutic target.

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.

Traumatic brain injury (TBI) triggers the activation of the endogenous coagulation mechanism, and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors, also known as protease-activated receptors (PARs). However, thrombin is one of the most critical factors in secondary brain injury. Thus, the PARs may be effective targets against hemorrhagic brain injury. Since the PAR1 antagonist has an increased bleeding risk in clinical practice, PAR4 blockade has been suggested as a more promising treatment. Here, we explored the expression pattern of PAR4 in the brain of mice after TBI, and explored the effect and possible mechanism of BMS-986120 (BMS), a novel selective and reversible PAR4 antagonist on secondary brain injury. Treatment with BMS protected against TBI in mice. mRNA-seq analysis, Western blot, and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes, and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process. Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI, and suggest that BMS has a potential clinical application in the management of TBI.