FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury.

BACKGROUND: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. METHODS: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. RESULTS: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. CONCLUSIONS: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.

Successful replantation of amputated facial tissues by supermicrosurgery.

BACKGROUND: Although replantation of amputated facial segments remains challenging in reconstructive surgery, it offers excellent aesthetic and functional outcomes. METHODS: From May 2004 to October 2019, 12 patients underwent replantation of amputated facial tissues by supermicrosurgery. The case details, such as the rationale for replantation, the operation method, and postoperative therapy, are described. Four cases are discussed to demonstrate the replantation of different facial parts. RESULTS: Facial tissue replantation was successful in all 12 patients without secondary surgery. The cases included the nose (1 patient), ears (8 patients), lips (2 patients), and one of the soft tissue segments surrounding the lower jaw. Venous congestion occurred in three patients who received a solitary arterial repair and were treated with bloodletting. All patients expressed satisfaction with the cosmetic and functional results at the final follow-up. CONCLUSIONS: Supermicrosurgical facial tissue replantation is a promising and effective procedure for providing patients with the best aesthetic and functional outcomes.

[Clinical application of the free superficial peroneal artery perforator flap].

OBJECTIVE: To investigate the applied anatomy of the superficial peroneal artery perforator flap and report the clinical results of repairing the soft tissue defects with free perforator flaps. METHODS: 15 fresh cadavers were injected with a modified lead oxide-gelatin mixture for three-dimensional visualization reconstruction using a 16-slice spiral computed tomography scanner and specialized software (Materiaise's interactive medical image control system, MIMICS). The origin, course and distribution of the superficial peroneal artery perforator in the anterolateral leg region were observed. Clinically 6 cases with hand defects and 6 cases with feet defects were treated with free superficial peroneal artery perforator flap transplantation. The defect size ranged from 3.0 cm x 4.5 cm to 5.0 cm x 11.0 cm. RESULTS: The diameter of the superficial peroneal artery is (1.2 +/- 0.3) mm at its origin from the anterior tibial artery 5 cm below the fibula head. It is (5.6 +/- 1.8) cm in length. This artery is truly anastomosed with other perforators to form the chain of superficial peroneal nerve accessory artery. The superficial peroneal artery perforators [outer diameter (0.7 +/- 0.2) mm] with a vein are in the anterolateral leg region, supplying the skin in proximal-middle region. All the 12 cases were treated successfully. The clinical results were satisfactory after 3-12 months of following-up. CONCLUSIONS: The superficial peroneal artery perforator flap has constantly, reliable blood supply, and good texture. It is a good option for repairing soft-tissue defect with free transfer.