Melatonin supplementation protects against traumatic colon injury by regulating SERPINA3N protein expression.

Traumatic colon injury (TCI) is a typical injury with high mortality. Prolongation of the intervention time window is a potentially useful approach to improving the outcomes of TCI casualties. This study aimed to identify the pathological mechanisms of TCI and to develop effective strategies to extend the survival time. A semicircular incision was made to prepare a TCI model using C57BL/6 mice. An overview of microbiota dysregulation was achieved by metagenome sequencing. Protein expression reprogramming in the intestinal epithelium was investigated using proteomics profiling. The mice that were subjected to TCI died within a short period of time when not treated. Gut symbiosis showed abrupt turbulence, and specific pathogenic bacteria rapidly proliferated. The protein expression in the intestinal epithelium was also reprogrammed. Among the differentially expressed proteins, SERPINA3N was overexpressed after TCI modeling. Deletion of Serpina3n prolonged the posttraumatic survival time of mice with TCI by improving gut homeostasis in vivo. To promote the translational application of this research, the effects of melatonin (MLT), an oral inhibitor of the SERPINA3N protein, were further investigated. MLT effectively downregulated SERPINA3N expression and mitigated TCI-induced death by suppressing the NF-κB signaling pathway. Our findings prove that preventive administration of MLT serves as an effective regimen to prolong the posttraumatic survival time by restoring gut homeostasis perturbed by TCI. It may become a novel strategy for improving the prognosis of patients suffering from TCI.

Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury.

BACKGROUND: Traumatic colon injury (TCI) is a common disease during wartime. Prolongation of posttraumatic survival time is an effective approach to patient outcome improvement. However, there is a lack of basic research in this field. This study aimed to elucidate the mechanisms underlying TCI progression and to develop novel regimens to buy time for TCI patients on the battlefield. METHODS: A total of 669 Sprague-Dawley rats were used in this study. Surgical colon incision was performed to generate the TCI rat model. The landscape of colon microbiota compositions was depicted using 16S rRNA sequencing and metabolites in the intestinal contents were detected by metabolomics profiling. The signaling transduction in the intestinal epithelium was investigated using antibody microarrays and Western blotting. The enzyme-linked immunosorbent assay was conducted to measure the levels of interleukin-6 and tumor necrosis factor-α in intestines and plasma for the detection of inflammatory responses. Diamine oxidase, D-lactate and endotoxin in plasma and protein expression of zonula occludens 1 and occludin were selected as the indicators of intestinal barrier permeability. To investigate alterations of microbiota symbiosis, the relative abundances of specific bacterial genera were detected using quantitative real-time PCR. RESULTS: As a type of lethal injury, TCI induced acute disruption of intestinal homeostasis, characterized by inflammatory responses, intestinal barrier hyperpermeability and microbiota dysbiosis (P < 0.05). Significant alterations in bacterial metabolic patterns were detected with decreases in many metabolites. After a series of screenings, we found that oral administration of asparagine (Asn) and 3-indolepropionic acid (IPA) effectively prolonged posttraumatic survival time [Asn plus IPA vs. Vehicle: hazard ratio (HR) = 0.105, 95% CI 0.031-0.356, P = 0.0003] and restored intestinal homeostasis in TCI rats (P < 0.05). Mechanistically, this combinational strategy protected the rats against TCI through synergistic activation of Akt signaling in the intestinal epithelium (P < 0.05). CONCLUSIONS: Abrupt dysregulation of intestinal homeostasis plays a critical role in the progression toward TCI-induced death. Oral administration of Asn plus IPA may serve as an effective regimen to restore intestinal functions and prolong the posttraumatic survival time.

A novel computer-assisted drill guide template for thoracic pedicle screw placement: a cadaveric study.

INTRODUCTION: The objective of this study was to develop a novel, patient-specific, navigational template for thoracic pedicle screw placement. METHODS: Twenty thoracic cadaver specimens were randomly divided into two groups of 10: the navigational template group and the free-hand group. A volumetric CT scan was performed on each thoracic vertebra, and a three-dimensional reconstruction model was generated. A drill template was designed with a surface that was the inverse of the posterior vertebral surface. Each drill template and its corresponding vertebra were manufactured using a rapid prototyping technique and tested for violation. Two hundred and forty screws were implanted into the thoracic spines and the positions of the screws were evaluated. RESULTS: Two hundred and forty thoracic screws were inserted using either the navigational template method or the free-hand method. The accuracy rate and incidence of risk for setting thoracic pedicle screws differed statistically between the two methods (P < 0.05): The navigational template method had a higher accuracy rate and a lower incidence of risk than the free-hand method. Moreover, the free-hand method had a significant learning curve, whereas a learning curve for the navigational template method was not obvious. CONCLUSION: We have developed a novel, patient-specific, navigational template for thoracic pedicle screw placement with good applicability and high accuracy.