TREATMENT OF THORACOLUMBAR FRACTURES BY CLOSED REDUCTION VIA A PERCUTANEOUS SOLID PEDICLE SCREW

ABSTRACT Objectives: Investigate the effect of closed reduction and per- cutaneous pedicle screw fixation in treating thoracolumbar fractures. Methods: This retrospective study analyzed 12 cases of single-segment thoracolumbar spine fractures without spinal cord and nerve injury at our department from March 2016 to September 2017. Patients were treated with closed reduction, percutaneous reduction, and internal fixation with solid pedicle screws. The operation time, intraoperative blood loss, anterior vertebral body height ratio (AVHR), Cobb angle (CA) of sagittal kyphosis, and VAS of back pain were determined and statistically compared. Results: The average operation time was 147.2 ± 45.6 min, and the average intraoperative bleeding was 67.8 ± 34.2 mL. All fractured vertebrae were completely reduced, their height was restored, and kyphosis was corrected. The average follow-up period was 10.6 ± 2.7 months, with significant improvements seen in the AVHR, CA of sagittal kyphosis, and VAS score (P < 0.01). One case had a broken rod after three months, and another had a postoperative infection. All the patients achieved bony healing. Conclusion: The treatment of thoracolumbar fractures by closed reduction and internal fixation with a percutaneous solid pedicle screw is simple, effective, and economical. Level of Evidence VI; Therapeutic Study, Case Series

Tumor Endothelium Marker-8 Based Decoys Exhibit Superiority over Capillary Morphogenesis Protein-2 Based Decoys as Anthrax Toxin Inhibitors

Anthrax toxin is the major virulence factor produced by Bacillus anthracis. The toxin consists of three protein subunits: protective antigen (PA), lethal factor, and edema factor. Inhibition of PA binding to its receptors, tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2) can effectively block anthrax intoxication, which is particularly valuable when the toxin has already been overproduced at the late stage of anthrax infection, thus rendering antibiotics ineffectual. Receptor-like agonists, such as the mammalian cell-expressed von Willebrand factor type A (vWA) domain of CMG2 (sCMG2), have demonstrated potency against the anthrax toxin. However, the soluble vWA domain of TEM8 (sTEM8) was ruled out as an anthrax toxin inhibitor candidate due to its inferior affinity to PA. In the present study, we report that L56A, a PA-binding-affinity-elevated mutant of sTEM8, could inhibit anthrax intoxication as effectively as sCMG2 in Fisher 344 rats. Additionally, pharmacokinetics showed that L56A and sTEM8 exhibit advantages over sCMG2 with better lung-targeting and longer plasma retention time, which may contribute to their enhanced protective ability in vivo. Our results suggest that receptor decoys based on TEM8 are promising anthrax toxin inhibitors and, together with the pharmacokinetic studies in this report, may contribute to the development of novel anthrax drugs

The improved efficacy of Sifuvirtide compared with enfuvirtide might be related to its selectivity for the rigid biomembrane, as determined through surface plasmon resonance

<div><p>Most mechanistic studies on human immunodeficiency virus (HIV) peptide fusion inhibitors have focused on the interactions between fusion inhibitors and viral envelope proteins. However, the interactions of fusion inhibitors with viral membranes are also essential for the efficacy of these drugs. Here, we utilized surface plasmon resonance (SPR) technology to study the interactions between the HIV fusion inhibitor peptides sifuvirtide and enfuvirtide and biomembrane models. Sifuvirtide presented selectivity toward biomembrane models composed of saturated dipalmitoylphosphatidylcholine (DPPC) (32-fold higher compared with unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [POPC]) and sphingomyelin (SM) (31-fold higher compared with POPC), which are rigid compositions enriched in the HIV viral membrane. In contrast, enfuvirtide showed no significant selectively toward these rigid membrane models. Furthermore, the bindings of sifuvirtide and enfuvirtide to SM bilayers were markedly higher than those to monolayers (14-fold and 23-fold, respectively), indicating that the inner leaflet influences the binding of these drugs to SM bilayers. No obvious differences were noted in the bindings of either peptide to the other mono- and bilayer models tested, illustrating that both peptides interact with these membranes through surface-binding. The bindings of the inhibitor peptides to biomembranes were found to be driven predominantly by hydrophobic interactions rather than electrostatic interactions, as determined by comparing their affinities to those of positively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine (EPC) to zwitterionic membrane models. The improved efficiency of sifuvirtide relative to enfuvirtide might be related to its ability to adsorb on rigid lipidic areas, such as the viral envelope and lipid rafts, which results in an increased sifuvirtide concentration at the fusion site.</p></div

Equilibrium Dissociation Constants Determined by SPR for the Interaction of Sifuvirtide with Lipid Monolayers (HPA Chip) and Bilayers (L1 Chip)^*.

<p>Equilibrium Dissociation Constants Determined by SPR for the Interaction of Sifuvirtide with Lipid Monolayers (HPA Chip) and Bilayers (L1 Chip)^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0171567#t002fn001" target="_blank">*</a>}.</p

Bindings of Enfuvirtide to SM Monolayers (HPA Chip) and Bilayers (L1 Chip).

<p>Panels A and B: Sensorgrams of the binding of enfuvirtide to an SM monolayer (panel A) and bilayer (panel B). Panels C and D: Corresponding relationships between the equilibrium binding response (RUeq) and the peptide concentration (C). The data were fit using the steady-state affinity model. The enfuvirtide concentrations used were 1.95, 3.91, 7.81, 15.63, 31.25, and 62.5 μM. The additional lines parallel to the y-axis indicate the K_D value.</p

Equilibrium Dissociation Constants Determined by SPR for the Interaction of Enfuvirtide from Monolayers (HPA Chip) and Bilayers (L1 Chip)^*.

<p>Equilibrium Dissociation Constants Determined by SPR for the Interaction of Enfuvirtide from Monolayers (HPA Chip) and Bilayers (L1 Chip)^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0171567#t004fn001" target="_blank">*</a>}.</p

Multi-Omics Identified THDCA as a Key Contributor to Hyperlipidemia and as a Potential Therapeutic Agent

Background: In recent years, with the change in human dietary habits, hyperlipidemia (HLP) has become a common chronic disease. Hyperlipidemia is closely related to the incidence of cardiovascular diseases. Due to the increasing incidence and mortality from cardiovascular diseases, it is imperative to develop new medications for reducing lipid levels. With the aim of discovering new treatment options for hyperlipidemia, we conducted a multi-omics analysis of a potential endogenous bile acid compound. Methods: Two hyperlipidemia models were established by feeding rats and mice with a high-fat diet. Serum and fecal specimens of rats with hyperlipidemia were collected. Through the combined analysis of lipid metabolism sequencing, 16S RNA intestinal flora sequencing, and bile acid targeted metabolism sequencing, taurohyodeoxycholic acid (THDCA) was found to be a potential lipid-lowering compound. A mouse hyperlipidemia model was developed to verify the anti-hyperlipidemia function of THDCA. Results: Analysis of serum lipid metabolites revealed that the synthesis of bile acid was one of the metabolic pathways that showed significant alterations. 16S RNA sequencing of intestinal flora also found that high-fat diet intake greatly influenced both primary and secondary bile acid biosynthesis. Analysis of bile acid metabolites in the serum and liver tissue found that THDCA in the secondary bile acids is a potential biomarker of hyperlipidemia. Verification experiments in mice confirmed the beneficial function of THDCA in lowering abnormal lipid levels induced by a high-fat diet. Conclusions: THDCA has been identified as a biomarker of hyperlipidemia and has shown potential for the treatment of hyperlipidemia