Comparison of Modified K-wire Fixation with Open Reduction and Internal Fixation (ORIF) for Unstable Colles Fracture in Elderly Patients.

OBJECTIVE: Open reduction and internal fixation (ORIF) is the standard treatment of unstable Colles fracture among the elderly. Modified percutaneous K-wire fixation is becoming increasingly popular in recent years. However, there is controversy concerning its appropriate use. This study aimed to compare the early safety and efficacy of the two different treatments and provide an alternative method for the treatment of unstable Colles fracture among the older population. METHODS: Electronic medical records of 60 consecutive unstable Colles fractures patients who underwent surgery from June 2019 to October 2021, by modified percutaneous K-wire fixation (30 patients) or ORIF (30 patients), were reviewed retrospectively. All cases were followed up for 3 months. The outcomes of patients were assessed with operation time, intraoperative blood loss, visual analog score (VAS) for wrist joint pain, palmar tilt (PT), radial inclination (RI), radial height (RH), Gartland-Werley score, total hospitalization costs, hospital stays, postoperative complications, and patient subjective satisfaction. General patient information was also collected. Independent Student's t-test or Mann-Whitney U test were used to compare continuous data. Pearson's chi-square test or Fisher's exact test were used to analyze the categorical data. RESULTS: The operation time and intraoperative blood loss were significantly shorter in the K-wire group than in the ORIF group (p < 0.05). Compared with the ORIF group, the VAS of the K-wire group was significantly lower at 1 and 3 days postoperatively (p < 0.05), and no significant differences were observed in VAS between the two groups preoperatively and 7 days postoperatively (p > 0.05). There were no significant differences in the PT, RI, and RH between the two groups preoperatively and at 1, 4, and 8 weeks postoperatively (p > 0.05). Patients in the K-wire group had significantly shorter hospital stays and lower total hospital costs (p < 0.05). All patients were followed up for 3 months, and there was no significant difference in the Gartland-Werley score between the two groups (p > 0.05). Compared with the ORIF group, postoperative complications were lower, and patient subjective satisfaction was higher in the K-wire group, but there were no significant differences (p > 0.05). CONCLUSIONS: Modified percutaneous K-wire fixation in the treatment of unstable Colles fracture among the elderly is a safe, effective, rapid, and minimally invasive surgical option for surgeons.

Two complete mitochondrial genomes in Scolopendra and a comparative analysis of tRNA rearrangements in centipedes.

BACKGROUND: Centipedes are one of the oldest terrestrial arthropods belonging to the sub phylum Myriapoda. With the expansion of our understanding of the application of the two centipedes Scolopendra morsitans and Scolopendra hainanum, belonging to the order Scolopendromorpha, an exhaustive classification was required. Although consensus has been reached on the phylogeny of Chilopoda based on morphological traits, recent analyses based on molecular data exhibited differences in results. METHODS AND RESULTS: The mitochondrial genome sequences of S. morsitans and S. hainanum were obtained by next-generation sequencing. S. morsitans contains 13 PCGs, two rRNAs, 11 tRNAs, and one CR. whereas S. hainanum contains 12 PCGs, of which ATP8 remains unpredicted, two rRNAs, 14 tRNAs, and one CR. An obvious tRNA rearrangement was found in the genus Scolopendra. S. morsitans exhibited a loss of trnW, trnC, trnI, trnK, trnD, trnA, trnN, trnQ, trnF, trnT, trnS, trnL, and trnV, and a repeat of trnR and trnL. S. hainanum exhibited a loss of trnQ, trnC, trnW, trnI, trnD, trnQ, trnP, and trnV. Phylogenetic analyses of centipedes based on 12 PCGs supported the sister relationship between the orders Geophilomorpha and Lithobiomorpha and a close relationship between Scolopendra dehaani and S. hainanum. CONCLUSIONS: The new mitogenomes determined in this study provide new genomic resources for gene rearrangements and contribute to the understanding of the evolution of gene rearrangement in Chilopoda.

Endothelial progenitor cells promote neural stem cell proliferation in hypoxic conditions through VEGF via the PI3K/AKT pathway.

Neurons and vascular cells compose neurovascular niches in the central nervous system where endothelial cells can promote neurogenesis via direct and indirect effects. Neurocytes and vascular cells are gravely destroyed upon spinal cord injury, which severely affects spinal motor functions. Neurogenesis originates from neural stem cells (NSCs) and endothelial cells derived from endothelial progenitor cells (EPCs) in the spinal cord. To demonstrate whether EPCs promote NSC proliferation, we cultured NSCs with EPC-conditioned medium from hypoxic conditions (CM) and EPC-unconditioned medium (UCM), i.e. endothelial cell basal medium-2, as a control. The number of S-phase cells in CM were 54.73 ± 0.67 whereas those in UCM were 26.30 ± 0.43, and the number of cells in CM was higher than that in UCM (0.32 ± 0.0019 vs. 0.55 ± 0.0029). We hypothesized that the cell proliferation was promoted by vascular endothelial growth factor A (VEGFA), which is secreted by EPCs in hypoxic conditions. We then used VEGF shRNA to decrease VEGFA secretion by EPCs. NSCs were cultured in conditioned medium from shRNA transfected EPCs under hypoxia (shRNA-CM) and EPC-conditioned medium under hypoxia (CM). The number of S-phase cells in the shRNA-CM was 36.86 ± 0.49 whereas that in CM was 53.61 ± 0.89, and the number of cells in the shRNA-CM was lower than that in CM (0.55 ± 0.0032 vs. 0.34 ± 0.0029). These data indicate that EPCs could promote NSC proliferation in hypoxic condition through VEGFA secretion.

Treadmill exercise ameliorates focal cerebral ischemia/reperfusion-induced neurological deficit by promoting dendritic modification and synaptic plasticity via upregulating caveolin-1/VEGF signaling pathways.

Dendritic and synaptic plasticity in the penumbra are important processes and are considered to be therapeutic targets of ischemic stroke. Treadmill exercise is known to be a beneficial treatment following stroke. However, its effects and potential mechanism in promoting dendritic and synaptic plasticity remain unknown. We have previously demonstrated that the caveolin-1/VEGF signaling pathway plays a positive role in angiogenesis and neurogenesis. Here, we further investigated the effects of treadmill exercise on promoting dendritic and synaptic plasticity in the penumbra and whether they involve the caveolin-1/VEGF signaling pathway. A middle cerebral artery occlusion (MCAO) animal model was established, and rats were randomly divided into eleven groups. At 2 days after MCAO, rats were subjected to treadmill exercise for 7 or 28 days. Daidzein (a specific inhibitor of caveolin-1, 0.4 mg/kg) was used to confirm the effect of caveolin-1/VEGF signaling on exercise-mediated dendritic and synaptic plasticity. Neurobehavioral performance, tissue morphology and infarct volumes were detected by Modified Neurology Severity Score (mNSS), Hematoxylin-eosin (HE), and Nissl staining, while neural plasticity and its molecular mechanism were examined by Golgi-Cox staining, transmission electron microscopy, western blot analysis and immunofluorescence. We found that treadmill exercise promoted dendritic plasticity in the penumbra, consistent with the significant increase in caveolin-1 and VEGF expression; improved neurological recovery; and reduced infarct volume. In contrast to the positive effects of the treadmill, a caveolin-1 inhibitor abrogated the dendritic and synaptic plasticity. Furthermore, we observed that treadmill exercise-induced improved dendritic and synaptic plasticity were significantly inhibited by the caveolin-1 inhibitor, consistent with the lower expression of caveolin-1 and VEGF, as well as the worse neurobehavioral state. The findings indicate that treadmill exercise ameliorates focal cerebral ischemia/reperfusion-induced neurological deficit by promoting dendritic and synaptic plasticity via upregulating caveolin-1/VEGF signaling pathways.

Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer's-Associated Aß Oligomers.

Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid ß oligomers (AßOs). AßOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AßO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AßOs to surface membranes. Here, we show that AßO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs). This method gives a soluble membrane protein library (SMPL)--a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AßOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AßO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AßO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AßO binding will provide a useful experimental antagonist for future mechanistic studies of AßOs in Alzheimer's model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AßO binding antagonists, and illustrate in general how a SMPL Nanodisc system can facilitate drug discovery for membrane protein targets.