Clinical epidemiology and a novel predicting nomogram of central line associated bloodstream infection in burn patients.

Burn patients are at high risk of central line-associated bloodstream infection (CLABSI). However, the diagnosis of such infections is complex, resource-intensive, and often delayed. This study aimed to investigate the epidemiology of CLABSI and develop a prediction model for the infection in burn patients. The study analysed the infection profiles, clinical epidemiology, and central venous catheter (CVC) management of patients in a large burn centre in China from January 2018 to December 2021. In total, 222 burn patients with a cumulative 630 CVCs and 5,431 line-days were included. The CLABSI rate was 23.02 CVCs per 1000 line-days. The three most common bacterial species were Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa; 76.09% of isolates were multidrug resistant. Compared with a non-CLABSI cohort, CLABSI patients were significantly older, with more severe burns, more CVC insertion times, and longer total line-days, as well as higher mortality. Regression analysis found longer line-days, more catheterisation times, and higher burn wounds index to be independent risk factors for CLABSI. A novel nomogram based on three risk factors was constructed with an area under the receiver operating characteristic curve (AUROC) value of 0.84 (95% CI: 0.782-0.898) with a mean absolute error of calibration curve of 0.023. The nomogram showed excellent predictive ability and clinical applicability, and provided a simple, practical, and quantitative strategy to predict CLABSI in burn patients.

Characterization and biocontrol mechanism of Streptomyces olivoreticuli as a potential biocontrol agent against Rhizoctonia solani.

Rhizoctonia solani is a widespread and devastating plant pathogenic fungus that infects many important crops. This pathogen causes tobacco target spot, a disease that is widespread in many tobacco-growing countries and is destructive to tobacco. To identify antagonistic microorganisms with biocontrol potential against this disease, we isolated Streptomyces strains from forest inter-root soil and screened a promising biocontrol strain, ZZ-21. Based on in vitro antagonism assays, ZZ-21 showed a significant inhibitory effect on R. solani and various other phytopathogens. ZZ-21 was identified as Streptomyces olivoreticuli by its phenotypic, genetic, physiological and biochemical properties. Complete genome sequencing revealed that ZZ-21 harbored numerous antimicrobial biosynthesis gene clusters. ZZ-21 significantly reduced the lesion length in detached inoculated leaf assays and reduced the disease index under greenhouse and field conditions. Based on an in vitro antagonistic assay of ZZ-21 culture, the strain exhibited an antifungal activity against R. solani in a dose-dependent manner. The culture filtrate could impair membrane integrity, possibly through membrane lipid peroxidation. ZZ-21 could secrete multiple extracellular enzymes and siderophores. According to a series of antifungal assays, the extracellular metabolites of ZZ-21 contained antimicrobial bioactive compounds composed of proteins/peptides extracted using ammonium sulfate precipitation, which were stable under stress caused by high temperature and protease K. The EC50 value for ammonium sulfate precipitation was determined to be 21.11 µg/mL in this study. Moreover, the proteins/peptides also exhibited biocontrol ability and were observed to alter the plasma membrane integrity of R. solani which were evaluated by biocontrol efficacy assays on detached tobacco leaves and PI staining. Overall, strain ZZ-21 shows the potential to be developed into a biopesticide against tobacco target spot disease.

Anti-Aging Constituents from Pinus morrisonicola Leaves.

Pinus morrisonicola Hayata is a unique plant species found in Taiwan. Previous studies have identified its anti-hypertensive, anti-oxidative, and anti-inflammatory effects. In this study, a bioactivity-guided approach was employed to extract 20 compounds from the ethyl acetate fraction of the ethanol extract of Pinus morrisonicola Hayata's pine needles. The anti-aging effects of these compounds were investigated using HT-1080 cells. The structures of the purified compounds were confirmed through NMR and LC-MS analysis, revealing the presence of nine flavonoids, two lignans, one coumarin, one benzofuran, one phenylic acid, and six diterpenoids. Among them, PML18, PML19, and PML20 were identified as novel diterpene. Compounds 3, 4, and 5 exhibited remarkable inhibitory effects against MMP-2 and showed no significant cell toxicity at 25 µM. Although the purified compounds showed lower activity against Pro MMP-2 and Pro MMP-9 compared to the ethyl acetate fraction, we speculate that this is the result of synergistic effects.

Characterization of a novel victorivirus from Nigrospora chinensis, a fungus isolated from tobacco.

Here, we characterized a new mycovirus from the fungus Nigrospora chinensis, which was named "Nigrospora chinensis victorivirus 1" (NcVV1). The NcVV1 genome is 5283 bp in length, containing two continuous open reading frames (ORFs), ORF1 and ORF2. ORF1 and ORF2 were predicted to encode a putative coat protein (CP) and an RNA-dependent RNA polymerase (RdRp), respectively. The stop codon of ORF1 overlaps with the start codon of ORF2 by the tetranucleotide sequence AUGA. Phylogenetic analysis based on amino acid sequences of RdRp and CP indicated that NcVV1 clustered with members of the genus Victorivirus in the family Totiviridae. To our knowledge, this was the first report of a mycovirus infecting N. chinensis.

Development of gestational diabetes mellitus in women with periodontitis in early pregnancy: A population-based clinical study.

AIM: This study aimed to determine whether periodontitis in early pregnancy and periodontal therapy during gestation affect the incidence of gestational diabetes mellitus (GDM) through a population-based clinical study. MATERIALS AND METHODS: Subjects without periodontitis at 1-4 weeks of gestation who met our inclusion criteria were enrolled in the non-periodontitis group. Periodontitis patients who agreed or refused to receive periodontal therapy during pregnancy were separately enrolled in the periodontitis treated or untreated group. At 12-16 weeks of gestation, gingival crevicular fluid (GCF) and venous blood were collected for analyses of bacterial species and serum inflammatory mediators, respectively. At 24-28 weeks of gestation, GDM patients were identified by oral glucose tolerance tests. The association tests were performed using Chi-squared statistics and regression analyses. RESULTS: The complete data of 3523 pregnant women were recorded during the study period. GDM incidence among the untreated periodontitis participants (84/749, 11.21%) was significantly higher than that among the non-periodontitis participants (108/2255, 4.79%) (p < .05), and periodontal treatment during gestation reduced the incidence from 11.21% (untreated group) to 7.32% (38/519, treated group) (p < .05). Based on multiple logistic regression analyses, it was found that periodontitis in early pregnancy was associated with GDM, and three-step regression analyses showed that Porphyromonas gingivalis (P. gingivalis) and the serum TNF-α and IL-8 levels played a role in the association between untreated periodontitis and GDM. Furthermore, Pearson's correlation test indicated that the existence of P. gingivalis in GCF was positively correlated with high serum levels of these two inflammatory mediators. CONCLUSIONS: This study establishes a connection between periodontitis in early pregnancy and GDM and demonstrates that the presence of P. gingivalis is associated with high levels of inflammatory mediators in serum, and thereby may contribute to the development of GDM. In-depth mechanistic studies are needed to further support these findings.

New Trichothecenes Isolated from the Marine Algicolous Fungus Trichoderma brevicompactum.

Eight trichothecenes, including four new compounds 1-4 and four known entities 5-8, together with one known cyclonerane (9) were isolated from the solid-state fermentation of Trichoderma brevicompactum NTU439 isolated from the marine alga Mastophora rosea. The structures of 1-9 were determined by 1D/2D NMR (nuclear magnetic resonance), MS (mass spectrometry), and IR (infrared spectroscopy) spectroscopic data. All of the compounds were evaluated for cytotoxic activity against HCT-116, PC-3, and SK-Hep-1 cancer cells by the SRB assay, and compound 8 showed promising cytotoxic activity against all three cancer cell lines with the IC50 values of 3.3 ± 0.3, 5.3 ± 0.3, and 1.8 ± 0.8 µM, respectively. Compounds 1-2, 4-6, and 7-8 potently inhibited LPS-induced NO production, and compounds 5 and 8 showed markedly inhibited gelatinolysis of MMP-9 in S1 protein-stimulated THP-1 monocytes.

Cytotoxicity Effect of Constituents of Pinus taiwanensis Hayata Twigs on B16-F10 Melanoma Cells.

Pinus taiwanensis Hayata (Pinaceae) is an endemic plant in Taiwan. According to the Chinese Materia Medica Grand Dictionary, the Pinus species is mainly used to relieve pain, and eliminate pus and toxicity. In this study, nineteen compounds were isolated from the ethyl acetate layer of the ethanolic extract of P. taiwanensis Hayata twigs using bioassay-guided fractionation, and their anti-melanoma effects were investigated through a B16-F10 mouse melanoma cell model. The structures of the purified compounds were identified by 2D-NMR, MS, and IR, including 1 triterpenoid, 9 diterpenoids, 2 lignans, 4 phenolics, 1 phenylpropanoid, 1 flavonoid, and 1 steroid. Among them, compound 3 was found to be a new diterpene. Some of the compounds (2, 5, 6, 17, 18) showed moderate cytotoxicity effects. On the other hand, the anti-melanoma effect was no better than that from the original ethyl acetate layer. We presumed it resulted from the synergistic effect, although further experimentation needs to be performed.

An improved production and purification protocol for recombinant soluble human fibroblast activation protein alpha.

Fibroblast activation protein alpha (FAP) is a cell-surface expressed type II glycoprotein that has a unique proteolytic activity. FAP has active soluble forms that retain the extracellular portion but lack the transmembrane domain and cytoplasmic tail. FAP expression is normally very low in adult tissue but is highly expressed by activated fibroblasts in sites of tissue remodelling. Thus, FAP is a potential biomarker and pharmacological target in liver fibrosis, atherosclerosis, cardiac fibrosis, arthritis and cancer. Understanding the biological significance of FAP by investigating protein structure, interactions and activities requires reliable methods for the production and purification of abundant pure and stable protein. We describe an improved production and purification protocol for His6-tagged recombinant soluble human FAP. A modified baculovirus expression construct was generated using the pFastBac1 vector and the gp67 secretion signal to produce abundant active soluble recombinant human FAP (residues 27-760) in insect cells. The FAP purification protocol employed ammonium sulphate precipitation, ion exchange chromatography, immobilised metal affinity chromatography and ultrafiltration. High purity was achieved, as judged by gel electrophoresis and specific activity. The purified 82 kDa FAP protein was specifically inhibited by a FAP selective inhibitor, ARI-3099, and was inhibited by zinc with an IC50 of 25 µM. Our approach could be adopted for producing the soluble portions of other type II transmembrane glycoproteins to study their structure and function.

The radiographic, pulmonary, and clinical outcomes of patients with severe rigid spinal deformities treated via halo-pelvic traction.

BACKGROUND: The severe rigid deformity patients with pulmonary dysfunction could not tolerate complicated corrective surgery. Preoperative traction are used to reduce the curve magnitude and improve the pulmonary function before surgery, including halo-gravity traction (HGT) and halo-pelvic traction (HPT). The present study aimed to retrospectively compare the radiographic, pulmonary and clinical outcomes of preoperative HGT and HPT in severe rigid spinal deformity with respiratory dysfunction. METHODS: 81 cases of severe rigid kyphoscoliosis treated with preoperative traction prior to corrective surgery for spinal deformity between 2016 and 2019 were retrospectively reviewed. Two patient groups were compared, HPT group (N = 30) and HGT group (N = 51). Patient demographics, coronal and sagittal Cobb angles and correction rates, pulmonary function, traction time, osteotomy grade, and postoperative neurological complications were recorded for all cases. RESULTS: The coronal Cobb angle was corrected from 140.67 ± 2.63 to a mean of 120.17 ± 2.93° in the HGT group, and from 132.32 ± 4.96 to 87.59 ± 3.01° in the HPT group (mean corrections 15.33 ± 1.53 vs. 34.86 ± 3.11 %) (P = 0.001). The mean major sagittal curve decreased from 134.28 ± 3.77 to 113.03 ± 4.57° in the HGT group and from 129.60 ± 8.45 to 65.61 ± 7.86° in the HPT group (P < 0.001); the mean percentage corrections were 16.50 ± 2.13 and 44.09 ± 9.78 % (P < 0.001). A significant difference in the pulmonary function test results was apparent between the two groups; the mean improvements in the FVC% of the HGT and HPT groups were 6.76 ± 1.85 and 15.6 ± 3.47 % (P = 0.024). The HPT group tended to exhibit more FEV% improvement than the HGT group, but the difference was not significant (5.15 ± 2.27 vs. 11.76 ± 2.22 %, P = 0.91). CONCLUSIONS: Patients with severe rigid kyphoscoliosis who underwent preoperative HPT exhibited better radiographic correction of the deformity, and pulmonary function, and required fewer osteotomies compared to the HGT group. Thus, HPT may be useful for severe rigid spinal deformity patients with pulmonary dysfunction.

Constituents of Aquilaria sinensis Leaves Upregulate the Expression of Matrix Metalloproteases 2 and 9.

In this novel study, we isolated 28 compounds from the leaves of Aquilaria sinensis (Lour.) Gilg based on a bioassay-guided procedure and also discovered the possible matrix metalloprotease 2 (MMP-2) and 9 (MMP-9) modulatory effect of pheophorbide A (PA). To evaluate the regulatory activity on MMP-2 and MMP-9, the HT-1080 human fibrosarcoma cells were treated with various concentrations of extracted materials and isolated compounds. PA was extracted by methanol from the leaves of A. sinensis and separated from the fraction of the partitioned ethyl acetate layer. PA is believed to be an active component for MMP expression since it exhibited significant stimulation on MMP-2 and proMMP-9 activity. When treating with 50 µM of PA, the expression of MMP-2 and MMP-9 were increased 1.9-fold and 2.3-fold, respectively. PA also exhibited no cytotoxicity against HT-1080 cells when the cell viability was monitored. Furthermore, no significant MMP activity was observed when five PA analogues were evaluated. This study is the first to demonstrate that C-17 of PA is the deciding factor in determining the bioactivity of the compound. The MMP-2 and proMMP-9 modulatory activity of PA indicate its potential applications for reducing scar formation and comparative medical purposes.

Risk factors for neurological complications in severe and rigid spinal deformity correction of 177 cases.

BACKGROUND: Difficult procedures of severe rigid spinal deformity increase the risk of intraoperative neurological injury. Here, we aimed to investigate the preoperative and intraoperative risk factors for postoperative neurological complications when treating severe rigid spinal deformity. METHODS: One hundred seventy-seven consecutive patients who underwent severe rigid spinal deformity correction were assigned into 2 groups: the neurological complication (NC, 22 cases) group or non-NC group (155 cases). The baseline demographics, preoperative spinal cord functional classification, radiographic parameters (curve type, curve magnitude, and coronal/sagittal/total deformity angular ratio [C/S/T-DAR]), and surgical variables (correction rate, osteotomy type, location, shortening distance of the osteotomy gap, and anterior column support) were analyzed to determine the risk factors for postoperative neurological complications. RESULTS: Fifty-eight patients (32.8%) had intraoperative evoked potentials (EP) events. Twenty-two cases (12.4%) developed postoperative neurological complications. Age and etiology were closely related to postoperative neurological complications. The spinal cord functional classification analysis showed a lower proportion of type A, and a higher proportion of type C in the NC group. The NC group had a larger preoperative scoliosis angle, kyphosis angle, S-DAR, T-DAR, and kyphosis correction rate than the non-NC group. The results showed that the NC group tended to undergo high-grade osteotomy. No significant differences were observed in shortening distance or anterior column support of the osteotomy area between the two groups. CONCLUSIONS: Postoperative neurological complications were closely related to preoperative age, etiology, severity of deformity, angulation rate, spinal cord function classification, intraoperative osteotomy site, osteotomy type, and kyphosis correction rate. Identification of these risk factors and relative development of surgical techniques will help to minimize neural injuries and manage postoperative neurological complications.

Stromal-derived Factor-1α signaling is involved in bone morphogenetic protein-2-induced odontogenic differentiation of stem cells from apical papilla via the Smad and Erk signaling pathways.

Stromal-derived factor-1α (SDF-1α) is a chemokine signaling molecule that binds to the transmembrane receptor CXC chemokine receptor-4 (CXCR4) and carries out important functions in development tissue homeostasis. SDF-1α signaling via CXCR4 regulates the recruitment of stem and precursor cells to support tissue-specific repair or regeneration. In this study, we examined the contribution of SDF-1α signaling to the odontogenic differentiation of stem cells from the apical papilla (SCAP) induced by bone morphogenic protein 2 (BMP-2). CXCR4 expression was detected in cultured SCAP and SDF-1α promoted the migration of SCAP in Transwell assays. Blocking SDF-1α signaling by treatment with siRNA significantly affected BMP-2-induced mineralized nodule formation and alkaline phosphatase (ALP) activity. Moreover, blocking SDF-1α signaling inhibited the BMP-2-induced early expression of runt-related factor-2 (Runx-2) and strongly suppressed the induction of dentin matrix protein 1 (DMP-1) and dentin sialophosphoprotein (DSPP) expression by BMP-2. Furthermore, the interaction between SDF-1α and BMP-2 signaling was mediated via intracellular Smads and Erk activation. In conclusion, our results demonstrated that SDF-1α can significantly promote the migration of SCAP. Moreover, we revealed corequirement of the SDF-1α/CXCR4 signaling pathways in the BMP-2-induced odontogenic differentiation of SCAP, and these findings may be applied in new strategies for dental pulp regeneration.

A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2.

Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. In addition, DPP4 binds to the spike protein of the MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulphate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion-exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor-binding domain (RBD) were measured using surface plasmon resonance and ELISA. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected by surface plasmon resonance or ELISA. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS, SARS-CoV-2 does not bind human DPP4.

Study on the correlation parameters of Class II malocclusion in child tooth dentition early stage by using 3D technique.

OBJECTIVE: To record the dentition, jaw and facial growth and development of children with class II malocclusion at the age of 7-8 years old in the early dental transitional stage with 3D technology and to provide the study basis for the growth and development parameters of normal children and children with class II malocclusion. METHODS: Twenty-four children who were suffering class-II malocclusion in the early dental transitional stage and received treatment between July 2016 and July 2017 in our hospital were selected as the study group, and 20 healthy children were selected as the control group in the same period. SIRONA CEREC dentition scanning, 3D reconstruction of the lower mandible and 3d MD face scanning were performed on the children. Relevant data were recorded and compared. RESULTS: The dentition scanning results suggested that the study group had significantly larger anterior overbite and anterior overjet and smaller width of the upper arch than the control group; there was a significant difference between the two groups (P<0.05). The 3D reconstruction of the lower mandible suggested that the study group had smaller Go angle and SNB angle and shorter ANS-Me distance, Go-Me distance and N-Me distance compared to the control group; the differences had statistical significance (P<0.05). The face scanning results demonstrated that the nasolabial angle and facial convexity angle of the study group were significantly larger than those in the control group, and the difference was statistically significant (P<0.05). CONCLUSION: The dentition scanning results suggested that the study group had significantly larger anterior overbite and anterior overjet and smaller width of the upper arch than the control group; there was a significant difference between the two groups (P<0.05). The 3D reconstruction of the lower mandible suggested that the study group had smaller Go angle and SNB angle and shorter ANS-Me distance, Go-Me distance and N-Me distance compared to the control group; the differences had statistical significance (P<0.05). The face scanning results demonstrated that the nasolabial angle and facial convexity angle of the study group were significantly larger than those in the control group, and the difference was statistically significant (P<0.05).

HDAC7 Ubiquitination by the E3 Ligase CBX4 Is Involved in Contextual Fear Conditioning Memory Formation.

Histone acetylation, an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that they may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4-24 h), which was involved in long-term CFC memory formation. We also showed that HDAC7 decreased via ubiquitin-dependent degradation. CBX4 was one of the HDAC7 E3 ligases involved in this process. Nur77, as one of the target genes of HDAC7, increased 6-24 h after CFC training and, accordingly, modulated the formation of CFC memory. Finally, HDAC7 was involved in the formation of other hippocampal-dependent memories, including the Morris water maze and object location test. The current findings facilitate an understanding of the molecular and cellular mechanisms of HDAC7 in the regulation of hippocampal-dependent memory.SIGNIFICANCE STATEMENT The current findings demonstrated the effects of histone deacetylase 7 (HDAC7) on hippocampal-dependent memories. Moreover, we determined the mechanism of decreased HDAC7 in contextual fear conditioning (CFC) through ubiquitin-dependent protein degradation. We also verified that CBX4 was one of the HDAC7 E3 ligases. Finally, we demonstrated that Nur77, as one of the important targets for HDAC7, was involved in CFC memory formation. All of these proteins, including HDAC7, CBX4, and Nur77, could be potential therapeutic targets for preventing memory deficits in aging and neurological diseases.

Myosin Va mediates BDNF-induced postendocytic recycling of full-length TrkB and its translocation into dendritic spines.

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival, neurite outgrowth and synaptic plasticity by activating the receptor tropomyosin receptor kinase B (TrkB, also known as NTRK2). TrkB has been shown to undergo recycling after BDNF stimulation. We have previously reported that full-length TrkB (TrkB-FL) are recycled through a Rab11-dependent pathway upon BDNF stimuli, which is important for the translocation of TrkB-FL into dendritic spines and for the maintenance of prolonged BDNF downstream signaling during long-term potentiation (LTP). However, the identity of the motor protein that mediates the local transfer of recycled TrkB-FL back to the plasma membrane remains unclear. Here, we report that the F-actin-based motor protein myosin Va (Myo5a) mediates the postendocytic recycling of TrkB-FL. Blocking the interaction between Rab11 and Myo5a by use of a TAT-tagged peptide consisting of amino acids 55-66 of the Myo5a ExonE domain weakened the association between TrkB-FL and Myo5a and thus impaired TrkB-FL recycling and BDNF-induced TrkB-FL translocation into dendritic spines. Finally, inhibiting Myo5a-mediated TrkB-FL recycling led to a significant reduction in prolonged BDNF downstream signaling. Taken together, these results show that Myo5a mediates BDNF-dependent TrkB-FL recycling and contributes to BDNF-induced TrkB spine translocation and prolonged downstream signaling.

Efficacy of tranexamic acid in reducing allogeneic blood products in adolescent idiopathic scoliosis surgery.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) surgery usually require prolonged operative times with extensive soft tissue dissection and significant perioperative blood loss, and allogeneic blood products are frequently needed. Methods to reduce the requirement for transfusion would have a beneficial effect on these patients. Although many previous studies have revealed the efficacy of tranexamic acid (TXA) in spinal surgery, there is still a lack of agreement concerning the reduction of both blood loss and transfusion requirements of large dose tranexamic acid (TXA) in surgery for adolescent idiopathic scoliosis (AIS). The objective of this study was to elevate the efficacy and safety of a large dose tranexamic acid (TXA) in reducing transfusion requirements of allogeneic blood products in adolescent idiopathic scoliosis (AIS) surgery using a retrospective study designed with historical control group. METHODS: One hundred thirty seven consecutive AIS patients who underwent surgery treatment with posterior spinal pedicle systems from August 2011 to March 2015 in our scoliosis center were retrospectively reviewed. Patients were divided into two groups, the TXA group and the historical recruited no TXA group (NTXA). Preoperative demographics, radiographic parameters, operative parameters, estimated blood loss (EBL), total irrigation fluid, number of patients requiring blood transfusion, mean drop of Hb (Pre-op Hb-Post-op Hb), haematocrit pre and post-surgery, mean volume of blood transfusion, hospitalization time, and adverse effect were recorded and compared. RESULTS: All the patients were successfully treated with satisfied clinical and radiographic outcomes. There were 71 patients in the TXA group and 66 patients in the NTXA group. The preoperative demographics were homogeneity between two groups (P > 0.05). There were no significant difference in average operative time between two groups (209 min vs 215 min, p >0.05). Number of patients in the TXA group showed a significant decrease in transfusion requirements with an associated reduced intraoperative blood loss of nearly 45% compared with those in NTXA group (8 vs 37, 619 ml vs 1125 ml, P < 0.05). There were no significant difference in total irrigation fluid between two groups (540 vs 550, p >0.05). Additional, patients in NTXA group showed significant decrease of Hb compared with patients in TXA group (5.2 g/dL vs 3.3 g/dL, P < 0.05), No significant difference were found in hospitalization time between two groups (6.3 vs 7.2 days, P > 0.05). No minor adverse effects associated with use of TXA were noted. CONCLUSIONS: Use of large dose tranexamic acid routinely seems to be effective and safe in reducing allogenic blood transfusion and blood loss in adolescent idiopathic scoliosis surgery.

BDNF-dependent recycling facilitates TrkB translocation to postsynaptic density during LTP via a Rab11-dependent pathway.

Brain-derived neurotrophic factor (BDNF) plays an important role in the activity-dependent regulation of synaptic structure and function via tropomyosin related kinase B (TrkB) receptor activation. However, whether BDNF could regulate TrkB levels at synapse during long-term potentiation (LTP) is still unknown. We show in cultured rat hippocampal neurons that chemical LTP (cLTP) stimuli selectively promote endocytic recycling of BDNF-dependent full-length TrkB (TrkB-FL) receptors, but not isoform T1 (TrkB.T1) receptors, via a Rab11-dependent pathway. Moreover, neuronal-activity-enhanced TrkB-FL recycling could facilitate receptor translocation to postsynaptic density and enhance BDNF-induced extracellular signal-regulated kinase and phosphatidylinositol 3-kinase activation and rat hippocampal neuron survival. Finally, we found that cLTP could stimulate the switch of Rab11 from an inactive to an active form and that GTP-bound Rab11 could enhance the interaction between TrkB-FL and PSD-95. Therefore, the recycling endosome could serve as a reserve pool to supply TrkB-FL receptors for LTP maintenance. These findings provide a mechanistic link between Rab11-dependent endocytic recycling and TrkB modulation of synaptic plasticity.

Autophagy involved in lipopolysaccharide-induced foam cell formation is mediated by adipose differentiation-related protein.

BACKGROUND: Autophagy is an essential process for breaking down macromolecules and aged/damaged cellular organelles to maintain cellular energy balance and cellular nutritional status. The idea that autophagy regulates lipid metabolism is an emerging concept with important implications for atherosclerosis. However, the potential role of autophagy and its relationship with lipid metabolism in foam cell formation remains unclear. In this study, we found that autophagy was involved in the lipopolysaccharide (LPS)-induced the formation of foam cells and was at least partially dependent on adipose differentiation-related protein (ADRP). METHOD: Foam cell formation was evaluated by Oil red O staining. Autophagic activity was determined by immunofluorescence and Western blotting. ADRP gene expression of ADRP was examined by real-time PCR (RT-PCR). The protein expression of ADRP and LC3 was measured using Western blotting analysis. Intracellular cholesterol and triglyceride levels in foam cells were quantitatively measured by enzymatic colorimetric assays. RESULTS: LPS promoted foam cell formation by inducing lipid accumulation in macrophages. The activation of autophagy with rapamycin (Rap) decreased intracellular cholesterol and triglyceride levels, whereas the inhibition of autophagy with 3-methyladenine (3MA) enhanced the accumulation of lipid droplets. Overexpression of ADRP alone increased the formation of foam cells and consequently autophagic activity. In contrast, the inhibitory effects of ADRP activity with siRNA suppressed the activation of autophagy. Taken together, we propose a novel role for ADRP in the regulation of macrophage autophagy during LPS stimulation. CONCLUSION: We defined a new molecular pathway in which LPS-induced foam cell formation is regulated through autophagy. These findings facilitate the understanding of the role of autophagy in the development of atherosclerosis.

Application of matrix-assisted laser desorption ionization time-of-flight mass spectrometry in the screening of vanA-positive Enterococcus faecium.

In order to evaluate a rapid matrix-assisted laser desorption ionization-time of flight mass spectrometry (MAIDI-TOF MS) assay in screening vancomycin-resistant Enterococcus faecium, a total of 150 E. faecium clinical strains were studied, including 60 vancomycin-resistant E. faecium (VREF) isolates and 90 vancomycin-susceptible (VSEF) strains. Vancomycin resistance genes were detected by sequencing. E. faecium were identified by MALDI-TOF MS. A genetic algorithm model with ClinProTools software was generated using spectra of 30 VREF isolates and 30 VSEF isolates. Using this model, 90 test isolates were discriminated between VREF and VSEF. The results showed that all sixty VREF isolates carried the vanA gene. The performance of VREF detection by the genetic algorithm model of MALDI-TOF MS compared to the sequencing method was sensitivity = 80%, specificity = 90%, false positive rate =10%, false negative rate =10%, positive predictive value = 80%, negative predictive value= 90%. MALDI-TOF MS can be used as a screening test for discrimination between vanA-positive E. faecium and vanA-negative E. faecium.