Enterotoxigenic Escherichia coli heat labile enterotoxin affects neutrophil effector functions via cAMP/PKA/ERK signaling.

Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrheal illness in humans and animals, induced by enterotoxins produced by these pathogens. Despite the crucial role of neutrophils in combatting bacterial infections, our understanding of how enterotoxins impact neutrophil function is limited. To address this knowledge gap, we used heat-labile enterotoxin (LT) and heat-stable enterotoxin a (STa) to investigate their impact on the effector functions of neutrophils. Our study reveals that pSTa does not exert any discernible effect on the function of neutrophils. In contrast, LT altered the migration and phagocytosis of neutrophils and induced the production of inflammatory factors via activation of cAMP/PKA and ERK1/2 signaling. LT also attenuated the release of neutrophil extracellular traps by neutrophils via the PKA signaling pathway. Our findings provide novel insights into the impact of LT on neutrophil function, shedding light on the underlying mechanisms that govern its immunoregulatory effects. This might help ETEC in subverting the immune system and establishing infection.

Update on new trend and progress of the mechanism of polycyclic aromatic hydrocarbon biodegradation by Rhodococcus, based on the new understanding of relevant theories: a review.

Rapid industrial and societal developments have led to substantial increases in the use and exploitation of petroleum, and petroleum hydrocarbon pollution has become a serious threat to human health and the environment. Polycyclic aromatic hydrocarbons (PAHs) are primary components of petroleum hydrocarbons. In recent years, microbial remediation of PAHs pollution has been regarded as the most promising and cost-effective treatment measure because of its low cost, robust efficacy, and lack of secondary pollution. Rhodococcus bacteria are regarded as one of main microorganisms that can effectively degrade PAHs because of their wide distribution, broad degradation spectrum, and network-like evolution of degradation gene clusters. In this review, we focus on the biological characteristics of Rhodococcus; current trends in PAHs degradation based on knowledge maps; and the cellular structural, biochemical, and enzymatic basis of degradation mechanisms, along with whole genome and transcriptional regulation. These research advances provide clues for the prospects of Rhodococcus-based applications in environmental protection.

Yeast polysaccharide mitigated oxidative injury in broilers induced by mixed mycotoxins via regulating intestinal mucosal oxidative stress and hepatic metabolic enzymes.

This study was aimed to investigate the effects of yeast polysaccharides (YPS) on growth performance, intestinal health, and aflatoxin metabolism in livers of broilers fed diets naturally contaminated with mixed mycotoxins (MYCO). A total of 480 one-day-old Arbor Acre male broilers were randomly allocated into a 2 × 3 factorial arrangement of treatments (8 replicates with 10 birds per replicate) for 6 wk to assess the effects of 3 levels of YPS (0, 1, or 2 g/kg) on the broilers fed diets contaminated with or without MYCO (95 µg/kg aflatoxin B1, 1.5 mg/kg deoxynivalenol, and 490 µg/kg zearalenone). Results showed that mycotoxins contaminated diets led to significant increments in serum malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, mRNA expressions of TLR4 and 4EBP1 associated with oxidative stress, mRNA expressions of CYP1A1, CYP1A2, CYP2A6, and CYP3A4 associated with hepatic phase Ⅰ metabolizing enzymes, mRNA expressions of p53 associated with hepatic mitochondrial apoptosis, and AFB1 residues in the liver (P < 0.05); meanwhile dietary MYCO decreased the jejunal villus height (VH), villus height/crypt depth (VH/CD), the activity of serum total antioxidant capacity (T-AOC), mRNA expressions of jejunal HIF-1α, HMOX, and XDH associated with oxidative stress, mRNA expressions of jejunal CLDN1, ZO1, and ZO2, and mRNA expression of GST associated with hepatic phase Ⅱ metabolizing enzymes of broilers (P < 0.05). Notably, the adverse effects induced by MYCO on broilers were mitigated by supplementation with YPS. Dietary YPS supplementation reduced the concentrations of serum MDA and 8-OHdG, jejunal CD, mRNA expression of jejunal TLR2, and 4EBP1, hepatic CYP1A2, and p53, and the AFB1 residues in the liver (P < 0.05), and elevated the serum T-AOC and SOD, jejunal VH, and VH/CD, and mRNA expression of jejunal XDH, hepatic GST of broilers (P < 0.05). There were significant interactions between MYCO and YPS levels on the growth performance (BW, ADFI, ADG, and F/G) at d 1 to 21, d 22 to 42, and d 1 to 42, serum GSH-Px activity, and mRNA expression of jejunal CLDN2 and hepatic ras of broilers (P < 0.05). In contrast with MYCO group, the addition of YPS increased BW, ADFI, and ADG, the serum GSH-Px activity (14.31%-46.92%), mRNA levels of jejunal CLDN2 (94.39%-103.02%), decreased F/G, and mRNA levels of hepatic ras (57.83%-63.62%) of broilers (P < 0.05). In conclusion, dietary supplements with YPS protected broilers from mixed mycotoxins toxicities meanwhile keeping normal performance of broilers, presumably via reducing intestinal oxidative stress, protecting intestinal structural integrity, and improving hepatic metabolic enzymes to minimize the AFB1 residue in the liver and enhance the performance of broilers.

The Role of S100A6 in Human Diseases: Molecular Mechanisms and Therapeutic Potential.

S100A6, also known as calcyclin, is a low-molecular-weight Ca2+-binding protein from the S100 family that contains two EF-hands. S100A6 is expressed in a variety of mammalian cells and tissues. It is also expressed in lung, colorectal, pancreatic, and liver cancers, as well as other cancers such as melanoma. S100A6 has many molecular functions related to cell proliferation, the cell cycle, cell differentiation, and the cytoskeleton. It is not only involved in tumor invasion, proliferation, and migration, but also the pathogenesis of other non-neoplastic diseases. In this review, we focus on the molecular mechanisms and potential therapeutic targets of S100A6 in tumors, nervous system diseases, leukemia, endometriosis, cardiovascular disease, osteoarthritis, and other related diseases.

Synthesis of Isothiocyanates from Primary Amines via Visible-Light Photocatalysis.

A photocatalyzed, efficient, and mild approach for the synthesis of various substituted isothiocyanates from amine and carbon disulfide was reported in this work. This approach expands the scope of photocatalytic applications and provides a new method for the preparation of aliphatic and aromatic isothiocyanates, which are significant organic building blocks and biological diagnostic markers.

Genome-wide association analysis of resistance to frogeye leaf spot China race 7 in soybean based on high-throughput sequencing.

KEY MESSAGE: FLS is a disease that causes severe yield reduction in soybean. In this study, four genes (Glyma.16G176800, Glyma.16G177300, Glyma.16G177400 and Glyma.16G182300) were tentatively confirmed to play an important role in the resistance of soybean to FLS race 7. Frogeye leaf spot (FLS) causes severe yield loss in soybean and has been found in several countries worldwide. Therefore, it is necessary to select and utilize FLS-resistant varieties for the management of FLS. In the present study, 335 representative soybean materials were assessed for partial resistance to FLS race 7. Quantitative trait nucleotide (QTN) and FLS race 7 candidate genes were identified using genome-wide association analysis (GWAS) based on a site-specific amplified fragment sequencing (SLAF-seq) approach. A total of 23,156 single-nucleotide polymorphisms (SNPs) were used to evaluate the level of linkage disequilibrium with a minor allele frequency ≥ 5 and deletion data < 3%. These SNPs covered about 947.01 MBP, nearly 86.09% of the entire soybean genome. In addition, a compressed mixed linear model was utilized to identify association signals for partial resistance to FLS race 7. A total of 15 QTNs associated with resistance were found to be novel for FLS race 7 resistance. A total of 217 candidate genes located in the 200-kb genomic region of these peak SNPs were identified. Based on gene association analysis, qRT-PCR, haplotype analysis and virus-induced gene silencing (VIGS) systems were used to further verify candidate genes Glyma.16G176800, Glyma.16G177300, Glyma.16G177400 and Glyma.16G182300. This indicates that these four candidate genes may participate in FLS race 7 resistance responses.

Pseudorabies virus-induced expression and antiviral activity of type I or type III interferon depend on the type of infected epithelial cell.

Type I and III Interferons (IFNs) are the initial antiviral cytokines produced in response to virus infection. These IFNs in turn bind to their respective receptors, trigger JAK-STAT signaling and induce the expression of IFN-stimulated genes (ISGs) to engage antiviral functions. Unlike the receptor for type I IFNs, which is broadly expressed, the expression of the type III IFN receptor is mainly confined to epithelial cells that line mucosal surfaces. Accumulating evidence has shown that type III IFNs may play a unique role in protecting mucosal surfaces against viral challenges. The porcine alphaherpesvirus pseudorabies virus (PRV) causes huge economic losses to the pig industry worldwide. PRV first replicates in the respiratory tract, followed by spread via neurons and via lymph and blood vessels to the central nervous system and internal organs, e.g. the kidney, lungs and intestinal tract. In this study, we investigate whether PRV triggers the expression of type I and III IFNs and whether these IFNs exert antiviral activity against PRV in different porcine epithelial cells: porcine kidney epithelial cells (PK-15), primary respiratory epithelial cells (PoREC) and intestinal porcine epithelial cells (IPEC-J2). We show that PRV triggers a multiplicity of infection-dependent type I IFN response and a prominent III IFN response in PK-15 cells, a multiplicity of infection-dependent expression of both types of IFN in IPEC-J2 cells and virtually no expression of either IFN in PoREC. Pretreatment of the different cell types with equal amounts of porcine IFN-λ3 (type III IFN) or porcine IFN-α (type I IFN) showed that IFN-α, but not IFN-λ3, suppressed PRV replication and spread in PK-15 cells, whereas the opposite was observed in IPEC-J2 cells and both types of IFN showed anti-PRV activity in PoREC cells, although the antiviral activity of IFN-α was more potent than that of IFN-λ3 in the latter cell type. In conclusion, the current data show that PRV-induced type I and III IFN responses and their antiviral activity depend to a large extent on the epithelial cell type used, and for the first time show that type III IFN displays antiviral activity against PRV in epithelial cells from the respiratory and particularly the intestinal tract.

Lipase-Catalyzed Phospha-Michael Addition Reactions under Mild Conditions.

Organophosphorus compounds are the core structure of many active natural products. The synthesis of these compounds is generally achieved by metal catalysis requiring specifically functionalized substrates or harsh conditions. Herein, we disclose the phospha-Michael addition reaction of biphenyphosphine oxide with various substituted ß-nitrostyrenes or benzylidene malononitriles. This biocatalytic strategy provides a direct route for the synthesis of C-P bonds with good functional group compatibility and simple and practical operation. Under the optimal conditions (styrene (0.5 mmol), biphenyphosphine oxide (0.5 mmol), Novozym 435 (300 U), and EtOH (1 mL)), lipase leads to the formation of organophosphorus compounds in yields up to 94% at room temperature. Furthermore, we confirm the role of the catalytic triad of lipase in this phospha-Michael addition reaction. This new biocatalytic system will have broad applications in organic synthesis.

Weighted gene co-expression network analysis identifies genes related to HG Type 0 resistance and verification of hub gene GmHg1.

Introduction: The soybean cyst nematode (SCN) is a major disease in soybean production thatseriously affects soybean yield. At present, there are no studies on weighted geneco-expression network analysis (WGCNA) related to SCN resistance. Methods: Here, transcriptome data from 36 soybean roots under SCN HG Type 0 (race 3) stresswere used in WGCNA to identify significant modules. Results and Discussion: A total of 10,000 differentially expressed genes and 21 modules were identified, of which the module most related to SCN was turquoise. In addition, the hub gene GmHg1 with high connectivity was selected, and its function was verified. GmHg1 encodes serine/threonine protein kinase (PK), and the expression of GmHg1 in SCN-resistant cultivars ('Dongnong L-204') and SCN-susceptible cultivars ('Heinong 37') increased significantly after HG Type 0 stress. Soybean plants transformed with GmHg1-OX had significantly increased SCN resistance. In contrast, the GmHg1-RNAi transgenic soybean plants significantly reduced SCN resistance. In transgenic materials, the expression patterns of 11 genes with the same expression trend as the GmHg1 gene in the 'turquoise module' were analyzed. Analysis showed that 11genes were co-expressed with GmHg1, which may be involved in the process of soybean resistance to SCN. Our work provides a new direction for studying the Molecular mechanism of soybean resistance to SCN.

miR-522 regulates cell proliferation, migration, invasion capacities and acts as a potential biomarker to predict prognosis in triple-negative breast cancer.

This study was designed to explore the cell functions and prognostic significance of miR-522 in triple-negative breast cancer. The expression levels of miR-522 in triple-negative breast cancer tissues and cell lines were detected by quantitative real-time PCR analysis. Kaplan-Meier curve and Cox regression analysis were used to investigate the relationship between miR-522 expression and prognosis of patients, and to evaluate the possibility of miR-522 as a potential indicator for predicting the prognosis of triple-negative breast cancer. The CCK-8 and transwell assays were used to assess cell proliferation, migration, and invasion abilities. The expression of miR-522 in triple-negative breast cancer tissues was significantly higher than that in adjacent tissues and its high expression was closely associated with the high incidence of lymph node metastasis, advanced TNM stage, and BRCA1/2 mutation status. High expression of miR-522 is correlated with poor overall survival in patients with triple-negative breast cancer. Besides, functional studies in two triple-negative breast cancer cell lines showed that overexpression of miR-522 significantly promoted cell proliferation, migration, and invasion in vitro. BRCA1 was a potential direct target of miR-522. Our findings indicated that miR-522 was highly expressed in triple-negative breast cancer and was associated with poor prognosis of patients. The upregulation of miR-522 accelerated the progression of triple-negative breast cancer by targeting BRCA1. Therefore, miR-522 provides valuable information for the development of prevention and treatment strategies.

Transcriptional Profiling of Aflatoxin B1-Induced Oxidative Stress and Inflammatory Response in Macrophages.

Aflatoxin B1 (AFB1) is a highly toxic mycotoxin that causes severe suppression of the immune system of humans and animals, as well as enhances reactive oxygen species (ROS) formation, causing oxidative damage. However, the mechanisms underlying the ROS formation and immunotoxicity of AFB1 are poorly understood. This study used the mouse macrophage RAW264.7 cell line and whole-transcriptome sequencing (RNA-Seq) technology to address this knowledge-gap. The results show that AFB1 induced the decrease of cell viability in a dose- and time-dependent manner. AFB1 also significantly increased intracellular productions of ROS and malondialdehyde and decreased glutathione levels. These changes correlated with increased mRNA expression of NOS2, TNF-α and CXCL2 and decreased expression of CD86. In total, 783 differentially expressed genes (DEGs) were identified via RNA-Seq technology. KEGG analysis of the oxidative phosphorylation pathway revealed that mRNA levels of ND1, ND2, ND3, ND4, ND4L, ND5, ND6, Cyt b, COX2, ATPeF0A and ATPeF08 were higher in AFB1-treated cells than control cells, whereas 14 DEGs were downregulated in the AFB1 group. Furthermore, seven immune regulatory pathways mediated by oxidative stress were identified by KEGG analysis. Altogether, these data suggest that AFB1 induces oxidative stress in macrophages via affecting the respiratory chain, which leads to the activation of several signaling pathways related to the inflammatory response.

ERK5 negatively regulates Kruppel-like factor 4 and promotes osteogenic lineage cell proliferation in response to MEK5 overexpression or fluid shear stress.

Aim of the study: Fluid shear stress (FSS) plays a critical role in osteoblast proliferation via extracellular signal-regulated kinase 5 (ERK5). Kruppel-like factor 4 (KLF4) knockout robustly enhances bone formation due to increased osteoblast differentiation and mineralization. However, the effect of KLF4 on osteoblast proliferation is unresolved. Therefore, the aim of our study was to investigate the effect of KLF4 on osteogenic lineage cell proliferation and the relationship between KLF4 and ERK5. Materials and methods: MC3T3-E1 cells were treated with FSS and/or KLF4 siRNA, cell viability was accessed by Edu labeling and CCK-8 assay, and proliferative gene expression were assessed by PCR array. Bone marrow stromal cells (BMSCs) were infected with adenovirus expressing KLF4 and/or constitutively active MEK5, cell viability was evaluated using crystal violet staining, colony formation assay, and cell WST1 assay. The levels of KLF4 and ERK5 phosphorylation were identified through qRT-PCR and western blot, respectively. Results: KLF4 expression was significantly down-regulated by FSS exposure, however, this was reversed by ERK5 siRNA. KLF4 overexpression inhibited colony formation efficiency and cell viability in BMSCs. Adenoviruses expressing constitutively active MEK5 increased ERK5 phosphorylation, which inhibited KLF4 expression, and promoted BMSC proliferation. FSS-induced osteoblast proliferation also involved elevation of Cyclin B2 and Cdc14b as well as repressed expression of P27. Conclusions: KLF4 negatively regulates osteogenic lineage cell proliferation, and ERK5 negatively regulates KLF4 expression and promotes osteogenic lineage cell proliferation.

Hypoxia-responsive miR-141-3p is involved in the progression of breast cancer via mediating the HMGB1/HIF-1α signaling pathway.

BACKGROUND: Hypoxia-responsive miRs have been frequently reported in the growth of various malignant tumors. The present study aimed to investigate whether hypoxia-responsive miR-141-3p was implicated in the pathogenesis of breast cancer via mediating the high-mobility group box protein 1 (HMGB1)/hypoxia-inducible factor (HIF)-1α signaling pathway. MATERIALS AND METHODS: miRs expression profiling was filtrated by miR microarray assays. Gene and protein expression levels, respectively, were examined by a quantitative reverse transcriptase-polymerase chaion reaction and western blotting. Cell migration and invasion were analyzed using a transwell assay. Cell growth was determined using nude-mouse transplanted tumor experiments. RESULTS: miR-141-3p was observed as a hypoxia-responsive miR in breast cancer. miR-141-3p was down-regulated in breast cancer specimens and could serve as an independent prognostic factor for predicting overall survival in breast cancer patients. In addition, the overexpression of miR-141-3p could inhibit hypoxia-induced cell migration and impede human breast cancer MDA-MB-231 cell growth in vivo. Mechanistically, the hypoxia-related HMGB1/HIF-1α signaling pathway might be a possible target of miR-141-3p with respect to preventing the development of breast cancer. CONCLUSIONS: Our finding provides a new mechanism by which miR-141-3p could prevent hypoxia-induced breast tumorigenesis via post-transcriptional repression of the HMGB1/HIF-1α signaling pathway.

[Anterior versus posterior decompression for the treatment of thoracolumbar fractures with spinal cord injury:a Meta-analysis].

OBJECTIVE: To systematically evaluate the efficacy and safety of anterior decompression and posterior decompression in the treatment of thoracolumbar fractures with spinal cord injury, so as to provide a good scientific basis for more effective treatment of thoracolumbar fractures with spinal cord injury. METHODS: A clinical data about comparative study of anterior decompression and posterior decompression in the treatment of thoracolumbar fractures with spinal cord injury was searched and collected. The databases of Pubmed, Embase, Cochrane Library, CNKI, CBM, Wanfang Medical Network were searched by computer. Artificially collected journals included Spine, European Spine Journal, The Journal of Bone and Joint Surgery. Two spine surgeons independently screened the literature according to established inclusion and exclusion criteria and assessed the quality of the included studies. Meta-analysis was performed on the data using Review Manager 5.3 software, the indicators included operative time, intraoperative blood loss, postoperative tactile score, postoperative motor score, postoperative vertebral height, hospitalization time, neurological function recovery, efficiency of treatment, postoperative complications. RESULTS: Fifteen randomized controlled trials (RCTs) were enrolled in a total of 1 360 patients, including 680 anterior decompression and 680 posterior decompression. The results of Meta-analysis showed that the anterior decompression group had longer operation time [MD=80.09, 95% CI(36.83, 123.34), P=0.000 3], more intraoperative blood loss [MD=225.21, 95%CI(171.07, 279.35), P<0.000 01], longer hospitalization time [MD=2.31, 95% CI(0.32, 4.31), P=0.02]. And the postoperative tactile score [MD=13.39, 95% CI(9.86, 16.92), P<0.000 01], postoperative motor score [MD=13.15, 95% CI(7.02, 19.29), P<0.000 1], vertebral height [MD=1.36, 95% CI(0.79, 1.92), P<0.000 01] in anterior decompression were higher than that in posterior decompression. There was no statistically significant differences in the efficacy of treatment [OR=1.14, 95% CI(0.56, 2.31), P=0.72], neurological recovery [OR=0.87, 95% CI(0.57, 1.33), P=0.52] between two groups. CONCLUSIONS: Compared with posterior decompression, the anterior decompression has the advantages of longer operating time, more intraoperative blood loss, longer hospitalization time, higher postoperative tactile score, higher postoperative motor score, and higher injury vertebral height, But there was no significant difference in the treatment efficiency and nerve function recovery between two groups.

[High-affinity glutamate transporters and chronic pain].

Glutamate serves as a major excitatory neurotransmitter in the mammalian central nervous system and is stored in synaptic cleft by an uptake system that is dependent on the high-affinity glutamate transporters (ETTAs), which locate in the plasma membrane of glial cells and neurons. ETTAs can rapidly terminate the action of glutamate and maintain its normal physiological functions. If the content or function of glutamate transporters is abnormal, it can result in many physiological dysfunctions. Studies have demonstrated that high-affinity glutamate transporters play an important role in the development of chronic pain, which might be a new therapeutic target for the pain.

Clinical efficacy and safety of limited internal fixation combined with external fixation for Pilon fracture: A systematic review and meta-analysis.

PURPOSE: To compare the clinical efficacy and complications of limited internal fixation combined with external fixation (LIFEF) and open reduction and internal fixation (ORIF) in the treatment of Pilon fracture. METHODS: We searched databases including Pubmed, Embase, Web of science, Cochrane Library and China Biology Medicine disc for the studies comparing clinical efficacy and complications of LIFEF and ORIF in the treatment of Pilon fracture. The clinical efficacy was evaluated by the rate of nonunion, malunion/delayed union and the excellent/good rate assessed by Mazur ankle score. The complications including infections and arthritis symptoms after surgery were also investigated. RESULTS: Nine trials including 498 pilon fractures of 494 patients were identified. The meta-analysis found no significant differences in nonunion rate (RR = 1.60, 95% CI: 0.66 to 3.86, p = 0.30), and the excellent/good rate (RR = 0.95, 95% CI: 0.86 to 1.04, p = 0.28) between LIFEF group and ORIF group. For assessment of infections, there were significant differences in the rate of deep infection (RR = 2.18, 95% CI: 1.34 to 3.55, p = 0.002), and the rate of arthritis (RR = 1.26, 95% CI: 1.03 to 1.53, p = 0.02) between LIFEF group and ORIF group. CONCLUSION: LIFEF has similar effect as ORIF in the treatment of pilon fractures, however, LIFEF group has significantly higher risk of complications than ORIF group does. So LIFEF is not recommended in the treatment of pilon fracture.

[Development of Automatic Diagnosis and Evaluation System for ECG Recorder].

ECG Recorder's automatic diagnosis function is uneven, it brings a lot of inconvenience to clinicians in the diagnosis and treatment. We developed the automatic diagnosis and evaluation system for ECG recorder based on data platform in General Hospital of PLA, in order to evaluate the automatic diagnosis function of ECG recorder and improve the level of automatic diagnosis, and through a large number of data evaluation results, to provides the standard basis of ECG recorder's automatic diagnosis.

Narrow Intercondylar Notch and Anterior Cruciate Ligament Injury in Female Nonathletes with Knee Osteoarthritis Aged 41-65 Years in Plateau Region.

BACKGROUND: Few data are available concerning intercondylar notch dimensions in female nonathletes with knee osteoarthritis (OA) in plateau region. The aim of this study was to assess the relation of intercondylar notch morphology to anterior cruciate ligament (ACL) injuries in female nonathletes with knee OA aged 41-65 years from the Chinese Loess Plateau. METHODS: The study was conducted on 330 patients with ACL injury (aged 31-65 years; 159 males, 171 females), 141 patients with OA (aged 31-65 years; 59 males, 82 females), and 89 female healthy controls (aged 41-65 years), and this evaluation included identifying the distribution of patients with OA or ACL injury and measuring the intercondylar notch width indexes (NWIs). RESULTS: There was a significant rising trend in patients with OA (the Kellgren and Lawrence grade = 3) with ACL injury (OA-S + ACL) aged 41-65 years, especially in females. We found that the notches of OA-S + ACL had a smaller NWI compared with control and OA without ACL injury (OA-S-only, P = 0.000, 95% confidence interval [CI] = -0.059--0.030; P = 0.000, 95% CI = -0.049--0.016). A similar trend was found in notch shape index (NSI), but not in notch depth index and the cross-sectional area. The cutoff of NWI and NSI value was 0.26, and 0.65, and area under the receiver operating characteristic curve was 0.82, and 0.79, respectively. Further study displayed a significant correlation between a reduced NWI and NSI and OA-S + ACL (P = 0.000, χ2 = 14.012; P = 0.000, χ2 = 14.286). CONCLUSION: A narrower intercondylar notch and a plateau environment are risk factors of predisposing female nonathletes with knee OA to ACL injury aged 41-65 years.

[CHANGES OF SEMAPHORIN 3A EXPRESSION IN HEALING OF TIBIA FRACTURE AFTER TRAUMATIC BRAIN INJURY].

OBJECTIVE: To investigate the mechanism of Semaphorin 3A (Sema3A) in fracture healing after nerve injury by observing the expression of Sema3A in the tibia fracture healing after traumatic brain injury (TBI). METHODS: A total of 192 Wistar female rats, 8-10 weeks old and weighing 220-250 g, were randomly divided into tibia fracture group (group A, n=48), TBI group (group B, n=48), TBI with tibia fracture group (group C, n=48), and control group (group D, n=48). The tibia fracture model was established at the right side of group A; TBI model was made in group B by the improved Feeney method; the TBI and tibia fracture model was made in group C; no treatment was given in group D. The tissue samples were respectively collected at 3, 5, 7, 14, 21, and 28 days after operation; HE staining, immunohistochemistry staining, and Western blot method were used for the location and quantitative detection of Sema3A in callus tissue. RESULTS: HE staining showed that no obvious changes were observed at each time point in groups B and D. At 3 and 5 days, there was no obvious callus growth at fracture site with inflammatory cells and fibrous tissue filling in groups A and C. At 7 and 14 days, fibrous tissue grew from periosteum to fracture site in groups A and C; the proliferation of chondrocytes in exterior periosteum gradually formed osteoid callus at fracture site in groups A and C. The chondrocyte had bigger size, looser arrangement, and more osteoid in group C than group A. Group B had disorder periosteum, slight subperiosteal bone hyperplasia, and no obvious change of bone trabecula in group B when compared with group D. At 21 and 28 days, cartilage callus was gradually replaced by new bone trabecula in groups A and C. Group C had loose arrange, disorder structure, and low density of bone trabecula, big callus area and few chondrocyte and osteoid when compared with group A; group B was similar to Group D. Immunohistochemistry staining showed that Sema3A expression in chondrocytes in group C was higher than that in group A, particularly at 7, 14, and 21 day. Sema3A was significantly higher in osteoblasts of new bone trabecula in group A than group C, especially at 14 and 21 days (P<0.05). Western blot results showed that the Sema3A had the same expression trend during fracture healing in groups A and C. However, the expression of Sema3A protein was significantly higher in group C than group A (P<0.05) and in group B than group D (P<0.05) at 7, 14, 21, and 28 days. CONCLUSIONS: Abnormal expression of Sema3A may play a role in fracture healing after nerve injury by promoting the chondrocytes proliferation and reducing the distribution of sensory nerve fibers and osteoblast differentiation.

Efficacy and safety of etoricoxib compared with NSAIDs in acute gout: a systematic review and a meta-analysis.

The aim is to study the efficacy and safety of etoricoxib in the treatment of acute gout, as compared with non-steroidal anti-inflammatory drugs (NSAIDs). We conducted a computerized search of electronic databases: PubMed, EMBASE, Web of Science, China Biology Medicine disc, and Cochrane Library. The search terms were as follows: gout arthritis, tophus, etoricoxib, indometacin naproxen, diclofenac, and NSAIDs. Articles were searched from 1983 until August 2014. A manual search of peer-reviewed English documents was performed by cross-checking the bibliographies of selected studies. These trials reported pain relief as the primary outcome. Tenderness, swelling, patients' global assessments of response to treatment, and investigators' global assessments of response to treatment were reported as the secondary outcomes. All adverse events were recorded for safety assessment. Six trials including 851 patients were identified. Both etoricoxib and NSAIDs had an effect on inflammation and analgesia. Compared with indometacin and diclofenac, etoricoxib had a lower incidence of adverse events. Etoricoxib 120 mg administered orally once daily has the same efficacy on acute gout as indometacin and diclofenac. Etoricoxib is tolerated better by patients than NSAIDs such as indometacin and diclofenac.