Prevalence and drug resistance of Escherichia coli among patients with orthopaedic surgical site infections in China: A systematic review and meta-analysis.

To summarize current prevalence and drug resistance rate of Escherichia coli (E. coli) among orthopaedic surgical site infections (SSIs) in China from English and Chinese language sources. Online databases were searched to collect related researches. A meta-analysis was performed to analyse prevalence and 95 % confidence interval (CI) of E. coli among patients with orthopedic surgical site infections. Meta-regression analysis was used to investigate the difference in the prevalence and antimicrobial resistance of E. coli among different subgroups. A total of 52 studies were enrolled into our meta-analysis, with a total of 31,285 strains isolated. The overall E. coli prevalence was 13.4 % (95 % CI 11.6-15.5). Study design (R2 = 8.98) and sample size (R2 = 10.95) might be potential sources of heterogeneity and there were no significant differences in risk of bias (R2 = 0.28), study time (R2 < 0.01), region (R2 = 2.46) and hospital level (R2 = 1.42). E. coli resistance were reported in 43 of the 52 papers. Antimicrobial resistance of E. coli to Ampicillin [87.9 % (95 % CI 83.7-91.1)] before 2015 was higher than that after 2015 [80.3 % (95 % CI 75.0-84.7)] (R2 = 30.93, P = 0.033). While, resistance rate to Cefepime and Amikacin was significantly higher before 2015 (R2 = 17.25 and 6.54, P = 0.043 and 0.048), i.e., 46.4 % (36.3-56.9), 19.9 % (13.8-27.7) and 29.1 % (19.4-41.2), 8.6 % (4.4-16.2) in 2015 and after. It is necessary to carry out long-term monitoring to understand the actual prevalence and antimicrobial resistance of E. coli to develop appropriate health care mechanisms.

Mechanical properties evaluation of metacarpophalangeal joint prosthesis with new titanium-nickel memory alloy: a cadaver study.

OBJECTIVE: Ni-Ti memory alloys are unusual materials for hard-tissue replacement because of their unique superelasticity, good biocompatibility, high strength, low specific gravity, low magnetism, wear resistance, corrosion resistance and fatigue resistance. The current study aims to evaluate its mechanical properties and provide biomechanical basis for the clinical application of the prosthesis. METHODS: Ten adult metacarpophalangeal joint specimens were randomly divided into a prosthesis group (n = 5, underwent metacarpophalangeal joint prosthesis) and a control group (n = 5, underwent sham operation). Firstly, the axial compression strength was tested with BOSE material testing machine to evaluate its biomechanical strength. Secondly, these specimens were tested for strain changes using BOSE material testing machine and GOM non-contact optical strain measurement system to evaluate the stress changes. Thirdly, fatigue test was performed between groups. Lastly, the mechanical wear of the metacarpophalangeal joint prosthesis was tested with ETK5510 material testing machine to study its mechanical properties. RESULTS: Axial compression stiffness in the prosthesis group was greater than that in the control group in terms of 30 ° and 60 ° flexion positions (P < 0.05). There was no statistically significant difference between two groups with regards to axial compression stiffness and stress change test (P > 0.05). In the fatigue wear test, the mean mass loss in the prosthesis group's prosthesis was 17.2 mg and 17.619 mm3, respectively. The mean volume wear rate was 0.12%. There was no statistically significant difference in the maximum pull-out force of the metacarpal, phalangeal, and polymer polyethylene pads between the prosthesis group and the control group specimens. CONCLUSIONS: Ni-Ti memory alloy metacarpophalangeal joint prosthesis conforms to the biomechanical characteristics of metacarpophalangeal joints without implants, and the fatigue strength can fully meet the needs of metacarpophalangeal joint activities after joint replacement.

Pmepa1 knockdown alleviates SpA-induced pyroptosis and osteogenic differentiation inhibition of hBMSCs via p38MAPK/NLRP3 axis.

BACKGROUND: Osteomyelitis is a refractory bone infectious disease, which usually results in progressive bone destruction and bone loss. The invasion of pathogens and subsequent inflammatory response could damage bone marrow mesenchymal stem cells (BMSCs) and inhibit osteogenic differentiation, and finally aggravate uncontrolled bone remodeling in osteomyelitis by affecting bone formation. Exploring the mechanisms of BMSCs injury and osteogenic differentiation inhibition may would help us to find potential therapeutic targets. METHOD: Firstly, staphylococcal protein A (SpA)-treated human bone marrow mesenchymal stem cells (hBMSCs) were used to construct cell models of osteomyelitis. Secondly, transcriptome sequencing was performed to screen differentially expressed genes and then verified the expression of target genes. Next, in vitro experiments were conducted to explore the functions and mechanisms of prostate transmembrane protein androgen induced 1 (Pmepa1) in SpA-treated hBMSCs. Finally, the rat model of osteomyelitis was established to provide an auxiliary validation of the in vitro experimental results. RESULTS: We found that SpA treatment induced inflammatory injury and inhibited osteogenic differentiation in hBMSCs, then the transcriptome sequencing and further detection results showed that Pmepa1 was significantly upregulated in this process. Functionally, Pmepa1 knockdown alleviated inflammatory injury and promoted osteogenic differentiation in SpA-treated hBMSCs. Among them, it was demonstrated that Pmepa1 knockdown exerted cytoprotective effects by alleviating pyroptosis of SpA-infected hBMSCs. Furthermore, recovery experiments revealed that Pmepa1 knockdown reversed SpA-mediated adverse effects by downregulating the p38MAPK/NLRP3 axis. Finally, the detection results of rat femoral osteomyelitis showed that the expression of Pmepa1 was up-regulated, and the expression trends of other indicators including p38MAPK, NLRP3, and caspase-1 were also consistent with the in vitro model. CONCLUSION: Pmepa1 knockdown alleviates SpA-induced pyroptosis and inhibition of osteogenic differentiation in hBMSCs by downregulating p38MAPK/NLRP3 signaling axis. Modulating the expression of Pmepa1 may be a potential strategy to ameliorate osteomyelitis.

Identification of two novel lipid metabolism-related long non-coding RNAs (SNHG17 and LINC00837) as potential signatures for osteosarcoma prognosis and precise treatment.

OBJECTIVE: Dysregulated lipid metabolism enhances the development and advancement of many cancers, including osteosarcoma (OS); however, the underlying mechanisms are still largely unknown. Therefore, this investigation aimed to elucidate novel potential lipid metabolism-related long non-coding RNAs (lncRNAs) that regulate OS development and provide novel signatures for its prognosis and precise treatment. MATERIALS AND METHODS: The GEO datasets (GSE12865 and GSE16091) were downloaded and analyzed using R software packages. Immunohistochemistry (IHC) was used to evaluate protein levels in OS tissues while real-time qPCR was used to measure lncRNA levels, and MTT assays were used to assess OS cell viability. RESULTS: Two lipid metabolism-associated lncRNAs (LM-lncRNAs), small nucleolar RNA host gene 17 (SNHG17) and LINC00837, were identified as efficient and independent prognostic indicators for OS. In addition, further experiments confirmed that SNHG17 and LINC00837 were significantly elevated in OS tissues and cells than para-cancerous counterparts. Knockdown of SNHG17 and LINC00837 synergistically suppressed the viability of OS cells, whereas overexpression of the two lncRNAs promoted OS cell proliferation. Moreover, bioinformatics analysis was conducted to construct six novel SNHG17-microRNA-mRNA competing endogenous RNA (ceRNA) networks, and three lipid metabolism-associated genes (MIF, VDAC2, and CSNK2A2) were found to be abnormally upregulated in OS tissues, suggesting that they were potential effector genes of SNHG17. CONCLUSION: In summary, SNHG17 and LINC00837 were found to promote OS cell malignancy, suggesting their use as ideal biomarkers for OS prognosis and treatment.

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism.

Osteonecrosis of the femoral head (ONFH) is a common disabling disease. Copper has positive effects on cells that regulate bone metabolism. However, the relationship between copper metabolism (CM) and steroid-induced ONFH (SONFH) remains unclear. The GSE123568 dataset was downloaded from the Gene Expression Omnibus. The differentially expressed CM-related SONFH genes (DE-CMR-SONFHGs) were identified via differential analysis and weighted gene coexpression network analysis (WGCNA). Receiver operating characteristic (ROC) analysis was performed for the predictive accuracy of key genes. Targeting drugs and the copper death-related genes (CDRGs) relevant to key genes were investigated. The bioinformatics results were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Two out of 106 DE-CMR-SONFHGs were identified as key genes (PNP and SLC2A1), which had diagnostic value in distinguishing SONFH from control samples and were related to various immune cell infiltrations. Eleven PMP-targeting drugs and five SLC2A1-targeting drugs were identified. The qRT-PCR, as well as WB, results confirmed the downregulation PNP and SLC2A1 and high expression of the CDRGs DLD, PDHB, and MTF1, which are closely related to these two key genes. In conclusion, PNP and SLC2A1 were identified as key genes related to SONFH and may provide insights for SONFH treatment.

Macrophage migration inhibitory factor (MIF) inhibitor iSO-1 promotes staphylococcal protein A-induced osteogenic differentiation by inhibiting NF-κB signaling pathway.

BACKGROUND: Osteomyelitis is among the most difficult to treat diseases in the field of orthopedics, and there is a lack of effective treatment modalities. Exploring the mechanisms of its development is beneficial for finding molecular targets for treatment. Increasing evidence suggests that macrophage migration inhibitory factor (MIF), as a proinflammatory mediator, is not only involved in various pathophysiological processes of inflammation but also plays an important role in osteogenic differentiation, while its specific regulatory mechanism in osteomyelitis remains unclear. METHODS: In the present study, staphylococcal protein A (SPA)-treated rat bone marrow mesenchymal stem cells (rBMSCs) were used to construct cell models of osteomyelitis. Rat and cell models of osteomyelitis were used to validate the expression levels of MIF, and to further explore the regulatory mechanisms of the MIF inhibitor methyl ester of (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (iSO-1) and MIF knockdown on cell model of osteomyelitis toward osteogenic differentiation. RESULTS: We found that the expression level of MIF was upregulated in rat and cell models of osteomyelitis and subsequently demonstrated by the GSE30119 dataset that the expression level of MIF was also significantly upregulated in patients with osteomyelitis. Furthermore, SPA promotes MIF expression in rBMSCs while inhibiting the expression of osteogenic-related genes such as Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN) and collagen type-1 (COL-1) through activation of the nuclear factor kappa-B (NF-κB) pathway. In vivo, we further demonstrated that local injection of iSO-1 significantly increased the osteogenic activity in rat model of osteomyelitis. Importantly, we also demonstrated that MIF knockdown and the MIF inhibitor iSO-1 reversed the SPA-mediated inhibition of osteogenic differentiation of rBMSCs by inhibiting the activation of the NF-κB pathway, as evidenced by the upregulation of osteogenic-related gene expression and enhanced bone mineralization. CONCLUSION: ISO-1 and MIF knockdown can reverse the SPA-mediated inhibition of osteogenic differentiation in the rBMSCs model of osteomyelitis by inhibiting the NF-κB signaling pathway, providing a potential target for the treatment of osteomyelitis.

Antibiotic-loaded calcium sulfate in clinical treatment of chronic osteomyelitis: a systematic review and meta-analysis.

BACKGROUND: Present work was aimed to gather accessible evidence on the eradication rates and related postoperative complications of antibiotic-loaded calcium sulfate (CS) as an implant in the treatment of chronic osteomyelitis (COM). METHODS: Databases including PubMed, EMBASE, Medline, Ovid and Cochrane library were searched from their dates of initiation until November 2021. Two independent authors scrutinized the relevant studies based on the effectiveness of radical debridement combined with antibiotic-loaded CS for COM; data extraction and quality assessment of the Methodological Index for Non-Randomized Studies (MINORS) criteria were also performed by the authors. In addition, clinical efficacy mainly depended on the evaluation of eradication rates and complications, and all the extracted data are pooled and analyzed by STATA 16.0. RESULTS: A total of 16 studies with 917 patients (920 locations) were recruited, with an overall eradication rate of 92%. Moreover, the overall reoperation rate, overall refracture rate, overall delayed wound healing rate, and the rate of aseptic wound leakage were 9.0%, 2.0%, 20.0%, and 12.0%, respectively. Moreover, the choice of tobramycin-loaded CS or vancomycin combined with gentamicin-loaded CS did not affect the eradication rate, and the incidence of postoperative complications in COM patients (all [Formula: see text]). The general quality of the included studies was fair. CONCLUSIONS: Our meta-analysis indicated that the overall eradication rate of COM treated with antibiotic-loaded CS was 92%. Delayed healing is the most common postoperative complication. The choice of tobramycin-loaded CS or vancomycin combined with gentamicin-loaded CS did not affect the eradication rate and the incidence of postoperative complications in COM patients.

Construction of a circRNA-miRNA-mRNA network based on competitive endogenous RNA reveals the function of circRNAs in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a common primary malignant bone tumour. Growing evidence suggests that circular RNAs (circRNAs) are closely related to the development of tumours. However, the function of circRNAs in OS remains unknown. Here, we aimed to determine the regulatory mechanisms of circRNAs in OS. METHODS: The expression profiles of OS circRNA (GSE96964), microRNA (GSE65071) and mRNA (GSE33382) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed circRNAs, miRNAs and mRNAs in OS. A ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. MRNAs with significant prognostic differences were identified by the TARGET database in the network. Functional and pathway enrichment analyses were performed, and interactions between proteins were predicted using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the possible functions of these differentially expressed circRNAs. RESULTS: A total of 15 downregulated circRNAs, 136 upregulated miRNAs and 52 downregulated mRNAs were identified in OS. Finally, a circRNA-miRNA-mRNA network was constructed in OS based on 14 circRNAs, 24 miRNAs, and 52 mRNAs. GO and KEGG pathway analyses suggested that the mRNAs in the network may be involved in the pathogenesis and progression of OS. Four mRNAs identified by the TARGET database were significantly associated with OS survival prognosis. A circRNA-miRNA-mRNA subnetwork was constructed based on these four mRNAs. CONCLUSION: Our results provide a deeper understanding of the regulatory mechanisms by which circRNAs compete for endogenous RNAs in OS.

Four-corner arthrodesis concentrator of nickel-titanium memory alloy for carpal collapse: a report on 18 cases.

PURPOSE: To evaluate the treatment of carpal collapse using a four-corner arthrodesis concentrator of nickel-titanium memory alloy. METHODS: From August 2006 to August 2010, 18 patients with carpal collapse had scaphoid excision and four-corner (capitate, lunate, triquetrum, and hamate) arthrodesis using a nickel-titanium memory alloy four-corner arthrodesis concentrator. The mean follow-up time was 30 months (range, 12-48). Various wrist parameters, including grip strength, wrist motion, and degree of pain were recorded and compared before and after surgery. RESULTS: The average fusion time was 2.3 months (range, 2-4). Neither nonunion nor wound infection was found in any of the patients. At one year follow-up, the grip strength had reached 80% of that of the healthy side, whereas the range of motion was greater than 50% of the contralateral side. After the surgery, the mean pain scores were improved. CONCLUSIONS: Four-corner arthrodesis using a nickel-titanium memory alloy four-corner arthrodesis concentrator effectively treated carpal collapse and preserved most wrist function.

Four-corner arthrodesis concentrator of Ni-Ti memory alloy for carpal collapse.

OBJECTIVE: To evaluate the treatment outcomes of a four-corner arthrodesis concentrator of Ni-Ti memory alloy for carpal collapse. METHODS: From August 2006 to November 2009, 13 patients with carpal collapse underwent scaphoid excision and four-corner (capitate, lunate, triquetrum and hamate) arthrodesis using a four-corner arthrodesis concentrator of Ni-Ti memory alloy. The mean follow-up time was 26.5 months (range, 7-38 months). Various wrist parameters, including the grip strength, range of wrist movements and degree of pain (visual analogue scales) were recorded and compared before and after surgery. RESULTS: The average fusion time was 2.3 months (range, 2-4 months). Neither non-union nor wound infection was found in any of the patients. By the sixth month postoperatively, the grip strength had reached an average of 32.49 ± 6.21 kg with a range of 22.3-39.7 kg, this being 80.8% of that found on the healthy side. The range of motion reached over 53.0% of that of the healthy side. Preoperatively and at 6 months postoperatively, the mean pain scores were (4.46 ± 1.27) and 1.31 ± 0.95, respectively, when resting (P < 0.05), and 7.00 ± 1.41 and 2.62 ± 1.26, respectively, when weight-bearing (P < 0.05). The mean value of the Krimmer wrist score was 79.2 (range, 64-84). The rate of excellent and fine results was 84.6% (11/13), being excellent in three cases, good in eight and fair in two. CONCLUSION: Four-corner arthrodesis using a four-corner arthrodesis concentrator of Ni-Ti memory alloy is an effective method for treating carpal collapse and preserving most wrist function.