Analysis of PANoptosis-related ceRNA network reveals lncRNA MIR17HG involved in osteogenic differentiation inhibition impaired by tumor necrosis factor-α.

BACKGROUND: Inflammatory cytokines such as Interleukin 1ß(IL1ß), IL6,Tumor Necrosis Factor-α (TNF-α) can inhibit osteoblast differentiation and induce osteoblast apoptosis. PANoptosis, a newly identified type of programmed cell death (PCD), may be influenced by long noncoding RNA (lncRNAs) which play important roles in regulating inflammation. However, the potential role of lncRNAs in inflammation and PANoptosis during osteogenic differentiation remains unclear. This study aimed to investigate the regulatory functions of lncRNAs in inflammation and apoptosis during osteogenic differentiation. METHODS AND RESULTS: High-throughput sequencing was used to identify differentially expressed genes involved in osteoblast differentiation under inflammatory conditions. Two lncRNAs associated with inflammation and PANoptosis during osteogenic differentiation were identified from sequencing data and Gene Expression Omnibus (GEO) databases. Their functionalities were analyzed using diverse bioinformatics methodologies, resulting in the construction of the lncRNA-miRNA-mRNA network. Among these, lncRNA (MIR17HG) showed a high correlation with PANoptosis. Bibliometric methods were employed to collect literature data on PANoptosis, and its components were inferred. PCR and Western Blotting experiments confirmed that lncRNA MIR17HG is related to PANoptosis in osteoblasts during inflammation. CONCLUSIONS: Our data suggest that TNF-α-induced inhibition of osteogenic differentiation and PANoptosis in MC3T3-E1 osteoblasts is associated with MIR17HG. These findings highlight the critical role of MIR17HG in the interplay between inflammation, PANoptosis, and osteogenic differentiation, suggesting potential therapeutic targets for conditions involving impaired bone formation and inflammatory responses.

Diabetes and osteoporosis: a two-sample mendelian randomization study.

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Quercetin as a promising intervention for rat osteoarthritis by decreasing M1-polarized macrophages via blocking the TRPV1-mediated P2X7/NLRP3 signaling pathway.

Osteoarthritis (OA) is characterized by an imbalance between M1 and M2 polarized synovial macrophages. Quercetin has shown protective effects against OA by altering M1/M2-polarized macrophages, but the underlying mechanisms remain unclear. In this study, rat chondrocytes were treated with 10 ng/mL of IL-1ß. To create M1-polarized macrophages in vitro, rat bone marrow-derived macrophages (rBMDMs) were treated with 100 ng/mL LPS. To mimic OA conditions observed in vivo, a co-culture system of chondrocytes and macrophages was established. ATP release assays, immunofluorescence assays, Fluo-4 AM staining, Transwell assays, ELISA assays, and flow cytometry were performed. Male adult Sprague-Dawley (SD) rats were used to create an OA model. Histological analyses, including H&E, and safranin O-fast green staining were performed. Our data showed a quercetin-mediated suppression of calcium ion influx and ATP release, with concurrent downregulation of TRPV1 and P2X7 in the chondrocytes treated with IL-1ß. Activation of TRPV1 abolished the quercetin-mediated effects on calcium ion influx and ATP release in chondrocytes treated with IL-1ß. In the co-culture system, overexpression of P2X7 in macrophages attenuated the quercetin-mediated effects on M1 polarization, migration, and inflammation. Either P2X7 or NLRP3 knockdown attenuated IL-1ß-induced M1/M2 polarization, migration, and inflammation. Moreover, overexpression of TRPV1 reduced the quercetin-mediated suppressive effects on OA by promoting M1/M2-polarized macrophages in vivo. Collectively, our data showed that quercetin-induced suppression of TRPV1 leads to a delay in OA progression by shifting the macrophage polarization from M1 to M2 subtypes via modulation of the P2X7/NLRP3 pathway.

ELP2-NLRP3-GSDMD/GSDME-mediated pyroptosis is induced by TNF-α in MC3T3-E1 cells during osteogenic differentiation.

Tumour necrosis factor-α (TNF-α) is a cytokine involved in systemic inflammation. TNF-α slows down osteogenic differentiation, which may contribute to poor bone development in the inflammatory microenvironment. TNF-α inhibits osteogenic differentiation by activating the JAK-STAT3 pathway, of which Signal transducer and activator of transcription 3 (STAT3)-interacting protein 1 (StIP1, also known as elongator complex protein 2, ELP2) is a key protein in the JAK-STAT3 pathway. We investigated whether and how ELP2 activation mediates the TNF-α-induced pyroptosis during osteoblastic differentiation. Using in vitro cell cultures of preosteoblastic MC3T3-E1 cells, we found that TNF-α exposure causes cell pyroptosis in an inflammatory microenvironment during osteoblastic differentiation. Bioinformatics, protein docking model and co-immunoprecipitation analysis revealed an association between ELP2, STAT3 and NLRP3. Forced ELP2 expression promoted MC3T3-E1 cells pyroptosis, with an increase in the expression of STAT3, NLRP3 inflammasome, GSDMD/GSDME, osteoblast marker genes, and the activity of alkaline phosphatase. In contrast, ELP2 silencing ameliorated MC3T3-E1 cells pyroptosis, and osteogenic differentiation, especially after TNF-α stimulation. The TNF-α-induced cells pyroptosis during osteoblastic differentiation was therefore mediated by ELP2. These results suggest that ELP2 is upregulated at the pyroptosis of MC3T3-E1 cells and inhibits osteogenic differentiation in response to TNF-α through NLRP3-GSDMD/GSDME activation.

Effects of mitochondrial dysfunction on bone metabolism and related diseases: a scientometric study from 2003 to 2022.

BACKGROUND: In recent years, mitochondrial dysfunction has been extensively studied and published, but research on the effects of mitochondrial dysfunction on bone metabolism and related diseases is only just beginning. Furthermore, no studies have been carried out to systematically illustrate this area from a scientometric point of view. The goal of this research is to review existing knowledge and identify new trends and possible hotspots in this area. METHODS: All publications related to the relationship between mitochondrial dysfunction and bone metabolism and related diseases from 2003 to 2022 were searched at the Web of Science Core Collection (WoSCC) on May 7, 2022. Four different analytical tools: VOSviewer 1.6.18, CiteSpace V 6.1, HistorCite (12.03.07), and Excel 2021 were used for the scientometric research. RESULTS: The final analysis included 555 valid records in total. Journal of Biological Chemistry (Co-citations = 916) is the most famous journal in this field. China (Percentage = 37%), the United States (Percentage = 24%), and Korea (Percentage = 12%) are the most productive countries. Blanco FJ and Choi EM are the main researchers with significant academic influence. Current research hotspots are basic research on mitochondrial dysfunction and the prevention or treatment of bone metabolism-related diseases. CONCLUSION: The study of the consequences of mitochondrial dysfunction on bone metabolism and associated diseases is advancing rapidly. Several prominent researchers have published extensive literature and are widely cited. Future research in this area will focus on oxidative stress, aging, gene expression, and the pathogenesis of bone metabolism-related diseases.

ELP2 negatively regulates osteoblastic differentiation impaired by tumor necrosis factor α in MC3T3-E1 cells through STAT3 activation.

Tumor necrosis factor-α (TNF-α) is a pluripotent signaling molecule. The biological effect of TNF-α includes slowing down osteogenic differentiation, which can lead to bone dysplasia in long-term inflammatory microenvironments. Signal transducer and activator of transcription 3 (STAT3)-interacting protein 1 (StIP1, also known as elongator complex protein 2, ELP2) play a role in inhibiting TNF-α-induced osteoblast differentiation. In the present study, we investigated whether and how ELP2 activation mediates the effects of TNF-α on osteoblastic differentiation. Using in vitro cell cultures of preosteoblastic MC3T3-E1 cells, we found that TNF-α inhibited osteoblastic differentiation accompanied by an increase in ELP2 expression and STAT3 activation. Forced ELP2 expression inhibited osteogenic differentiation of MC3T3-E1 cells, with a decrease in the expression of osteoblast marker genes, alkaline phosphatase activity, and matrix mineralization capacity. In contrast, ELP2 silencing ameliorated osteogenic differentiation in MC3T3-E1 cells, even after TNF-α stimulation. The TNF-α-induced inhibitory effect on osteoblastic differentiation was therefore mediated by ELP2, which was associated with Janus kinase 2 (JAK2)/STAT3 activation. These results suggest that ELP2 is upregulated at the differentiation of MC3T3-E1 cells into osteoblasts and inhibits osteogenic differentiation in response to TNF-α through STAT3 activation.

Are platelet concentrates an ideal biomaterial for arthroscopic rotator cuff repair? A meta-analysis of randomized controlled trials.

PURPOSE: The present study aims to conduct a meta-analysis of Level I evidence studies to investigate the efficacy of concomitant platelet concentrate (PC) used in arthroscopic rotator cuff repair. METHODS: We systematically searched electronic databases to identify randomized controlled trials (RCTs) evaluating the role of PC augmentation in arthroscopic rotator cuff repairs for patients with full-thickness tears. The search strategy followed the requirements in the Cochrane Library Handbook. The primary outcome was retearing of the rotator cuff. Functional outcomes were analyzed in terms of Constant score, specific Constant pain score, University of California, Los Angeles (UCLA) shoulder score, Simple Shoulder Test (SST) score, and American Shoulder and Elbow Surgeons (ASES) score. RESULTS: Seven studies with a total of 417 patients available at the latest follow-up reporting data about retears were analyzed in this meta-analysis. However, 4 studies with Constant scores (n = 237), 3 studies with UCLA scores (n = 168), 2 studies with Constant pain scores (n = 164), 2 studies with ASES scores (n = 101), and 2 studies with SST scores (n = 121) were analyzed. The retear rates and functional scores showed that there was no significant efficacy of PC application in arthroscopic rotator cuff repairs. CONCLUSIONS: This meta-analysis of high-level evidence suggests that PCs have no benefit regarding retear rate and overall clinical outcomes for the arthroscopic repair of full-thickness rotator cuff tears. LEVEL OF EVIDENCE: Level II, meta-analysis of randomized controlled trials.

Unilateral versus bilateral fixation for lumbar spinal fusion: a systemic review and meta-analysis.

PURPOSE: The objective of this study was to systematically compare the efficacy and safety of unilateral fixation to bilateral fixation for the lumbar degenerative disease. STUDY DESIGN: Systematic review and meta-analysis. METHODS: We searched databases including PubMed Central, MEDLINE (from 1966), EMBASE (from 1980), and Cochrane Central Register of Controlled Trials databases for randomized controlled trials or non-randomized controlled trials that compare unilateral fixation with bilateral fixation for the treatment for lumbar disease. Exclusion criteria were non-controlled studies, follow-up <6 months, combined anterior and posterior surgery, lumbar tumors, and non-English writing paper. Methodologic quality was assessed, relevant data were retrieved, and the appropriate meta-analysis was performed. Two review authors independently selected studies, extracted data, and assessed the risk of bias. The main end points included the rate of fusion, visual analogue scale (VAS), Oswestry disability index (ODI), intra-operative blood loss, operating time, and the rate of complications. RESULTS: A total of seven studies were included in the meta-analysis. Four relevant randomized controlled trials, one prospective study, and two retrospective studies involving 499 patients were identified. Patients in unilateral pedicle fixation group compared with bilateral pedicle screw fixation group on the fusion rate, VAS, ODI scores, and complication rate demonstrated no significant differences (P > 0.05, respectively). However, intra-operative blood loss and operating time in unilateral fixation group were significantly less than bilateral fixation group (P < 0.0001, respectively). CONCLUSIONS: Unilateral fixation seems to be an effective, feasible, and safe procedure in one or two segmental disease when compare with bilateral instrumentation.

A novel approach for diabetic foot diagnosis: Deep learning-based detection of lower extremity arterial stenosis.

PURPOSE OF THE STUDY: Assessing the lower extremity arterial stenosis scores (LEASS) in patients with diabetic foot ulcer (DFU) is a challenging task that requires considerable time and efforts from physicians, and it may yield varying results. The presence of vascular wall calcification and other irrelevant tissue information surrounding the vessel can further compound the difficulties of this evaluation. Automatic detection of lower extremity arterial stenosis (LEAS) is expected to help doctors develop treatment plans for patients faster. METHODS: In this paper, we first reconstructed the 3D model of blood vessels by medical digital image processing and then utilized it as the training data for deep learning (DL) in conjunction with the non-calcified part of blood vessels in the original data. We proposed an improved model of vascular stenosis small target detection based on YOLOv5. We added Convolutional Block Attention Module (CBAM) in backbone, replaced Path Aggregation Network (PANET) with Bidirectional Feature Pyramid Network (BiFPN) and replaced C3 with GhostC3 in neck to improve the recognition of three types of stenosis targets (I: <50 %, II: 51 % - 99 %, III: completely occluded). Additionally, we utilized K-Means++ instead of K-Means for better algorithm convergence performance, and enhanced the Complete-IoU (CIoU) loss function to Alpha-Scylla-IoU (ASIoU) loss for faster reasoning and convergence. Lastly, we conducted comparisons between our approach and five other prominent models. RESULT: Our method had the best average ability to detect three types of stenosis with 85.40% mean Average Precision (mAP) and 74.60 Frames Per Second (FPS) and explored the possibility of applying DL to the detection of LEAS in diabetic foot. The code is available at github.com/wuchongxin/yolov5_LEAS.git.

MicroRNA-18a regulates the Pyroptosis, Apoptosis, and Necroptosis (PANoptosis) of osteoblasts induced by tumor necrosis factor-α via hypoxia-inducible factor-1α.

BACKGROUND: Tumor necrosis factor-α (TNF-α) is involved in inflammatory responses and promotes cell death and the inhibition of osteogenic differentiation. MicroRNA (miRNA) plays a crucial role in the infected bone diseases, however, the biological role of miRNAs in inflammation-induced impaired osteogenic differentiation remains unclear. This study aimed to explore the role of miRNA-18a-5p (miR-18a) in regulating PANoptosis and osteogenic differentiation in an inflammatory environment via hypoxia-inducible factor-1α (HIF1-α). METHODS: The expression of miR-18a in MC3T3-E1 cells was analyzed using quantitative reverse transcription-polymerase chain reaction in an inflammatory environment induced by TNF-α. The expression of HIF1-α and NLRP3 in LV-miR-18a or sh-miR-18a cells was analyzed using western blotting. Fluorescence imaging for cell death, flow cytometry, and alkaline phosphatase activity analysis were used to analyze the role of miR-18a in TNF-α-induced PANoptosis and the inhibition of osteogenic differentiation. An animal model of infectious bone defect was established to validate the regulatory role of miR-18a in an inflammatory environment. RESULTS: The expression of miRNA-18a in the MC3T3-E1 cell line was significantly lower under TNF-α stimulation than in the normal environment. miR-18a significantly inhibited the expression of HIF1-α and NLRP3, and inhibition of HIF1-α expression further inhibited NLRP3 expression. Furthermore, inhibition of miR-18a expression promoted the TNF-α-induced PANoptosis and inhibition of osteogenic differentiation, whereas miR-18a overexpression and the inhibition of both HIF1-α and NLRP3 reduced the effects of TNF-α. These findings are consistent with those of the animal experiments. CONCLUSION: miRNA-18a negatively affects HIF1-α/NLRP3 expression, inhibits inflammation-induced PANoptosis, and impairs osteogenic differentiation. Thus, it is a potential therapeutic candidate for developing anti-inflammatory strategies for infected bone diseases.

Chronic osteomyelitis risk is associated with NLRP3 gene rs10754558 polymorphism in a Chinese Han Population.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the nucleotide-binding domain leucine-rich repeat protein-3 (NLRP3) gene are reported to be linked to many inflammatory disorders. However, uncertainty persists over the associations between these SNPs and susceptibilities to chronic osteomyelitis (COM). This study aimed to investigate potential relationships between NLRP3 gene SNPs and the risks of developing COM in a Chinese Han cohort. METHODS: The four tag SNPs of the NLRP3 gene were genotyped in a total of 428 COM patients and 368 healthy controlsusing the SNapShot technique. The genotype distribution, mutant allele frequency, and the four genetic models (dominant, recessive, homozygous, and heterozygous) of the four SNPs were compared between the two groups. RESULTS: A significant association was found between rs10754558 polymorphism and the probability of COM occurence by the heterozygous model (P = 0.037, odds ratio [OR] = 1.541, 95% confidence interval [CI] = 1.025-2.319), indicating that rs10754558 may be associated with a higher risk of developing COM.In addition, possible relationship was found between rs7525979 polymorphism and the risk of COM development by the outcomes of homozygous (P = 0.073, OR = 0.453, 95% CI = 0.187-1.097) and recessive (P = 0.093, OR = 0.478, 95% CI = 0.198-1.151) models, though no statistical differences were obtained. CONCLUSIONS: Outcomes of the present study showed, for the first time, that rs10754558 polymorphism of the NLRP3 gene may increase the risk of COM development in this Chinese Han population, with genotype CG as a risk factor. Nonetheless, this conclusion requires verification from further studies with a larger sample size.

Global trends in publications regarding macrophages-related diabetic foot ulcers in the last two decades.

BACKGROUND: Diabetic foot ulcers (DFUs) are one of the most severe and popular complications of diabetes. The persistent non-healing of DFUs is the leading cause of ampu-tation, which causes significant mental and financial stress to patients and their families. Macrophages are critical cells in wound healing and perform essential roles in all phases of wound healing. However, no studies have been carried out to systematically illustrate this area from a scientometric point of view. Although there have been some bibliometric studies on diabetes, reports focusing on the investigation of macrophages in DFUs are lacking. AIM: To perform a bibliometric analysis to systematically assess the current state of research on macrophage-related DFUs. METHODS: The publications of macrophage-related DFUs from January 1, 2004, to December 31, 2023, were retrieved from the Web of Science Core Collection on January 9, 2024. Four different analytical tools: VOSviewer (v1.6.19), CiteSpace (v6.2.R4), HistCite (v12.03.07), and Excel 2021 were used for the scientometric research. RESULTS: A total of 330 articles on macrophage-related DFUs were retrieved. The most published countries, institutions, journals, and authors in this field were China, Shanghai Jiao Tong University of China, Wound Repair and Regeneration, and Aristidis Veves. Through the analysis of keyword co-occurrence networks, historical direct citation networks, thematic maps, and trend topics maps, we synthesized the prevailing research hotspots and emerging trends in this field. CONCLUSION: Our bibliometric analysis provides a comprehensive overview of macrophage-related DFUs research and insights into promising upcoming research.

Microbiological profile of diabetic foot infections in China and worldwide: a 20-year systematic review.

Introduction: Pathogens causing diabetic foot infections (DFIs) vary by region globally; however, knowledge of the causative organism is essential for effective empirical treatment. We aimed to determine the incidence and antibiotic susceptibility of DFI pathogens worldwide, focusing on Asia and China. Methods: Through a comprehensive literature search, we identified published studies on organisms isolated from DFI wounds from January 2000 to December 2020. Results: Based on our inclusion criteria, we analyzed 245 studies that cumulatively reported 38,744 patients and 41,427 isolated microorganisms. DFI pathogens varied according to time and region. Over time, the incidence of Gram-positive and Gram-negative aerobic bacteria have decreased and increased, respectively. America and Asia have the highest (62.74%) and lowest (44.82%) incidence of Gram-negative bacteria, respectively. Africa has the highest incidence (26.90%) of methicillin-resistant Staphylococcus aureus. Asia has the highest incidence (49.36%) of Gram-negative aerobic bacteria with species infection rates as follows: Escherichia coli, 10.77%; Enterobacter spp., 3.95%; and Pseudomonas aeruginosa, 11.08%, with higher local rates in China and Southeast Asia. Linezolid, vancomycin, and teicoplanin were the most active agents against Gram-positive aerobes, while imipenem and cefoperazone-sulbactam were the most active agents against Gram-negative aerobes. Discussion: This systematic review showed that over 20 years, the pathogens causing DFIs varied considerably over time and region. This data may inform local clinical guidelines on empirical antibiotic therapy for DFI in China and globally. Regular large-scale epidemiological studies are necessary to identify trends in DFI pathogenic bacteria. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447645.

Single-bundle versus double-bundle anterior cruciate ligament reconstruction: an up-to-date meta-analysis.

PURPOSE: The aim of this meta-analysis was to compare the results of arthroscopic single-bundle and double-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: We systematically searched electronic databases to identify randomised controlled trials (RCTs) in which arthroscopic single-bundle was compared with double-bundle for ACL reconstruction. The search strategy followed the requirements of the Cochrane Library Handbook. The outcomes of these studies were analysed in terms of graft failures, Lysholm score, negative pivot-shift test, KT1000 arthrometer measurements, knee extensor and flexor peak torques, knee extension and flexion deficit, and subjective and objective International Knee Documentation Committee (IKDC) final score. Methodological quality was assessed and data were extracted independently. Standard mean difference (SMD) or odds ratio (OR) with 95 % confidence interval (CI) was calculated by a fixed effects or random effects model. Heterogeneity across the studies was assessed with the I-square and chi-square statistic. Forest plots were also generated. RESULTS: We identified 17 RCTs comprising 1,381 patients who were treated by arthroscopic single-bundle versus double-bundle ACL reconstruction. The results of meta-analysis of these studies showed that arthroscopic double-bundle reconstruction was associated with a lower risk of graft failures (P=0.002) and a lower rate of positive pivot-shift test (P<0.0001). Compared with single-bundle reconstruction, double-bundle reconstruction had a lower KT1000 arthrometer measurement (P<0.00001), a lower knee extension deficit (P=0.006) and a higher subjective IKDC score (P=0.03). There was no statistically significant difference between single-bundle and double-bundle reconstruction in Lysholm score (P=0.91), knee extensor peak torques (P=0.97), knee flexor peak torques (P=0.96), knee flexion deficit (P=0.30) and objective IKDC score (P=0.18). CONCLUSIONS: Considering the more favourable outcomes of graft failures, knee joint stability and knee joint function in double-bundle reconstruction, we concluded that arthroscopic double-bundle reconstruction should be considered as the primary treatment in ACL reconstruction.

Should displaced midshaft clavicular fractures be treated surgically? A meta-analysis based on current evidence.

PURPOSE: This study was designed to compare clinical effectiveness of operative with nonoperative treatment for displaced midshaft clavicular fractures (DMCF). METHODS: We systematically searched electronic databases (MEDILINE, EMBASE, CLINICAL, OVID, BIOSIS and Cochrane registry of controlled clinical trials) to identify randomized controlled trials (RCTs) in which operative treatment was compared with nonoperative treatment for DMCF from 1980 to 2012. The methodologic quality of trials was assessed. Data from chosen studies were pooled with using of fixed-effects and random-effects models with mean differences and risk ratios for continuous and dichotomous variables, respectively. RESULTS: Four RCTs with a total of 321 patients were screened for the present study. Results showed that the operative treatment was superior to the nonoperative treatment regarding the rate of nonunion [95 % confidence interval (CI) (0.05, 0.43), P = 0.0004], malunion [95 % CI (0.06, 0.34), P < 0.00001] and overall complication [95 % CI (0.43-0.76), P = 0.0001]. Subgroup analyses of complications revealed that significant differences were existed in the incidence of neurologic symptoms [95 % CI (0.20, 0.74), P = 0.004] and dissatisfaction with appearance [95 % CI (0.19, 0.65), P = 0.001]. Lack of consistent and standardized assessment data, insufficiency analysis that carried out showed improved functional outcomes (P < 0.05) in operative treatment. CONCLUSIONS: The available evidence suggests that the operative treatment for DMCF is associated with a lower rate of nonunion, malunion and complication than nonoperative treatment. This study supports traditional primary operative treatment for DMCF in active adults.

Induced membrane technique in the treatment of infected tibial bone defect: A retrospective study.

To investigate the effect of the induced membrane technique (IMT) in the treatment of infected tibial bone defect. IMT is a 2-stage procedure dedicated to reconstruction of bone defects of the limbs. Treating injuries of the tibia characterized by segmental bone loss, severe damage to the soft tissue, and a conjoining infection is a challenge using IMT. A retrospective study was performed among the patients treated using IMT for infected tibial bone defect between 2017 and 2020. The complications were recorded, and the bone defect union and the functional results were evaluated by Paley method. All patients were followed up for at least 1 year. We included 12 patients (11 males) with a mean age of 44.5 years (range 19-65). The mean length of bone defect was 26.7 mm (range 10-60). The mean interval between the stage 1 and the stage 2 of the procedure was 11.8 weeks (range 4-32). At a mean follow-up of 18.08 months (range 12-32), bone union was achieved in all cases in a mean time of 8 months (range 5-16) without infection recurrence, where 1 patient received additional bone grafting. The joint function recovered well for the patients and the rate of functionally excellent and good results was 9/12. IMT in the treatment of infected tibial bone defect offers the advantages of simple operation, use of a smaller amount of autograft bone, and low recurrence rate of infection.

Photothermal effective CeO2NPs combined in thermosensitive hydrogels with enhanced antibacterial, antioxidant and vascularization performance to accelerate infected diabetic wound healing.

Chronic diabetic wound healing remains a formidable challenge due to susceptibility to bacterial infection, excessive oxidative stress, and poor angiogenesis. To address these issues, a sodium alginate (SA) based photothermal hydrogel dressing with multifunction was fabricated to facilitate wound treatment. Ceria nanoparticles (CeO2NPs) was synthesized, and their antibacterial performance by near-infrared light triggered photothermal effects was first studied and verified in this work. In addition, to release CeO2NPs to achieve antioxidation and pro-vascularization, thermosensitive gelatin (Gel) was utilized to embed the nanoparticles in advance and then composited in SA hydrogel networks. SA network was finally strengthened by acid soaking to form partially crystalline regions to act as natural crosslinkers. Results showed that the Gel/SA/CeO2 hydrogel displayed temperature-responsive release of CeO2NPs, significant antibacterial and antioxidative activity, as well as the ability to remove without injury and promote infected diabetic wound healing with low cytotoxicity, according to antibacterial investigations, cell studies, and in vivo animal studies. This research offers not only a successful method for quickening the healing of diabetic wounds but also a fresh approach to the general use of CeO2NPs.

Tibial cortex transverse transport potentiates diabetic wound healing via activation of SDF-1/CXCR4 signaling.

Background: The current treatments for diabetic foot ulcers have disadvantages of slow action and numerous complications. Tibial cortex transverse transport (TTT) surgery is an extension of the Ilizarov technique used to treat diabetic foot ulcers, and can shorten the repair time of diabetic foot ulcers. This study assessed the TTT technique for its effectiveness in healing diabetic foot ulcer skin lesions and its related molecular mechanisms. Methods: Diabetic rat models were established by injecting healthy Sprague-Dawley rats with streptozotocin (STZ). The effects of TTT surgery on the model rats were assessed by recording changes in body weight, analyzing skin wound pictures, and performing H&E staining to assess the recovery of wounded skin. The numbers of endothelial progenitor cells (EPCs) in peripheral blood were analyzed by flow cytometry, and levels of CXCR4 and SDF-1 expression were qualitatively analyzed by immunofluorescence, immunohistochemistry, qRT-PCR, and western blotting. Results: Both the histological results and foot wound pictures indicated that TTT promoted diabetic wound healing. Flow cytometry results showed that TTT increased the numbers of EPCs in peripheral blood as determined by CD34 and CD133 expression. In addition, activation of the SDF-1/CXCR4 signaling pathway and an accumulation of EPCs were observed in skin ulcers sites after TTT surgery. Finally, the levels of SDF-1 and CXCR4 mRNA and protein expression in the TTT group were higher than those in a blank or fixator group. Conclusion: TTT promoted skin wound healing in diabetic foot ulcers possibly by activating the SDF-1/CXCR4 signaling pathway.

Posttraumatic Osteomyelitis Risks Associated with NLRP3 Gene Polymorphisms in the Chinese Population.

The purpose of this case-control study was to examine possible links between NLRP3 gene polymorphisms and the risk of developing posttraumatic osteomyelitis (PTOM) in the Chinese population. A total of 306 patients with PTOM and 368 normal controls were genotyped for NLRP3 (rs35829419, rs10754558, rs7525979, rs4612666), ELP2 (rs1785929, rs1789547, rs1785928, rs12185396, rs681757, rs8299, rs2032206, rs559289), STAT3 (rs4796793, rs744166, rs1026916, rs2293152, rs1053004), CASP1 (rs501192, rs580253, rs556205, rs530537), NFKBIA (rs696), NFKB1 (rs4648068), CARD8 (rs204321), and CD14 (rs2569190) using the genotyping technique SNaPshot. The genotype distributions of NLRP3 gene rs10754558 (p = 0.047) and rs7525979 (p = 0.048) significantly differed between the patients and the healthy controls. Additionally, heterozygous models indicated a significant association between NLRP3 rs10754558 and the likelihood of developing PTOM (OR = 1.600, p = 0.039), as did recessive and homozygous models of NLRP3 rs7525979 (OR = 0.248, p = 0.019 and 0.239, p = 0.016, respectively). Collectively, our findings suggest that, in the Chinese population, the risk of developing PTOM was increased by the association between NLRP3 rs10754558 and rs7525979. Therefore, our findings may provide novel insights and guidance in the prevention and development of PTOM.

Antibacterial Cellulose Nanocrystal-Incorporated Hydrogels With Satisfactory Vascularization for Enhancing Skin Regeneration.

Wound healing of skin defects remains a significant clinical problem due to inflammation, infection, and dysangiogenesis; especially, the promotion of microvasculature formation in healing of chronic wound or deep skin defects is critical as it supplies oxygen and nutrients to the impaired tissue, relieving uncontrolled inflammatory responses. The cellulose nanocrystals (CNCs) in the liquid crystalline phase, which facilitates cell proliferation and migration, has been shown to improve vascularization effectively. Therefore, we developed a novel injectable hydrogel based on Schiff base and coordination of catechol and Ag. The obtained hydrogels (CCS/CCHO-Ag) exhibited in situ forming properties, satisfactory mechanical performance, controlled release of Ag, antibacterial capacity, and biocompatibility. In addition, the hydrogels could also entirely cover and firmly attach wounds with irregular shapes, so as to reduce the re-injury rate. More importantly, experiments in vitro and in vivo demonstrated that CCS/CCHO-Ag hydrogels can promote neovascularization and tissue regeneration, thanks to their anti-inflammatory and antibacterial effects. In conclusion, these multifunctional hydrogels are well on the way to becoming competitive biomedical dressings, which show tremendous potential application in the field of tissue engineering.