There is an urgent clinical need for an appropriate method to shorten skin healing time. Among most factors related to wound healing, M2 macrophages will be recruited to the wound area and play a pivotal role in a time-limiting factor, angiogenesis. The exploration of exosomes derived from M2 in angiogenesis promotion is an attractive research field. In this project, we found that exosomes from M2 (M2-EXO) promoted the angiogenic ability of HUVECs in vitro. With a series of characteristic experiments, we demonstrated that M2-EXO inhibited PTEN expression in HUVECs by transferring miR-21, and further activated AKT/mTOR pathway. Then, using a full-thickness cutaneous wound mice model, we demonstrated that M2-EXO could be used as a promotor of angiogenesis and regeneration in vivo. Furthermore, M2-EXO-treated skin wounds exhibited regeneration of functional microstructures. These results demonstrate that M2-EXO can be used as a promising nanomedicine strategy for therapeutic exploration of skin healing with the potential to be translated into clinical practice.

Preoperative diagnosis is important for patients who need revision surgery due to PJI. Microbial culture plays an important role in PJI diagnosis, but the sensitivity of cultures is low when the sample amount is limited or when a patient is treated with antibiotics before sample collection. In this study, metagenomic next-generation sequencing (mNGS) was used to detect bacteria in preoperative puncture synovial fluid samples from patients with suspected PJI, and the preoperative and intraoperative culture results were compared to estimate the diagnostic efficiency. From July 2016 to December 2018, patients with suspected PJI who underwent prosthetic joint revision surgery were included, and the results of those who had been tested by preoperative synovial fluid culture and mNGS were obtained. The demographic characteristics, medical history, laboratory test results, culture results, and mNGS results of each patient were recorded. Then, the efficiency of preoperative synovial fluid mNGS was compared to that of synovial fluid culture for diagnosing PJI. A total of 37 patients were included, and 24 patients (25 joints) were diagnosed with PJI. The sensitivity, specificity and accuracy of preoperative synovial fluid mNGS were 92%, 91.7%, and 83.7%, respectively. The sensitivity, specificity and accuracy of preoperative synovial fluid culture were 52%, 91.7% and 43.7%, respectively. With a low volume of synovia (1 ml) mNGS can be performed with a higher sensitivity and specificity as compared to synovial culture. Thus, mNGS can be used as an effective supplemental method to improve diagnostic efficiency during the preoperative period.

Aims: Metagenomic next-generation sequencing (mNGS) is useful in the diagnosis of infectious disease. However, while it is highly sensitive at identifying bacteria, it does not provide information on the sensitivity of the organisms to antibiotics. The purpose of this study was to determine whether the results of mNGS can be used to guide optimization of culture methods to improve the sensitivity of culture from intraoperative samples. Methods: Between July 2014 and October 2019, patients with suspected joint infection (JI) from whom synovial fluid (SF) was obtained preoperatively were enrolled. Preoperative aspirated SF was analyzed by conventional microbial culture and mNGS. In addition to samples taken for conventional microbial culture, some samples were taken for intraoperative culture to optimize the culture method according to the preoperative mNGS results. The demographic characteristics, medical history, laboratory examination, mNGS, and culture results of the patients were recorded, and the possibility of the optimized culture methods improving diagnostic efficiency was evaluated. Results: A total of 56 cases were included in this study. There were 35 cases of JI and 21 cases of non-joint infection (NJI). The sensitivity, specificity, and accuracy of intraoperative microbial culture after optimization of the culture method were 94.29%, 76.19%, and 87.5%, respectively, while those of the conventional microbial culture method were 60%, 80.95%, and 67.86%, respectively. Conclusion: Preoperative aspirated SF detected via mNGS can provide more aetiological information than preoperative culture, which can guide the optimization and improve the sensitivity of intraoperative culture. Cite this article: Bone Joint J 2021;103-B(1):39–45.

Aims: This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) . Methods: A total of 63 patients who were suspected of PJI were enrolled. The synovial fluid calprotectin was tested by an enzyme-linked immunosorbent assay (ELISA). Laboratory test data, such as ESR, CRP, synovial fluid white blood cells (SF-WBCs), and synovial fluid polymorphonuclear cells (SF-PMNs), were documented. Chi-squared tests were used to compare the sensitivity and specificity of calprotectin and laboratory tests. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to determine diagnostic efficacy. Results: The median calprotectin level was 776 μg/ml (interquartile range (IQR) 536.5 to 1132) in the PJI group and 54.5 μg/ml (IQR, 38.75 to 78.25) in the aseptic failure (AF) group (p < 0.05). Using a threshold of 173 ug/ml, the sensitivity was 95.2%, with a 97.6% specificity, and the AUC was 0.993. The sensitivity of calprotectin of the antibiotic-treated PJI group was 100% versus 90.9% of the non-antibiotic-treated PJI group. Although 47.6% (ten cases) of the patients in the PJI group received antibiotics before aspiration, the diagnostic efficacy of calprotectin was not affected. The sensitivity and specificity of ESR, CRP, SF-WBCs, and SF-PMNs ranged from 76.2% to 90.5% and 64.3% to 85.7%, respectively. Conclusion: Calprotectin in synovial fluid has great diagnostic efficacy for PJI diagnosisand outperformed ESR, CRP, SF-WBCs, and SF-PMNs. Cite this article: Bone Joint Res 2020;9(8):450–456.

Background: The relationship between osteoarthritis (OA) and senile central nervous system dysfunctions (CNSDs), including Parkinson’s disease (PD), Alzheimer’s disease (AD), and ischemic stroke (IS) has gradually attracted attention. At present, the causal relationship between OA and CNSD remains unclear. The aim of this study was to assess the causal effects of CNSD and OA using Mendelian randomization (MR).Methods: Genome-wide association study summary data for CNSD and OA were obtained. Single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs), and significant (P < 5.0 × 10^–8) and independent (r² < 0.1) SNPs were extracted for bidirectional MR analysis. Inverse variance weighted (IVW) was used to assess these causal relationships. The results are reported as odds ratios (ORs). Subsequently, heterogeneity was tested using the Cochran’s Q test, pleiotropy was tested using the MR-Egger intercept, and sensitivity analysis was performed using the leave-one-out sensitivity test.Results: The MR results of the causal relationship between PD and OA showed that there was a positive causal effect of OA on PD, which was estimated by IVW (OR = 1.194, 95%CI = 1.036, 1.378; P = 0.0144). Moreover, the MR analysis by IVW also showed that IS had a positive effect on OA (OR = 1.033, 95%CI = 1.002, 1.066; P = 0.0355). These results are reliable and stable, as confirmed by sensitivity tests.Conclusion: This study showed a positive causal effect of OA on PD, but there was a null effect of OA on AD and OA on IS.

Aims: Microbiological culture is a key element in the diagnosis of periprosthetic joint infection (PJI). However, cultures of periprosthetic tissue do not have optimal sensitivity. One of the main reasons for this is that microorganisms are not released from the tissues, either due to biofilm formation or intracellular persistence. This study aimed to optimize tissue pretreatment methods in order to improve detection of microorganisms. Methods: From December 2017 to September 2019, patients undergoing revision arthroplasty in a single centre due to PJI and aseptic failure (AF) were included, with demographic data and laboratory test results recorded prospectively. Periprosthetic tissue samples were collected intraoperatively and assigned to tissue-mechanical homogenization (T-MH), tissue-manual milling (T-MM), tissue-dithiothreitol (T-DTT) treatment, tissue-sonication (T-S), and tissue-direct culture (T-D). The yield of the microbial cultures was then analyzed. Results: A total of 46 patients were enrolled, including 28 patients in the PJI group and 18 patients in the AF group. In the PJI group, 23 cases had positive culture results via T-MH, 22 cases via T-DTT, 20 cases via T-S, 15 cases via T-MM, and 13 cases via T-D. Three cases under ongoing antibiotic treatment remained culture-negative. Five tissue samples provided the optimal yield. Any ongoing antibiotic treatment had a relevant influence on culture sensitivity, except for T-DTT. Conclusion: T-MH had the highest sensitivity. Combining T-MH with T-DTT, which requires no special equipment, may effectively improve bacterial detection in PJI. A total of five periprosthetic tissue biopsies should be sampled in revision arthroplasty for optimal detection of PJI. Cite this article: Bone Joint Res 2021;10(2):96–104.