Aim: To provide a systematic analysis of the study design in knee osteoarthritis (OA) preclinical studies, focusing on the characteristics of animal models and cell doses, and to compare these to the characteristics of clinical trials using mesenchymal stem cells (MSCs) for the treatment of knee OA.Method: A systematic and comprehensive search was conducted using the PubMed, Web of Science, Ovid, and Embase electronic databases for research papers published in 2009-2020 on testing MSC treatment in OA animal models. The PubMed database and ClinicalTrials.gov website were used to search for published studies reporting clinical trials of MSC therapy for knee OA. Results:In total, 9234 articles and two additional records were retrieved, of which 120 studies comprising preclinical and clinical studies were included for analysis. Among the preclinical studies, rats were the most commonly used species for modeling knee OA, and anterior cruciate ligament transection was the most commonly used method for inducing OA. There was a correlation between the cell dose and body weight of the animal. In clinical trials, there was large variation in the dose of MSCs used to treat knee OA, ranging from 1 × 10 6 to 200 × 10 6 cells with an average of 37.91 × 10 6 cells. Conclusion: Mesenchymal stem cells have shown great potential in improving pain relief and tissue protection in both preclinical and clinical studies of knee OA. Further high-quality preclinical and clinical studies are needed to explore the dose | 533 WANG et Al. Study Animal species Sample size OA modeling method Cell type Cell donor

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Purpose Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation. Methods The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice. Results The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis. Conclusion These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation.

ObjectiveTo identify whether the medial or lateral approach is superior for patients with valgus knees undergoing primary total knee arthroplasty (TKA).MethodsStudies evaluating the 2 approaches were sourced from the PUBMED, EMBASE, Web of Science, and OVID databases. The quality of included studies was assessed using a modified quality evaluation method, and differences between approaches were systematically reviewed.ResultsSeventeen observational studies were included. The studies were published between 1991 and 2016, and included 5 retrospective studies and 12 prospective studies. Sixteen evaluation methods for the study outcomes were identified. Twelve and eight complication types were identified by studies reporting the lateral and medial approaches for valgus knee, respectively. Several studies showed that pain scores and knee function were superior using a lateral approach.ConclusionThe lateral approach (combined with a tibial tubercle osteotomy or proximal quadriceps snip) was more useful and safer than the medial approach in the treatment of severe uncorrectable valgus knee deformity in patients undergoing TKA. Most of the available evidence supports the use of a lateral approach provided that the surgeon is familiar with the pathological anatomy of the valgus knee.

Purpose Anterior cruciate ligament (ACL) reconstruction is widely accepted as the first choice of treatment for ACL injury, but there is disagreement in the literature regarding the optimal femoral fixation method. This meta-analysis assesses the evidence surrounding three common femoral fixation methods: cortical button (CB), cross-pin (CP) and interference screws (IS). Methods A systematic search was conducted in Medline, EMBASE and the Cochrane Library to identify studies with evidence level I or II that compared at least two femoral fixation methods with hamstring autograft for ACL reconstruction. Ten primary outcomes were collected. Risk of bias was assessed following the Cochrane Handbook for Systematic Reviews of Interventions. Standardized mean differences (SMD) were estimated using random-effects network meta-analysis in a Bayesian framework. Probability of ranking best (ProBest) and surface under the cumulative ranking curve (SUCRA) were used to rank all treatments. Funnel plots were used to identify publication bias and small-study effects. Results Sixteen clinical trials were included for analysis out of 2536 retrieved studies. Bayesian network meta-analysis showed no significant differences among the three fixation methods for the ten primary outcome measures. Based on the 10 outcome measures, the IS, CB and CP had the highest ProBest in 5, 5 and 0 outcomes, and the highest SUCRA values in 5, 4 and 1 outcomes, respectively. No substantial inconsistency between direct and indirect evidence, or publication bias was detected in the outcomes. Conclusion There were no statistical differences in performance among the CP, CB and IS femoral fixation methods with hamstring autograft in ACL reconstruction, although the IS was more likely to perform better than CB and CP based on the analysis of outcome measures from the included studies. Level of evidence 1.