Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts individuals and healthcare systems worldwide. However, the exploration of N6-methyladenosine (m6A)-related aging genes in OA pathogenesis remains largely underexplored. This study aimed to elucidate the role of m6A-related aging genes in OA and to develop a robust diagnostic model based on their expression profiles. Leveraging publicly available gene expression datasets, we conducted consensus clustering to categorize OA into distinct subtypes, guided by the expression patterns of m6A-related aging genes. Utilizing XGBoost, a cutting-edge machine learning approach, we identified key diagnostic genes and constructed a predictive model. Our investigation extended to the immune functions of these genes, shedding light on potential therapeutic targets and underlying regulatory mechanisms. Our analysis unveiled specific OA subtypes, each marked by unique expression profiles of m6A-related aging genes. We pinpointed a set of pivotal diagnostic genes, offering potential therapeutic avenues. The developed diagnostic model exhibited exceptional capability in distinguishing OA patients from healthy controls. To corroborate our computational findings, we performed quantitative real-time polymerase chain reaction analyses on two cell lines: HC-OA (representing adult osteoarthritis cells) and C-28/I2 (representative of normal human chondrocytes). The gene expression patterns observed were consistent with our bioinformatics predictions, further validating our initial results. In conclusion, this study underscores the significance of m6A-related aging genes as promising biomarkers for diagnosis and prognosis, as well as potential therapeutic targets in OA. Although these findings are encouraging, further validation and functional analyses are crucial for their clinical application.

Objective Weight is an influential factor in knee osteoarthritis (KOA). However, the effect of abnormal body weight on chitosan's efficacy in treating KOA is unclear. This study aimed to explore the differences in the effectiveness of arthroscopic surgery combined with intra‐articular chitosan injection for KOA in patients with abnormal body weight. Methods Patients with stage II‐III KOA (Kellgren–Lawrence rating, K‐L) undergoing arthroscopic surgery were recruited for this clinical study from January 2020 to September 2021. Based on body mass index (BMI) and intra‐articular chitosan injection, patients with KOA undergoing arthroscopic surgery (138 patients) were divided into four groups: low‐weight‐non‐injection (Lw‐N, BMI <18.5); low‐weight‐chitosan injection (Lw‐CS, BMI <18.5); overweight‐non‐injection (Ow‐N, BMI ≥25); overweight‐chitosan injection (Ow‐CS, BMI ≥25). A 2‐year follow‐up was conducted to evaluate various indicators, including the visual analogue scale (VAS) and the Western Ontario and McMaster Universities osteoarthritis index score (WOMAC). Statistical analyses were performed using relevant parametric or non‐parametric tests. Results In total, 138 patients with KOA were included in this study. There were no significant differences in gender, age, and incidence of chronic residual pain after arthroscopy among the four groups (p > 0.05). The proportion of patients undergoing subsequent knee arthroplasty during the 2‐year follow‐up period was significantly higher in the Ow‐CS group (20/35) than in the Lw‐CS group (12/39) (p < 0.05). The K‐L rating showed an overall increasing trend over time, with the K‐L rating in the Ow‐N and Ow‐CS groups significantly higher than that in the Lw‐CS group at the final follow‐up (p < 0.05). VAS and WOMAC scores significantly decreased at 1 and 3 months post‐arthroscopy and then increased. One month after arthroscopy, VAS was significantly lower (p < 0.05) in the intra‐articular chitosan injection groups (Lw‐CS and Ow‐CS) compared with the non‐injection groups (Lw‐N and Ow‐N). VAS was lower in the Ow‐CS group than in the Lw‐CS group (p < 0.05). There was no significant difference in WOMAC between the intra‐articular chitosan injection and non‐injection groups at each time point (Lw‐N vs. Lw‐CS, Ow‐N vs. Ow‐CS, p > 0.05). Conclusion Arthroscopic surgery combined with intra‐articular chitosan injection shows short‐term positive effects in treating KOA. Intra‐articular chitosan injection appears to have a greater short‐term pain relief effect in obese patients.

Background: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. Methods: Sixty patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scoring, and American Knee Society (AKS) scoring were conducted. Results: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the presurgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced more reductions in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. Conclusion: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.

Purpose The purpose of this study was to predict the probability of postoperative pulmonary infection in elderly patients with hip fractures by developing and validating a precise model. Methods The clinical data of 1008 elderly hip fracture patients undergoing surgical treatment in Shanghai Tenth Peoples’ Hospital were retrospectively selected. A univariate analysis and multivariate regression were used to analyze the independent risk factors for postoperative pulmonary infection in elderly patients with hip fractures. A risk prediction model was established, and a nomogram was drawn. The area under the ROC curve and Hosmer‒Lemeshow test were used to evaluate the predictive effect of the model. Results The multivariate regression analysis indicated that age > 73, time from fracture to surgery (d) > 4 days, smoking, ASA ≥ III level, COPD, hypoproteinemia, red cell distribution width > 14.8%, mechanical ventilation time > 180 min, and stay in the ICU were independent risk factors for postoperative pulmonary infection in elderly patients. The AUCs of the model were 0.891 and 0.881, 0.843, respectively, in the two verification groups. For the Hosmer‒Lemeshow test, the P values were 0.726 in the modeling group and 0.497 and 0.231 in the verification group ( P > 0.05). Conclusion Overall, this study uncovered different independent risk factors for postoperative pulmonary infection in patients with hip fractures. The nomogram can effectively predict the occurrence of postoperative pulmonary infection.

Tendinopathy is the leading sports-related injury and will cause severe weakness and tenderness. Effective therapy for tendinopathy remains limited, and extracellular vesicles (EVs) derived from adipose tissue-derived mesenchymal stem cells (ADMSCs) have demonstrated great potential in tendinopathy treatment; however, the influence of aging status on EV treatment has not been previously described.In this study, it was found that ADMSCs derived from old mice (ADMSCold) demonstrated remarkable cellular senescence and impaired NAD+ metabolism compared with ADMSCs derived from young mice (ADMSCyoung). Lower NAMPT contents were detected in both ADMSCold and its secreted EVs (ADMSCold-EVs). Advanced animal experiments demonstrated that ADMSCyoung-EVs, but not ADMSCold-EVs, alleviated the pathological structural, functional and biomechanical properties in tendinopathy mice. Mechanistic analyses demonstrated that ADMSCyoung-EVs improved cell viability and relieved cellular senescence of tenocytes through the NAMPT/SIRT1/PPARγ/PGC-1α pathway. ADMSCyoung-EVs, but not ADMSCold-EVs, promoted phagocytosis and M2 polarization in macrophages through the NAMPT/SIRT1/Nf-κb p65/NLRP3 pathway. The macrophage/tenocyte crosstalk in tendinopathy was influenced by ADMSCyoung-EV treatment and thus it demonstrated "One-Stone-Two-Birds" effects in tendinopathy treatment.This study demonstrates an effective novel therapy for tendinopathy and uncovers the influence of donor age on curative effects by clarifying the detailed biological mechanism.

This study aims to analyse the pathological features of skeletal muscle injury repair by using rats to model responses to different exercise intensities. Eighty-four rats were randomly divided into five groups for treadmill exercise. The short-term control, low-intensity, medium-intensity and high-intensity groups underwent gastrocnemius muscle sampling after 6, 8 and 12 weeks of exercise. The long-term high-intensity group underwent optical coherence tomography angiography and sampling after 18 weeks of exercise. RNA sequencing was performed on the muscle samples, followed by the corresponding histological staining. Differentially expressed genes were generally elevated at 6 weeks in the early exercise stage, followed by a decreasing trend. Meanwhile, the study demonstrated a negative correlation between time and the gene modules involved in vascular regulation. The modules associated with muscle remodelling were positively correlated with exercise intensity. Although the expression of many genes associated with common angiogenesis was downregulated at 8, 12 and 18 weeks, we found that muscle tissue microvessels were still increased, which may be closely associated with elevated sFRP2 and YAP1. During muscle injury-remodelling, angiogenesis is characterized by significant exercise time and exercise intensity dependence. We find significant differences in the spatial distribution of angiogenesis during muscle injury-remodelling, which be helpful for the future achievement of spatially targeted treatments for exercise-induced muscle injuries.

The purpose of this study was to investigate the associations between gluteal muscle contracture (GMC) severity and patellofemoral instability and evaluate the reliability of novel indicators by multivariate analysis. Clinical and imaging data from 115 patients with GMC were collected for retrospective analysis. Two novel indicators were used to evaluate GMC severity (knee flexion angle and hip flexion angle, feet distance), and two additional novel parameters were used to reflect patellofemoral instability [patellar displacement vector (L, α), patella-femoral trochlear (P-FT) area, and femoral-trochlear-patella (FT-P) area]. In this study, patients with moderate contracture were dominant, and 35.65% also experienced anterior knee pain after physical activity. Ordered logistic regression analysis indicated that a more serious GMC represented a higher risk of lateral tilt and lateral displacement of the patella. Multivariate analysis showed that feet distance was a reliable indicator for evaluating the severity of GMC. The results showed that the more serious the GMC, the more significant the difference between the P-FT area and the FT-P area of the patellofemoral joint space. L, patellar tilt angle, patellar congruency angle, and lateral patellofemoral angle were independent risk factors for this difference. A more serious GMC represents a higher risk of patellar subluxation.

Osteosarcoma, occurring most frequently in children, teens, and young adults, is a lethal bone cancer with a high incidence of distant metastases and drug resistance. Developing a therapeutic platform that integrates targeting, curing and imaging is highly desirable for enhanced osteosarcoma therapy, yet quite challenging. In this work, we demonstrate a novel biomineralization-inspired strategy for the synthesis of a fructose incorporated manganese phosphate (Fru-MnP) nanoplatform for tumour targeting, drug-free therapy, and MRI imaging. Benefitting from the glucose transporter 5 (GLUT5)-mediated endocytosis, our Fru-MnP nanoplatform produces a high level of reactive oxygen species (ROS) via the Mn2+-driven Fenton reaction within osteosarcoma cells, leading to efficient cancer cell killing due to caspase-mediated apoptosis. By virtue of the T1 signal enhancement of Mn2+, our Fru-MnP nanoplatform also acts as an effective tumour-specific MRI contrast agent, realizing the MRI-monitored chemodynamic therapy. The proposed synergistic therapeutic platform opens new possibilities for high efficacy therapy for osteosarcoma.

The formation and metabolic balance of bone tissue is a controllable process of biomineralization, which is regulated by various cells, biomolecules, and ions. Enzyme molecules play an important role in this process, and alkaline phosphatase (ALP) is one of the most critical factors. In this study, inspired by the process of bone biomineralization, a biomimetic strategy is achieved for the preparation of mineralized ALP nanoparticles (MALPNs), by taking advantages of the unique reaction between ALP and calcium ions in Dulbecco's modified Eagle's medium. Benefiting from the mild biomineralization reaction, the MALPN system highly maintains the activity of ALP. Furthermore, the in vitro studies show that the MALPN system significantly enhances the proliferation of bone marrow mesenchymal stem cells and upregulates their osteogenic differentiation. When evaluated as synthetic graft materials for bone regeneration, the MALPN-incorporated gelatin methacryloyl graft shows excellent mechanical properties, a sustained release profile of ALP, and high biocompatibility and efficacy in guiding bone regeneration and vascularization for critical-sized rat calvarial defect. Moreover, we also demonstrate that the biomimetic mineralization strategy can be adopted for other proteins such as acid phosphatase, bovine serum albumin, fibrinogen, and gelatin, suggesting its universality for constructing mineralized protein-/enzyme-based bioactive materials for the application of tissue regeneration.

Rupture of tendons and ligaments (T/L) is a major clinical challenge due to T/L possess anisotropic mechanical properties and hierarchical structures. Here, to imitate these characteristics, an approach is presented by fabricating hybrid nanofibrous composites. First, hybrid fiber-reinforced yarns are fabricated via successively electrospinning poly(L-lactide-co-ε-caprolactone) (PLCL) and gelatin (Ge) nanofibers onto polyethylene terephthalate (PET) fibers to improve biodurability and biocompatibility. Then, by comparing different manufacturing methods, the knitted structure succeeds in simulating anisotropic mechanical properties, even being stronger than natural ligaments, and possessing comfort compliance superior to clinically used ligament advanced reinforcement system (LARS) ligament. Moreover, after inoculation with tendon-derived stem cells and transplantation in vivo, hybrid nanofibrous composites are integrated with native tendons to guide surrounding tissue ingrowth due to the highly interconnected and porous structure. The knitted hybrid nanofibrous composites are also ligamentized and remodeled in vivo to promote tendon regeneration. Specifically, after the use of optimized anisotropic hybrid nanofibrous composites to repair tendon, the deposition of tendon-associated extracellular matrix proteins is more significant. Thus, this study indicates a strategy of manufacturing anisotropic hybrid nanofibrous composites with superior mechanical properties and good histocompatibility for clinical reconstruction.

Background:Rotator cuff injury is the most common clinical shoulder joint disease, accounting for 50%-85% of all shoulder joint diseases. At present, arthroscopic rotator cuff repair has replaced the traditional surgical plan of incision and suture, becoming the first choice of surgeons. Its effectiveness and safety have been recognized in the industry. However, there are also occasional cases with poor postoperative effects and insufficient pain relief.Objective:To analyze the prognostic factors of arthroscopy rotator cuff repair.Methods:From February 2019 to February 2020, the primary data of 117 patients who received arthroscopic rotator cuff repair in the department of orthopedics of tenth people's hospital of Tongji university were retrospectively analyzed, and the surgical efficacy was followed up for one year after surgery.Results:There were 95 patients with a good prognosis, accounting for 81.20%. Multivariate analysis showed that age, preoperative course of the disease, degree of tear, and the use of platelet-rich plasma (PRP) were independent factors affecting prognosis.Conclusion:The age, preoperative course of the disease, rotator cuff tear degree, use of PRP during operation are important factors affecting the prognosis of arthroscopy rotator cuff repair.

目的 探讨非手术和关节镜手术治疗不同类型外侧型弹响髋的临床效果.方法 回顾性分析2016年2月至2017年11月在我科连续接受非手术治疗和关节镜手术治疗的94例四种不同类型的外侧型弹响髋患者的临床资料,男44例,女50例;年龄19～40岁,平均(29.8±5.25)岁.其中3例为单侧弹响,其余91例均为双侧.比较非手术治疗和关节镜手术治疗的效果以及优良率.结果 非手术治疗的总体有效率为13.8％,而关节镜手术治疗对所有患者均有效(100％).非手术治疗在Ⅰ型患者中的有效率明显高于Ⅱ型、Ⅲ型、Ⅳ型患者(P＜0.05),而关节镜手术治疗的有效率及优良率在四种类型患者之间差异无统计学意义(P＞0.05),且关节镜手术治疗相对于非手术治疗的患者有着更高的优良率(P＜0.05).结论 非手术治疗对Ⅰ型患者比Ⅱ型、Ⅲ型、Ⅳ型患者更有效,而关节镜手术治疗对四种类型患者均有效.我们推荐Ⅰ型患者首先选择非手术治疗,而Ⅱ型、Ⅲ型、Ⅳ型患者主要选择关节镜手术治疗,且在关节镜术后及时进行康复锻炼以便尽早恢复髋关节功能.

Background: This study aimed to investigate the correlation between the Alarmin S100A9 protein and Achilles tendinopathy (AT), and to reveal the role of this protein in inducing AT. Methods: In this study, 40 male Sprague-Dawley rats were randomly divided into four groups: Control group (received no treatment), Injury group (Achilles tendon tissues were cut intraoperatively), S100A9 group (received a subcutaneous injection of rhS100A9 solution), and S100A9 + Paquinimod group [received a subcutaneous injection of rhS100A9 and Paquinimod (1:1 ratio) into the Achilles tendon]. At 1 week postoperatively, the four groups of rats were euthanized, and the Achilles tendon tissues were isolated for histological staining, immunohistochemistry (IHC), immunofluorescence, Sirius Red (SR) staining, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Results: Compared with both the Control and S100A9 + Paquinimod groups, the Injury and S100A9 groups exhibited higher expression levels of S100A9 protein, matrix metalloproteinase-3 (MMP-3), and inflammatory factors. Regarding histomorphology [hematoxylin-eosin (HE) staining and Safranin O/fast green (SOFG; fast green and Safranin) training], the Achilles tendon tissues in the Injury and S100A9 groups showed AT-like changes, and the fibers were extremely disorderly, non-bundled, and ruptured, and some nuclei were spindles. As for collagen (Col) remodeling, a large number of fresh collagen fibers had formed, the amounts of Col-I and Col-II were lower, and a large quantity of Col-III was present. Additionally, a large number of tendon cells had died in both the Injury and S100A9 groups. Conclusions: This study showed that Alarmin S100A9 can induce AT-like morphological changes and local inflammatory reactions, trigger collagen fiber remodeling and tendon cell apoptosis, and ultimately induce AT.

As a noninvasive eye disease detection and drug delivery device, contact lenses can improve eye bioavailability and enable continuous drug delivery. In order to monitor the release of drugs in real time, molecularly imprinted contact lenses (MICLs) based on photonic crystals (PCs) were prepared for the treatment of diabetes-related diseases. The specific adsorption of molecularly imprinted polymers on dexamethasone sodium phosphate (DSP) increased the drug loading and optimized the drug release behavior. At the same time, the drug release ensures the rapid color report during the loading and releasing of drugs due to the volume and refractive index change of the hydrogel matrix. The continuous and slow release of DSP by MICLs in artificial tears was successfully monitored through structural color changes, and the cytotoxicity test results showed that the MICL had good biocompatibility. Therefore, MICLs with a PC structure color have great biomedical potentiality in the future.

臀肌挛缩症(ESH)发病机制与臀肌内反复接受注射药物(主要以青霉素为主)及特有的瘢痕体质等有关.其主要临床表现为髋关节功能障碍及骨盆倾斜变形.影像学检查中骶髂关节旁致密线影对于ESH诊断具有重要意义.ESH一旦保守治疗无效,患者症状无改善,均应早期行关节镜下松解术.该文就ESH诊治研究进展作一综述.

BackgroundSevere peripheral nerve injury leads to skeletal muscle atrophy and impaired limb function that is not sufficiently improved by existing treatments. Fibroblast growth factor 6 (FGF6) is involved in tissue regeneration and is dysregulated in denervated rat muscles. However, the way that FGF6 affects skeletal muscle repair after peripheral nerve injury has not been fully elucidated.MethodsIn this study, we investigated the role of FGF6 in the regeneration of denervated muscles using myoblast cells and an in vivo model of peripheral nerve injury.ResultsFGF6 promoted the viability and migration of C2C12 and primary myoblasts in a dose-dependent manner through FGFR1-mediated upregulation of cyclin D1. Low concentrations of FGF6 promoted myoblast differentiation through FGFR4-mediated activation of ERK1/2, which upregulated expression of MyHC, MyoD, and myogenin. FGFR-1, FGFR4, MyoD, and myogenin were not upregulated when FGF6 expression was inhibited in myoblasts by shRNA-mediated knockdown. Injection of FGF6 into denervated rat muscles enhanced the MyHC-IIb muscle fiber phenotype and prevented muscular atrophy.ConclusionThese findings indicate that FGF6 reduces skeletal muscle atrophy by relying on the ERK1/2 mechanism and enhances the conversion of slow muscle to fast muscle fibers, thereby promoting functional recovery of regenerated skeletal muscle after innervation.

The authors have requested that this preprint be withdrawn due to erroneous posting.

BACKGROUND Tranexamic acid (TXA) is safe and effective in total knee arthroplasty (TKA) for the prevention of bleeding. However, the role of TXA during unicompartmental knee arthroplasty (UKA) remains unclear. This study aimed to compare operative blood loss in patients undergoing UKA treated with an intra-articular injection of TXA with controls undergoing UKA without TXA. MATERIAL AND METHODS The prospective study included 101 patients who underwent UKA between January 2014 to March 2018. All patients completed a preoperative routine examination and were randomized to the study group (n=54) and the control group (n-47). The study group was given an articular injection of TXA (1.5 g in 50 ml normal saline) after the fascia was closed; the control group was injected with the same volume of normal saline. Blood volumes were measured from the drainage tube of the two groups during 48 hours. Total blood loss, postoperative drainage, hidden blood loss, blood transfusion rates, postoperative hemoglobin values, indicators of coagulation function, and the rates of wound complications were recorded. RESULTS Total blood loss in the study group was 745.6±105.1 ml, total drainage volume was 353.9±79.5 ml, and the hidden blood loss was 391.7±80.5 ml, which were all significantly lower when compared with the control group (P<0.05). None of the patients in the two groups suffered complications of surgery. CONCLUSIONS Intra-articular injection of TXA significantly reduced the total blood loss in patients who underwent UKA and did not increase the rate of complications.

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BackgroundGluteal muscle contracture (GMC) is a notable problem in some developing countries and includes features such as a snapping sound of the hip, abnormal gait, and unusual posture when patients squat with the knees together. Arthroscopic release can not only resolve symptoms, as previously reported, but can also greatly improve accompanying patellofemoral instability. This study was conducted to evaluate the effect of arthroscopic release of GMC on patellofemoral instability and its underlying mechanism.MethodsA total of nearly 500 patients who underwent arthroscopic release of GMC over 2.5years were filtered, and 54 patients were enrolled in the study. The selected research subjects all had combined patellofemoral instability preoperatively. The Lysholm scores and CT scans of the knee were evaluated pre- and postoperatively.ResultsThe mean follow-up time was 12.2months. All of the surveyed patients had satisfactory clinical outcomes for hip snapping sounds and abnormal gait. In addition, a significant difference (p<0.05) was observed between pre- and postoperative Lysholm scores, along with significant knee pain relief. Furthermore, the changes in CT scan parameters were significant as well. The average patellar tilt angle (PTA), patellofemoral index (PFI), and lateral patellar displacement (LPD) were obviously decreased (p<0.05) after the release. Conversely, the mean lateral patellofemoral angle (LPFA) showed a clear difference (p<0.05) between preoperative and postoperative CT examinations.ConclusionsArthroscopic release of GMC can reduce the tilt and lateral shift of the patella and enhance its stability due to the release of the iliotibial band.