Mechanical stress plays an important role in the initiation and progression of osteoarthritis. Studies show that excessive mechanical stress can directly damage the cartilage extracellular matrix and shift the balance in chondrocytes to favor catabolic activity over anabolism. However, the underlying mechanism remains unknown. MicroRNAs (miRNAs) are emerging as important regulators in osteoarthritis pathogenesis. We have found that mechanical loading up-regulated microRNA miR-365 in growth plate chondrocytes, which promotes chondrocyte differentiation. Here, we explored the role of the mechanical responsive microRNA miR-365 in pathogenesis of osteoarthritis (OA). We found that miR-365 was up-regulated by cyclic loading and IL-1β stimulation in articular chondrocytes through a mechanism that involved the transcription factor NF-κB. miR-365 expressed significant higher level in rat anterior cruciate ligament (ACL) surgery induced OA cartilage as well as human OA cartilage from primary OA patients and traumatic OA Patients. Overexpression of miR-365 in chondrocytes increases gene expression of matrix degrading enzyme matrix metallopeptidase 13 (MMP13) and collagen type X (Col X). The increase in miR-365 expression in OA cartilage and in response to IL-1 may contribute to the abnormal gene expression pattern characteristic of OA. Inhibition of miR-365 down-regulated IL-1β induced MMP13 and Col X gene expression. We further showed histone deacetylase 4 (HDAC4) is a direct target of miR-365, which mediates mechanical stress and inflammation in OA pathogenesis. Thus, miR-365 is a critical regulator of mechanical stress and pro-inflammatory responses, which contributes cartilage catabolism. Manipulation of the expression of miR-365 in articular chondrocytes by miR-365 inhibitor may be a potent therapeutic target for the prevention and treatment of osteoarthritis.

Most studies on grafts for anterior cruciate ligament (ACL) reconstruction (ACLR) have been of autografts or nonirradiated allografts with a single-bundle (SB) technique. Outcome reports evaluating anatomic double-bundle (DB) ACLR with a hamstring tendon autograft versus irradiated allograft are rare. To compare the clinical outcomes of arthroscopic anatomic DB ACLR with a hamstring tendon autograft versus irradiated allograft. Randomized controlled trial; Level of evidence, 2. Between 2008 and 2009, a total of 107 patients undergoing arthroscopic DB ACLR were prospectively randomized consecutively into 1 of 2 groups (autograft [Auto] group and irradiated allograft [Ir-Allo] group). All the surgical procedures were performed by the same senior surgeon using the DB reconstruction technique. All irradiated hamstring tendon allografts were sterilized with 2.5 Mrad of irradiation before distribution and were obtained from a single certified tissue bank. Graft fixation on the femoral side was by an Endobutton, and on the tibial side by a bioabsorbable interference screw augmented with a staple. The same rehabilitation protocol was applied to all patients. Before surgery and at a mean of 6.9 years of follow-up, patients were evaluated by the same observer according to objective and subjective clinical evaluations including detailed history, physical examination, radiography, functional knee ligament testing, KT-2000 arthrometer testing, Harner vertical jump and Daniel 1-legged hop tests, Lysholm score, Tegner score, International Knee Documentation Committee (IKDC) standard evaluation form, and Cincinnati knee score. A total of 83 patients (Auto: n = 40 [mean age, 29.2 ± 6.9 years]; Ir-Allo: n = 43 [mean age, 28.6 ± 7.2 years]) fulfilled follow-up and clinical evaluations. No significant differences were found between the 2 groups according to the overall IKDC functional and subjective evaluations as well as testing of activity levels. Significant between-group differences were found when comparing the results at final follow-up according to the Lachman test, anterior drawer test, pivot-shift test, and KT-2000 arthrometer measurements (P < .001). Most importantly, 87.5% of patients in the Auto group and 34.9% in the Ir-Allo group had a side-to-side difference 5 mm) with an irradiated allograft (30.2%) was higher than that with an autograft (7.5%) (P < .001). The failure rate in the Ir-Allo group (30.2%) was higher than that in the Auto group (7.5%) (P < .001). Anterior and rotational stability decreased significantly in the Ir-Allo group; patients in the Ir-Allo group also had a shorter operation time. There were 10.0% (4/40) of patients in the Auto group and 32.6% (19/43) of patients in the Ir-Allo group who had arthritic progression (P < .05). There were no significant differences in postoperative activity levels and functional outcomes between the Auto and Ir-Allo groups. However, a significant increase in anterior and rotational laxity in the Ir-Allo group was found according to evaluations. We do not advocate an irradiated hamstring tendon allograft for DB ACLR. Clinical Trial Register System of The Affiliated Hospital of Qingdao University (qdfy-ky2008-12)

Relative young and more active patients with osteoarthritis (OA) of the isolated medial femorotibial compartment in conjunction with anterior cruciate ligament (ACL) deficiency are difficult to treat. The aim of this study was to explore the early clinical outcomes of combined Oxford unicompartmental knee arthroplasty (UKA) and ACL reconstruction for the patients presenting ACL deficiency and isolated OA of the medial compartment. Twenty-eight patients were included into the study. All patients were treated by combined Oxford UKA and ACL reconstruction. Plain radiographs in the antero-posterior and lateral view and long-leg standing radiographs were routinely performed prior to and after surgery. Stress radiographs in valgus were additionally available in order to verify the well-preserved lateral compartment. The varus deformity of the knee prior to surgery and the valgus degree after surgery, the posterior slope of the tibial component and the range of motion (ROM) of the knee after surgery were measured and recorded. Clinical evaluations include Oxford Knee Score (OKS), Knee Society Score (KSS-clinical score; KSS-function score) and Tegner activity score. All the patients were followed up for 52 ± 8 months. The leg alignment showed 3.1 ± 0.6° of varus deformity prior to surgery and 4.0 ± 0.7° of valgus after surgery. The OKS, KSS and Tegner activity score improved significantly after surgery (P < 0.05). The mean ROM of the operated knee was 123.5 ± 2.8° at the last follow-up. The posterior slope of the tibial component was 3.9 ± 1.2°. A significant correlation was found between them according to the Pearson’s correlation (r = 0.39, P = 0.03). There were 2 patients (7 %) with the complication of mobile bearing dislocation, and a second operation of replacing a thicker mobile bearing was performed for them. The early clinical data have shown that combined surgery of UKA and ACL reconstruction has revealed promising results. However, long-term follow-up studies should be done in these patients. Current trial ISRCTN24663935 (Retrospectively registered on 21 July 2016).

Background: Tumor microenvironment (TME) plays an important role in malignant tumors. Our study aimed to investigate the effect of the TME and related genes in osteosarcoma patients.Methods: Gene expression profiles and clinical data of osteosarcoma patients were downloaded from the TARGET dataset. ESTIMATE algorithm was used to quantify the immune score. Then, the association between immune score and prognosis was studied. Afterward, a differential analysis was performed based on the high- and low-immune scores to determine TME-related genes. Additionally, Cox analyses were performed to construct two prognostic signatures for overall survival (OS) and disease-free survival (DFS), respectively. Two datasets obtained from the GEO database were used to validate signatures.Results: Eighty-five patients were included in our research. The survival analysis indicated that patients with higher immune score have a favorable OS and DFS. Moreover, 769 genes were determined as TME-related genes. The unsupervised clustering analysis revealed two clusters were significantly related to immune score and T cells CD4 memory fraction. In addition, two signatures were generated based on three and two TME-related genes, respectively. Both two signatures can significantly divide patients into low- and high-risk groups and were validated in two GEO datasets. Afterward, the risk score and metastatic status were identified as independent prognostic factors for both OS and DFS and two nomograms were generated. The C-indexes of OS nomogram and DFS nomogram were 0.791 and 0.711, respectively.Conclusion: TME was associated with the prognosis of osteosarcoma patients. Prognostic models based on TME-related genes can effectively predict OS and DFS of osteosarcoma patients.

Background: General anesthesia may counteract the neuroprotective effects of S-ketamine, so previous trials may have underestimated the efficacy of S-ketamine to reduce postoperative delirium (POD). The authors hypothesized that administration of S-ketamine in a non–general anesthesia setting would reduce the risk of POD. Methods: This study was conducted at a high-volume arthroplasty referral center where standardized, evidence-based perioperative protocols are implemented with high fidelity. This study included 372 elderly patients undergoing total hip or knee arthroplasty under neuraxial anesthesia. Patients were enrolled from November 2023 to October 2024, and in-person follow-up assessments were conducted from admission to 3 days after surgery. Patients were randomized to receive either S-ketamine (n = 186) or normal saline placebo (n = 186). The primary outcome was risk of POD within 3 days after surgery. Secondary outcomes were number of POD episodes, POD onset time and duration, POD severity, POD subtype, pain score (numeric rating scale), opioid consumption, number of patients requiring rescue analgesia, sleep quality, clinical outcomes, and harms. Results: Within 3 days after surgery, 15 patients in the S-ketamine group (8.06%) developed POD, compared to 38 patients (20.43%) in the placebo group (adjusted odds ratio, 0.29; 95% CI, 0.14 to 0.63; P = 0.002). On postoperative day 1, patients in the S-ketamine group experienced significantly less pain during exercise and physical therapy and had a lower incidence of rescue analgesia use compared to the placebo group. The incidence of hallucinations, dizziness, and nightmares was higher in the S-ketamine group than in the placebo group. The incidence of other complications was low in both groups, with no statistically significant differences. Conclusions: S-ketamine can reduce risk of POD in elderly patients undergoing total hip or knee arthroplasty under neuraxial anesthesia. However, generalizability of these findings may be limited due to the study’s setting.