Posterior cruciate ligament tibial attachment sacrifice percentage is higher in cruciate-retaining total knee arthroplasty in patients with discoid lateral meniscus.

BACKGROUND: The posterior cruciate ligament (PCL) attachment may be damaged in cruciate-retaining total knee arthroplasty (CR-TKA) using the complete resection for tibial preparation, and resection amount varies greatly among individuals. Discoid lateral meniscus (DLM) is one of the most common anatomic knee variants. This study aimed to evaluate the difference in PCL attachment sacrifice in CR-TKA between patients with and without DLM. METHODS: Fifty-one knees in the study group (DLM group) were matched 1:1 to 51 control knees (non-DLM group) by age, sex, and maximum width of the tibial plateau. The percentage of the sacrificed PCL attachment and the morphological parameters of the tibial plateau were evaluated using magnetic resonance imaging (MRI) in a blind manner. RESULTS: With a tibial cut simulated at a 0°, 3°, and 7° osteotomy slope, the mean PCL attachment resection percentages in the non-DLM group were 40.5%, 53.6%, and 72.6%, respectively. The corresponding resection percentages in the DLM group were 61.0% (P < 0.001), 73.3% (P < 0.001), and 85.7% (P < 0.001), respectively. The percentage of the minimum meniscus width to the maximum tibia width showed a weak positive correlation with the percentage of PCL attachment sacrifice. CONCLUSIONS: A significantly greater portion of PCL attachment was sacrificed in DLM patients undergoing CR-TKA using the complete proximal tibia resection. Attention should be paid to PCL attachment resection during CR-TKA in patients with DLM, and alternative techniques or prosthesis types should be considered.

Novel serum proteomic biomarkers for early diagnosis and aggressive grade identification of prostate cancer.

Background: Prostate cancer (PCa) is one of the most common tumors and the second leading cause of cancer-related death in men. The discovery of novel biomarkers for PCa diagnosis in the early stage, as well as discriminating aggressive PCa from non-aggressive PCa continue to pose a challenge. The aim of this study was to identify serum proteins that were sensitive and specific enough to detect early-stage and aggressive PCa. Methods: The serum proteomic profiling of patients with PCa and benign prostatic hyperplasia (BPH) was comprehensively analyzed using data-independent acquisition mass spectrometry (DIA-MS), and the bioinformatics analysis was performed. The differentially expressed proteins (DEPs) of interest were further verified by enzyme-linked immunosorbent assay (ELISA) and immunoturbidimetry assay. Results: Statistically significant difference in abundance showed 56 DEPs between early-stage PCa and BPH and 47 DEPs between aggressive and non-aggressive PCa patients. In addition, the verification results showed that serum L-selectin concentration was significantly higher (p<0.05) in Gleason 6 PCa when compared with BPH, and the concentration of osteopontin (SPP1) and ceruloplasmin (CP) increased with higher Gleason score. Conclusions: DIA-MS has great potential in cancer-related biomarker screening. Our data demonstrated that adding SPP1 and CP to PSA improved the separation of Gleason 7 (4 + 3) or above from Gleason 7 (3 + 4) or below compared with PSA diagnosis alone. Serum SPP1 and CP could be effective biomarkers to differentiate aggressive PCa (especially Gleason 7 (4 + 3) or above) from non-aggressive disease.

Recent Advances in Multifunctional Hydrogels for the Treatment of Osteomyelitis.

Osteomyelitis (OM), a devastating disease caused by microbial infection of bones, remains a major challenge for orthopedic surgeons. Conventional approaches for prevention and treatment of OM are unsatisfactory. Various alternative strategies have been proposed, among which, hydrogel-based strategies have demonstrated potential due to their unique properties, including loadable, implantable, injectable, printable, degradable, and responsive to stimuli. Several protocols, including different hydrogel designs, selection of antimicrobial agent, co-administration of bone morphogenetic protein 2 (BMP 2), and nanoparticles, have been shown to improve the biological properties, including antimicrobial effects, osteo-induction, and controlled drug delivery. In this review, we describe the current and future directions for designing hydrogels and their applications to improve the biological response to OM in vivo.

3D-Printed Hydrogels in Orthopedics: Developments, Limitations, and Perspectives.

Three-dimensional (3D) printing has been used in medical research and practice for several years. Various aspects can affect the finished product of 3D printing, and it has been observed that the impact of the raw materials used for 3D printing is unique. Currently, hydrogels, including various natural and synthetic materials, are the most biologically and physically advantageous biological raw materials, and their use in orthopedics has increased considerably in recent years. 3D-printed hydrogels can be used in the construction of extracellular matrix during 3D printing processes. In addition to providing sufficient space structure for osteogenesis and chondrogenesis, hydrogels have shown positive effects on osteogenic and chondrogenic signaling pathways, promoting tissue repair in various dimensions. 3D-printed hydrogels are currently attracting extensive attention for the treatment of bone and joint injuries owing to the above-mentioned significant advantages. Furthermore, hydrogels have been recently used in infection prevention because of their antiseptic impact during the perioperative period. However, there are a few shortcomings associated with hydrogels including difficulty in getting rid of the constraints of the frame, poor mechanical strength, and burst release of loadings. These drawbacks could be overcome by combining 3D printing technology and novel hydrogel material through a multi-disciplinary approach. In this review, we provide a brief description and summary of the unique advantages of 3D printing technology in the field of orthopedics. In addition, some 3D printable hydrogels possessing prominent features, along with the key scope for their applications in bone joint repair, reconstruction, and antibacterial performance, are discussed to highlight the considerable prospects of hydrogels in the field of orthopedics.

tRNA derived fragment (tRF)-3009 participates in modulation of IFN-α-induced CD4+ T cell oxidative phosphorylation in lupus patients.

BACKGROUND: Accumulating evidence suggests tRNA-derived fragments (tRFs) play important roles in cellular homeostasis. Here we aimed to explore aberrant expression of tRFs in CD4+ T cells from patients with systemic lupus erythematosus (SLE) and their potential function in the SLE pathogenesis. METHODS: First, small RNA sequencing was performed on CD4+ T cells from four SLE patients and three healthy controls (HCs). Candidate tRFs were then validated in CD4+ T cells from 97 SLE patients and their relevant disease controls using qRT-PCR. Then sequencing was used to investigate the profiles of HC-derived CD4+ T cells transfected with tRF-3009. Lastly, tRF-3009 siRNA or tRF-3009 mimics were transfected into CD4+ T cells with/without IFN-α. Changes in oxygen consumption rate (OCR), ATP, and ROS production were analyzed. RESULTS: We identified 482 differentially expressed tRFs from SLE CD4+ T cells and chose tRF-3009 for further analysis due to its upregulation and the positive correlations between its expression and SLEDAI, active lupus nephritis and serum IFN-α levels. In vitro, tRF-3009 over-expressing CD4+ T cell profiling and putative analysis linked this product to the type I IFN and oxidative phosphorylation (OXPHOS) pathways. Interestingly, IFN-α is capable of inducing ROS and ATP production in CD4+ T cells, while knockdown of tRF-3009 reversed this process. Overexpression of tRF-3009 in CD4+ T cells alone was sufficient to upregulate OCR, ROS, and ATP production. CONCLUSIONS: Our study is the first to link aberrant tRF expression and SLE. tRF-3009 may participate in metabolic modulation of IFN-α-induced CD4+ T cell OXPHOS in lupus.

A low-temperature-printed hierarchical porous sponge-like scaffold that promotes cell-material interaction and modulates paracrine activity of MSCs for vascularized bone regeneration.

Mesenchymal stem cells (MSCs) secrete paracrine trophic factors that are beneficial for tissue regeneration. In this study, a sponge-like scaffold with hierarchical and interconnected pores was developed using low-temperature deposition modeling (LDM) printing. Its effects on the cellular behavior, especially on the paracrine secretion patterns of MSCs, were comprehensively investigated. We found that compared with the scaffolds printed via the fused deposition modeling (FDM) technique, the LDM-printed sponges enhanced the adhesion, retention, survival, and ingrowth of MSCs and promoted cell-material interactions. Moreover, the paracrine functions of the cultured MSCs on the LDM-printed sponges were improved, with significant secretion of upregulated immunomodulatory, angiogenic, and osteogenic factors. MSCs on the LDM-printed sponges exert beneficial paracrine effects on multiple regenerative processes, including macrophage polarization, tube formation, and osteogenesis, verifying the enhanced immunomodulatory, angiogenic, and osteogenic potential. Further protein function assays indicated that focal adhesion kinase (FAK), downstream AKT, and yes-associated-protein (YAP) signaling might participate in the required mechanotransductive pathways, through which the hierarchical porous structures stimulated the paracrine effects of MSCs. In a rat distal femoral defect model, the MSC-laden LDM-printed sponges significantly promoted vascularized bone regeneration. The results of the present study demonstrate that the hierarchical porous biomimetic sponges prepared via LDM printing have potential applications in tissue engineering based on their cell-material interaction promotion and MSC paracrine function modulation effects. Furthermore, our findings suggest that the optimization of biomaterial properties to direct the paracrine signaling of MSCs would enhance tissue regeneration.

MCOLN1 Promotes Proliferation and Predicts Poor Survival of Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: MCOLN1 (mucolipin subfamily, member 1) was first identified as an autophagic regulator, which was essential for efficient fusion of both autophagosomes and late endosomes with lysosomes. This study is aimed at investigating the role of MCOLN1 in the development of pancreatic ductal adenocarcinoma (PDAC). METHODS: Immunohistochemistry (IHC) assay was conducted to evaluate the expression level of MCOLN1 in 82 human PDAC tumor tissues. Overall survival (OS) and recurrence-free survival (RFS) analysis was performed to assess the prognosis of patients. Colony formation and MTT assays [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] were performed to measure the proliferation capacity of tumor cells. The expression level of related genes was measured by RT-PCR (reverse transcription polymerase chain reaction) and western blot assays. The animal model was used to examine the effects of indicated protein on tumorigenesis in vivo. RESULTS: The results of IHC showed that a high level of MCOLN1 expression was associated with the poor clinical characteristics of PDAC patients. OS and RFS were significantly worse in patients with high MCOLN1 expression. Silencing of MCOLN1 dramatically blocked the proliferation of PDAC cells. Mechanism studies confirmed that knockdown of MCOLN1 decreased the expression of Ki67 and PCNA (proliferating cell nuclear antigen), two markers of cell proliferation. In vivo, MCOILN1 depletion reduced the formation and growth of tumors in mice. CONCLUSION: The high level of MCOLN1 expression was associated with poor clinical outcomes of PDAC patients. MCOLN1 ablation could inhibit PDAC proliferation of both in vitro and in vivo, which provide a new insight and novel therapeutic target for the treatment of PDAC.

A multidisciplinary clinic approach to improve physician-related diagnostic delay for patients with axial spondyloarthritis: a retrospective study.

OBJECTIVE: To assess the diagnostic delay (DD) and physician-related DD (pDD) in patients with axial spondyloarthritis (SpA) and the potential benefits of a multidisciplinary clinic (MDC) approach. METHODS: A retrospective study was undertaken among patients with axial SpA, which aimed to analyse DD, pDD and their risk factors. The influence of pDD on disease outcomes was examined. The pDDs among consecutive SpA patients in an MDC cohort were compared with propensity score matched historical controls (1:1). RESULTS: A total of 208 patients with axial SpA formed the historical control group and 49 patients with axial SpA formed the MDC cohort after introduction of the MDC. The median DD and pDD in the historical controls were 25.5 and 10.0 months, respectively. A cut-off of pDD > 4 months was associated with more active disease and functional impairment. An initial visit to a non-rheumatologist was the most significant risk factor for pDD. Following MDC introduction, the median pDD decreased from 13 months to 1 month after adjustments were made for confounders such as sex, education level, history of smoking, human leukocyte antigen-B27 status and SpA/ankylosing spondylitis classification criteria. CONCLUSION: The MDC was a promising approach that resulted in a reduced pDD among patients with axial SpA.

Overexpression of miR­146a blocks the effect of LPS on RANKL­induced osteoclast differentiation.

The concept that inflammation serves a leading role in osteoclast­induced bone loss under pathological circumstances is now widely accepted. In the present study, it was observed that lipopolysaccharides (LPSs) demonstrated a synergic effect on receptor activator of nuclear factor κ­B ligand (RANKL)­induced osteoclast differentiation in Raw264.7 cells, with increasing levels of multiple pro­inflammatory cytokines including interleukin (IL)­6, tumor necrosis factor­α and IL­1ß. Furthermore, microRNA (miR)­146a was highly induced by LPS and RANKL co­stimulation during the process of osteoclast differentiation. Overexpression of miR­146a inhibited osteoclast transformation by targeting the key regulators of nuclear factor (NF)­κß signaling, TNF receptor­associated factor 6 and interleukin­1 receptor­associated kinase 1. The downstream activation of NF­κß signaling was also inhibited by transfection with a miR­146a mimic. Altogether, the results of the present study demonstrated that miR­146a prevents osteoclast differentiation induced by LPS and RANKL co­stimulation, suggesting that miR­146a may be a promising therapeutic target for treatment of inflammation mediated bone loss.