To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.Aims
Methods
The surgical helmet system (SHS) was developed to reduce the risk of periprosthetic joint infection (PJI), but the evidence is contradictory, with some studies suggesting an increased risk of PJI due to potential leakage through the glove-gown interface (GGI) caused by its positive pressure. We assumed that SHS and glove exchange had an impact on the leakage via GGI. There were 404 arthroplasty simulations with fluorescent gel, in which SHS was used (H+) or not (H-), and GGI was sealed (S+) or not (S-), divided into four groups: H+S+, H+S-, H-S+, and H-S-, varying by exposure duration (15 to 60 minutes) and frequency of glove exchanges (0 to 6 times). The intensity of fluorescent leakage through GGI was quantified automatically with an image analysis software. The effect of the above factors on fluorescent leakage via GGI were compared and analyzed.Aims
Methods
Osteoporosis is a common problem in postmenopausal women and the elderly. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates glucocorticoids (GCs) in vivo, which is a considerable potential target as treatment for osteoporosis. Previous studies have demonstrated its effect on osteogenesis, and our study aimed to demonstrate its effect on osteoclast activation. In vivo, we used 11β-HSD1 knock-off (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, In vivo, We used 11β-HSD1 knockoff (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, bone marrow-derived macrophages (BMM) and bone marrow mesenchymal stem cell (BMSC) of KO and C57BL6/J mice were extracted to test their osteogenic and osteoclastic abilities. We then created osteoclastic 11β-HSD1 elimination mice (Ctsk::11β-HSD1fl/fl) and treated them with OVX. Micro-CT analysis, H&E, immunofluorescence staining, and qPCR were performed. Finally, we conducted the high-throughput sequencing to find out 11β-HSD1 and osteoclast activation related genes. We collected 6w samples after modeling. We found that KO mice were resistant to loss of bone trabeculae. The same effect was observed in osteoclastic 11β-HSD1 elimination mice. Meanwhile, BVT-2733, a classic inhibitor of 11β-HSD1, inhibited the osteoclast effect of cells without affecting osteogenic effect in vitro. High-throughput sequencing suggested that glucocorticoid receptor (GR) may play a key role in the activation of osteoclasts, which was verified by immunofluorescence staining and WB in vivo and in vitro. In the process of osteoporosis, 11β-HSD1 expression of osteoclasts is abnormally increased, which may be a new target for inhibiting osteoclast activation and treating osteoporosis.
Lumbar diseases have become a major problem affecting human health worldwide. Conservative treatment of lumbar diseases is difficult to achieve ideal results, and surgical treatment of trauma, complications, it is imperative to develop a new treatment method. This study aims to explore the regulatory mechanism of cartilage endplate ossification caused by abnormal stress, and design intervention targets for this mechanism, so as to provide theoretical reference for the prevention and treatment of lumbar degeneration. In vivo, we constructed spinal instability model in mice. In vitro, we used a mechanical tensile machine to simulate the abnormal stress conditions of the endplate cartilage cells. Through the high-throughput sequencing, we found the enrichment of Hippo signaling pathway. As YAP is a key protein in the Hippo signaling pathway, we then created cartilaginous YAP elimination mice (Col2::YAPfl/fl). The lumbar spine model was constructed again in these mice for H&E, SOFG and immunofluorescence staining. In vitro lentivirus was used to knock out YAP, immunofluorescence staining, WB and qPCR were performed. Finally, we conducted therapeutic experiments by using YAP agonist and AAV5 carrying YAP plasmids. We collected 8w samples from C57/BL6 mice after modeling. We found ossification of the endplate in mice similar to human disc degeneration. High-throughput sequencing of stretched cells demonstrated high enrichment of the Hippo signaling pathway. By immunofluorescence staining, it was confirmed that Col-II decreased and Col-X gradually increased in the endplate cartilage of mice. This was also confirmed at 7 days after an in vitro stretch of 5% and 12%. Meanwhile, we found that cartilaginous YAP elimination mice developed very severe endplate degeneration. However, the endplate was well protected by intraperitoneal injection of YAP agonist or AAV5-YAP endplate injection, and the results in vitro were consistent with that. In the process of cartilaginous ossification, abnormal stress regulates Col10a1 to promote cartilage endplate ossification through Hippo signaling pathway mediated YAP, and we expect to find potential drug targets for treatment through this mechanism.
Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of Aims
Methods
The purpose of this prospective pilot study is to examine the feasibility of a physiotherapist led rapid access shoulder screening clinic (RASC). The goal of this study is to assess for improvements in patient access to care, patient reported outcome measures, patient reported experience measures, and cost outcomes using time driven activity based costing methods. Patient recruitment began in January 2021. Consultation requests from general practitioners and emergency rooms are analyzed and triaged through a central system. One half of patients awaiting consultation were triaged to the traditional route used at our center while the other half were triaged to be assessed at the RASC. Outcome measures consisting of the Simple Shoulder Test and SF-12 were recorded at the initial consultation and at follow up appointments. Cost benefit analysis was conducted using time driven activity based costing methods (TD-ABC). From January to August of 2021, 123 new patients were triaged for RASC assessment. On average, the RASC gets 10 new referrals per month. As of September 2021, there are 65 patients still on waitlist for RASC assessment with 58 having been assessed. Of the 58, 11% were discharged through the RASC, 48% pursued private physiotherapy, 14% had injections, 19% proceeded on for surgical consultation, and 8% did not show. Over time same time period, approximately 15 new patients were seen in consultation by the surgeon's office. Thirty-five responses were obtained from RASC patients during their initial intake assessment. The average age of respondents was 54.7 with 21 females and 14 males. Median SF-12 scores in the physical dimension (PCS-12) for RASC patients were 36.82 and mental (MCS-12) 49.38927. Median Simple Shoulder Test scores measured 6. Of the patients who responded to the follow up questionnaires after completing physiotherapy at the RASC, both the SF-12 and Simple Shoulder Test scoring improved. Median PCS-12 measured 47.08, MCS-12 of 55.87, and Simple Shoulder Test measured 8. RASC assessments by PT saved $172.91 per hour for consultation and $157.97 per hour for patient follow ups. Utilization of a physiotherapy led rapid access shoulder clinic resulted in improvements in patient outcomes as measured by the SF-12 and Simple Shoulder Test as well as significant direct cost savings. Proper triage protocols to identify which patients would be suitable for RASC assessment, buy-in from physiotherapists, and timely assessment of patients for early initiation of rehabilitation for shoulder pain is paramount to the success of a RASC system at our centre. Future research direction would be geared to analyzing a larger dataset as it becomes available.
To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction. In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing.Aims
Methods
The aim of this study was to develop an open-source finite element model of the ankle for identification of the best clinical treatment to restore stability to the ankle after injury. The ankle geometry was defined from the Visible Human Project Female CT dataset available from the National Library of Medicine, and segmented using Dragonfly software (Object Research Systems, 2020). The finite element model was created with FEBio (University of Utah, 2021) using the dynamic nonlinear implicit solver. Linear isotropic material properties were assigned to the bones (E=7300MPa, ν=0.3, ρ=1730kg/m3) and cartilage (E=10MPa, ν=0.4, ρ=1100kg/m3). Spring elements were used to represent the ligaments and material properties were taken from Mondal et al. [1]. Lagrangian contact was defined between the cartilaginous surfaces with μ=0.003. A standing load case was modelled, assuming even distribution of load between the feet. A reaction force of 344.3N was applied to the base of the foot, a muscle force of 252.2N, and the proximal ends of the tibia and fibula were fully constrained.Abstract
Objectives
Methods
Direct ink writing (DIW) has gained considerable attention in production of personalized medical implants. Laponite nanoclay is added in polycaprolactone (PCL) to improve printability and bioactivity for bone implants. The 3D structure of DIW printed PCL/Laponite products was qualitatively evaluated using micro-CT. PCL/LP composite ink was formulated by dissolving 50% m/v PCL in dichloromethane with Laponite loading of up to 30%. The rheological properties of the inks were determined using Discovery HR-2 rheometer. A custom-made direct ink writer was used to fabricate both porous scaffold with 0°/90° lay-down pattern, and solid dumbbell-shaped specimens (ASTM D638 Type IV) with two printing orientations, 0° and 90° to the loading direction in tensile testing. The 3D structure of specimens was assessed using a micro-CT. Independent t-tests were performed with significance level at p<0.05.Abstract
Objectives
Methods
The objective of this study is to investigate the effect of solvents and rheological properties of PCL/Hydroxyapatite ink on the shape fidelity of the 3D printed scaffolds for bone tissue engineering. A series of inks were made consisting of 50% (w/v) of polycaprolactone (PCL) filled with 0%, 3.5% and 12.5% (w/V) of hydroxyapatite (HA) in dichloromethane (DCM) and chloroform (CHF). Steady and oscillatory shear rheological tests were performed on a rheometer (Discovery HR-3). Solvent-cast direct ink writing was performed with a custom-made 3D printer for the fabrication of PCL/HA scaffold structures with 2–8 layers. Optical microscope and scanning electron microscopy (SEM) were used to assess the shape fidelity.Abstract
Objectives
Methods
This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs.Aims
Methods
There is an increasing demand for hip arthroplasty in China. We aimed to describe trends in in-hospital mortality after this procedure in China and to examine the potential risk factors. We included 210 450 patients undergoing primary hip arthroplasty registered in the Hospital Quality Monitoring System in China between 2013 and 2016. In-hospital mortality after hip arthroplasty and its relation to potential risk factors were assessed using multivariable Poisson regression.Aims
Patients and Methods
Although most joint surgeons have reached a consensus that preoperative risk assessment and appropriate medical intervention for elderly patients of primary total hip arthrplasty (PTHA) could significantly reduce postoperative complications and mortality, there is still lack of a detailed and comprehensive approach for risk stratifying and a systematic method for risk allaying. We aimed to explore the risk factors related to the aggravation of preoperative complications and the appearance of complications post-operation of primary total hip arthrplasty (PTHA) in elderly patients for hip fracture. We retrospectively reviewed the demographic and clinical data of 156 patients who underwent PTHA for hip fracture from January 2014 to December 2016, of which there were 61 male (39.1%) and 95 female (60.9%) patients; 111 patients aged 60–79 years (71.2%) and 45 patients ≥ 80 years old (28.8%); 125 patients of femoral neck fracture (80.1%) and 31 patients of inter-trochanteric fracture (19.9%); 109 patients of spinal anesthesia (69.9%) and 48 patients of general anesthesia (30.1%); 85 patients undergoing surgery within 3 days (54.5%) and 71 patients operated ≥ 4 days (45.5%) since admission. We evaluated the correlations among gender, age, type of fracture, methods of anesthesia, time of operation since admission, the aggravation of preoperative complications and the appearance of postoperative complications post PTHA using the IBM SPSS Statistics (version 21) and the Exce1 2016.Objectives
Patients and methods
Soft tissue tension and intra-articular pressure distribution plays a crucial role in postoperative function and survivorship of TKA prosthesis. Although posterior stabilized (PS) and cruciate retaining (CR) knees have both been successful in relieving pain and restore function, it is reported that the joint gaps were significantly distinct between the two designs during flexion. The aim of this study is to find out what is the difference in intra-articular pressure distribution between PS and CR knees. We prospectively included 45 consecutive patients (50 knees) scheduled for total knee arthroplasty between August, 2013 and April, 2014 in our hospital. 23 patients (25 osteoarthritic knees) received a Genesis II CR TKA (Smith & Nephew, Memphis, USA), and the other 22 patients (25 osteoarthritic knees) received Genesis II PS TKA (Smith & Nephew, Memphis, USA). During operation, after the bone osteotomy and soft tissue balance were completed, we measured and compared the intra-articular pressure distribution at 0°, 30°, 45°, 60°, 90°, and 120° flexion with a previously validated “Wireless Force Measurement System (WFMS)”. Joint gaps were measured at extension and 90° flexion. The soft tissue was not considered balanced until the medial and lateral joint gap difference ≤ 2mm at extension and 90° flexion. There are no significant differences in age, gender, BMI, varus angle and flexion deformity, and preoperative range of motion between the two groups. The medial-lateral pressure distribution and total pressure were compared at different angles between CR and PS knees.Background
Methods
We evaluated the impact of lumbar instrumented
circumferential fusion on the development of adjacent level vertebral
compression fractures (VCFs). Instrumented posterior lumbar interbody
fusion (PLIF) has become a popular procedure for degenerative lumbar
spine disease. The immediate rigidity produced by PLIF may cause
more stress and lead to greater risk of adjacent VCFs. However,
few studies have investigated the relationship between PLIF and
the development of subsequent adjacent level VCFs. Between January 2005 and December 2009, a total of 1936 patients
were enrolled. Of these 224 patients had a new VCF and the incidence
was statistically analysed with other covariants. In total 150 (11.1%)
of 1348 patients developed new VCFs with PLIF, with 108 (72%) cases
at adjacent segment. Of 588 patients, 74 (12.5%) developed new subsequent
VCFs with conventional posterolateral fusion (PLF), with 37 (50%)
patients at an adjacent level. Short-segment fusion, female and
age older than 65 years also increased the development of new adjacent
VCFs in patients undergoing PLIF. In the osteoporotic patient, more
rigid fusion and a higher stress gradient after PLIF will cause
a higher adjacent VCF rate. Cite this article:
In a retrospective cohort study we compared the
clinical outcome and complications, including dysphagia, following
anterior cervical fusion for the treatment of cervical spondylosis
using either a zero-profile (Zero-P; Synthes) implant or an anterior
cervical plate and cage. A total of 83 patients underwent fusion
using a Zero-P and 107 patients underwent fusion using a plate and
cage. The mean follow-up was 18.6 months ( When compared with the traditional anterior cervical plate and
cage, the Zero-P implant is a safe and convenient procedure giving
good results in patients with symptomatic cervical spondylosis with
a reduced incidence of dysphagia post-operatively. Cite this article:
The consequences of breakdown of the wound after surgery to tendo Achillis are considerable. Complex surgery is often required to reconstruct the tendon and to provide soft-tissue cover. We describe a new incision which approaches the tendon by using a distally-based fasciocutaneous flap. This reduces the risk of breakdown of the wound since it avoids making an incision directly over the tendon, provides good exposure, and maintains the vascularity of the skin overlying the tendon.
We compared the mechanical properties of normal and reconstructed heel pads in seven patients. Four had latissimus dorsi flaps and one each an anterior thigh flap, a local dorsalis pedis flap and a sural arterial flap. The thickness of the heel pad was measured under serial incremental loads of 0.5 kg to a maximum of 3 kg and then relaxed sequentially. The load-displacement curve of the heel pad during a loading-unloading cycle was plotted and from this the unloaded heel-pad thickness (UHPT), compressibility index (CI), elastic modulus (Ep), and energy dissipation ratio (EDR) were calculated. The EDR was significantly increased in the reconstructed heels (53.7 ± 18%
