Transformer-based Multi-label Deep Learning Model is Efficient for Detecting Ankle Lateral and Medial Ligament Injuries on MRI and Improving Clinicians' Diagnostic Accuracy for Rotational Chronic Ankle Instability.

PURPOSE: To develop a deep learning (DL) model that can simultaneously detect lateral and medial collateral ligament injuries of the ankle, aiding in the diagnosis of chronic ankle instability (CAI), and assess its impact on clinicians' diagnostic performance. METHODS: DL models were developed and external validated on retrospectively collected ankle MRIs between April 2016 and March 2022 respectively at three centers. Included patients were confirmed diagnoses of CAI through arthroscopy, as well as individuals who had undergone MRI and physical examinations that ruled out ligament injuries. DL models were constructed based on a multi-label paradigm. A transformer-based multi-label DL model (AnkleNet) was developed and compared with four convolution neural network (CNN) models. Subsequently, a reader study was conducted to evaluate the impact of model assistance on clinicians when diagnosing challenging cases: identifying rotational CAI (RCAI). Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS: Our transformer-based model achieved AUC of 0.910 and 0.892 for detecting lateral and medial collateral ligament injury, respectively, both of which was significantly higher than that of CNN-based models (all P < 0.001). In terms of further CAI diagnosis, it exhibited a macro-average AUC of 0.870 and a balanced accuracy of 0.805. The reader study indicated that incorporation with our model significantly enhanced the diagnostic accuracy of clinicians (P = 0.042), particularly junior clinicians, and led to a reduction in diagnostic variability. The code of the model can be accessed at https://github.com/ChiariRay/AnkleNet. CONCLUSION: Our transformer-based model was able to detect lateral and medial collateral ligament injuries based on MRI and outperformed CNN-based models, demonstrating a promising performance in diagnosing CAI, especially RCAI patients.

The PIEZO1/miR-155-5p/GDF6/SMAD2/3 signaling axis is involved in inducing the occurrence and progression of osteoarthritis under excessive mechanical stress.

OBJECTIVE: To elucidate the molecular mechanism of overloading-induced osteoarthritis (OA) and to find a novel therapeutic target. METHODS: We utilized human cartilage specimens, mouse chondrocytes, a destabilization of the medial meniscus (DMM) mouse model, and a mouse hindlimb weight-bearing model to validate the role of overloading on chondrocyte senescence and OA development. Then, we observed the effect of PIEZO1-miR-155-5p-GDF6-SMAD2/3 signaling axis on the preservation of joint metabolic homeostasis under overloading in vivo, in vitro and ex vivo by qPCR, Western blot, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, immunofluorescence, SA-ß-gal staining, CCK8 assay, et al. Finally, we verified the therapeutic effects of intra-articular injection of miR-155-5p inhibitor or recombinant GDF6 on the murine overloading-induced OA models. RESULTS: Chondrocytes sensesed the mechanical overloading through PIEZO1 and up-regulated miR-155-5p expression. MiR-155-5p mimics could copy the effects of overloading-induced chondrocyte senescence and OA. Additionally, miR-155-5p could suppress the mRNA expression of Gdf6-Smad2/3 in various tissues within the joint. Overloading could disrupt joint metabolic homeostasis by downregulating the expression of anabolism indicators and upregulating the expression of catabolism indicators in the chondrocytes and synoviocytes, while miR-155-5p inhibition or GDF6 supplementation could exert an antagonistic effect by preserving the joint homeostasis. Finally, in the in vivo overloading models, intra-articular injection of miR-155-5p inhibitor or recombinant GDF6 could significantly mitigate the severity of impending OA and lessened the progression of existing OA. CONCLUSION: GDF6 overexpression or miR-155-5p inhibition could attenuate overloading-induced chondrocyte senescence and OA through the PIEZO1-miR-155-5p-GDF6-SMAD2/3 signaling pathway. Our study provides a new therapeutic target for the treatment of overloading-induced OA.

Multifunctional Injectable Hydrogel Microparticles Loaded with miR-29a Abundant BMSCs Derived Exosomes Enhanced Bone Regeneration by Regulating Osteogenesis and Angiogenesis.

The study investigated whether both the osteogenic and angiogenic potential of Exos (Exosomes) can be enhanced by overexpression of exosomal miRNA (microRNA) and to confirm whether Exos loaded in HMPs (Hydrogel microparticles) exert long-term effects during new bone formation. BMSCs and Exos are successfully obtained. In vitro and in vivo experiments confirmed that HDAC4 (Histone deacetylase 4) is inhibited by miR-29a overexpression accompanied by the upregulation of RUNX2 (Runt-related transcription factor 2) and VEGF (Vascular Endothelial Growth Factor), thereby enhancing osteogenic and angiogenic capabilities. The HMP@Exo system is synthesized from HB-PEGDA (Hyperbranched Poly Ethylene Glycol Diacrylate)- and SH-HA (Sulfhydryl-Modified Hyaluronic Acid)-containing Exos using a microfluidic technique. The HMP surface is modified with RGD (Arg-Gly-Asp) peptides to enhance cell adhesion. The system demonstrated good injectability, remarkable compatibility, outstanding cell adhesion properties, and slow degradation capacity, and the sustained release of Agomir-29a-Exos (Exosomes derived from Agomir-29a transfected BMSCs) from HMPs enhanced the proliferation and migration of BMSCs and HUVECs (Human Umbilical Vein Endothelial Cells) while promoting osteogenesis and angiogenesis. Overall, the findings demonstrate that the HMP@Exo system can effectively maintain the activity and half-life of Exos, accompanied by overexpression of miR-29a (microRNA-29a). The injectable system provides an innovative approach for accelerating fracture healing by coupling osteogenesis and angiogenesis.

Expanding from unilateral to bilateral: A robust deep learning-based approach for predicting radiographic osteoarthritis progression.

OBJECTIVE: To develop and validate a deep learning (DL) model for predicting osteoarthritis (OA) progression based on bilateral knee joint views. METHODS: In this retrospective study, knee joints from bilateral posteroanterior knee radiographs of participants in the Osteoarthritis Initiative were analyzed. At baseline, participants were divided into testing set 1 and development set according to the different enrolled sites. The development set was further divided into a training set and a validation set in an 8:2 ratio for model development. At 48-month follow-up, eligible patients were formed testing set 2. The Bilateral Knee Neural Network (BikNet) was developed using bilateral views, with the knee to be predicted as the main view and the contralateral knee as the auxiliary view. DenseNet and ResNext were also trained and compared as the unilateral model. Two reader tests were conducted to evaluate the model's value in predicting incident OA. RESULTS: Totally 3583 participants were evaluated. The BikNet we proposed outperformed ResNext and DenseNet (all area under the curve [AUC] < 0.71, P < 0.001) with AUC values of 0.761 and 0.745 in testing sets 1 and 2, respectively. With assistance of the BikNet increased clinicians' sensitivity (from 28.1-63.2% to 42.1-68.4%) and specificity (from 57.4-83.4% to 64.1-87.5%) of incident OA prediction and improved inter-observer reliability. CONCLUSION: The DL model, constructed based on bilateral knee views, holds promise for enhancing the assessment of OA and demonstrates greater robustness during subsequent follow-up evaluations as compared with unilateral models. BikNet represents a potential tool or imaging biomarker for predicting OA progression.

Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis.

Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derived stem cells (ScASCs). However, it remains unclear which type of Exos offers superior therapeutic benefit for OA. This study first compared the differences between Exos derived from IPFP stem cells (ExosIPFP) and ScAT stem cells (ExosScAT) in OA treatment. Results suggested that ExosIPFP significantly inhibit the degradation of cartilage extracellular matrix (ECM) than ExosScAT, following this, the differences in microRNA (miRNA) expression between the two types of Exos using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen and over-expressed in ExosScAT (ExosScAT-99b-3p), both in vivo and in vitro experiments demonstrated its efficacy in inhibiting the expression of ADAMTS4, promoting the repair of the ECM in OA. Finally, microfluidic technology was performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) for encapsulating Exos (HMPs@exos), the injectability, sustained release of Exos and long-term therapeutic effect on OA were validated. In summary, these results suggest miR-99 b-3p regulates the degradation of cartilage ECM by targeting ADAMTS4, the upregulation of miR-99 b-3p in ExosScAT would enable them to exhibit comparable or even superior effectiveness to ExosIPFP for OA treatment, making it a promising approach for OA treatment. Considering the abundant resources of ScAT and the limited availability of IPFP, ScAT harvested through liposuction could be genetically engineered to yield Exos for OA treatment. Furthermore, the encapsulation of Exos in HMPs provides an injectable sustained local drug release system, which could potentially enhance the efficacy of Exos and hold potential as future therapeutic strategies.

Inhibition of LncRNA SNHG14 protects chondrocyte from injury in osteoarthritis via sponging miR-137.

Long-chain noncoding small nucleolar RNA host gene 14 (LncRNA SNHG14) is highly expressed in various diseases and promotes diseases progression, but the role and mechanism of LncRNA SNHG14 on targeting miR-137 in promoting osteoarthritis (OA) chondrocyte injury remains unclear. To measure the expression of the LncRNAs SNHG14 and miR-137, cell survival, inflammatory response, chondrocyte apoptosis, and extracellular matrix (ECM) levels, we subjected human chondrocytes to a variety of lipopolysaccharide (LPS) concentrations. To measure the luciferase activity of SNHG14-WT and SNHG14-MUT transfected with miR-137 mimic or miR-NC mimic, luciferase reporter genes were utilized. The results showed that chondrocyte viability was significantly inhibited with LPS treatment and chondrocyte inflammatory response, apoptosis and extracellular matrix degradation were significantly increased. However, the above results were significantly reversed after LncRNA SNHG14 inhibition. The luciferase activity bound to miR-137 was decreased in SNHG14-WT group, but there was no change in SNHG14-mut group, which indicated that LncRNA SNHG14 inhibited miR-137 expression as a miRNA sponge. In conclusion, inhibition of LncRNA SNHG14 attenuates chondrocyte inflammatory response, apoptosis and extracellular matrix degradation by targeting miR-137 in LPS induced chondrocytes.

Arthroscopic Direct Anterior-to-Posterior Suture Suspension Fixation for the Treatment of Posterior Cruciate Ligament Tibial Avulsion Fracture.

OBJECTIVES: A posterior cruciate ligament (PCL) avulsion fracture of the tibial attachment site is a specific type of PCL injury that is difficult and unpleasant to manage. The objective of this study is to report the preliminary results of a newly developed technique: arthroscopic endobutton-suture fixation using a single tibial tunnel. METHODS: From January 2016 to January 2018, 120 patients with PCL avulsion fracture who met our criteria were recruited. Sixty cases were treated by arthroscopic direct anterior-to-posterior suture suspension fixation (endobutton-suture group), and 60 cases were treated by arthroscopic screw-suture fixation (screw-suture group). All radiographic studies were recorded. The curative effect was evaluated by the range of motion (ROM), KT-2000, International Knee Documentation Committee (IKDC) scores, Tegner activity scale, and Lysholm scoring system. For statistical analysis the Student t-test was used. RESULTS: The average follow-up duration was 24 months. Findings and difficulties in surgery are the following. The lax anterior cruciate ligament is one of the diagnostic criteria. The anatomic location of PCL avulsion fractures is deep and surrounded by nerves and vessels; thus, operating through this region is difficult. After each tunnel drilling, the debris at the edge of opening needs to be cleaned to avoid obscuring the operator's vision or wearing the sutures. In endobutton-suture group, ROM improved from 0° preoperatively to 140.0° ± 5.6° at the last follow-up (P < 0.001). The postoperative KT-2000 arthrometric data at 90 N were available for all patients. The IKDC score was 23.6 ± 2.6 and 91.4 ± 4.1 pre- and postoperatively, respectively. The Tegner score improved from 1.2 ± 0.6 to 7.3 ± 2.3 (p < 0.001). The median Lysholm knee score increased from 40.4 ± 5.2 preoperatively to 90.1 ± 10.1 postoperatively (p < 0.001). The operative time was shorter in the endobutton-suture group (p < 0.001). The Lysholm knee score in the endobutton-suture group was lower than that in the endobutton-suture group (3.1 ± 1.2 vs. 4.2 ± 1.8, p < 0.01). No significant complications were noted in the study. CONCLUSIONS: The arthroscopic direct anterior-to-posterior suture suspension fixation is a simple and reliable method that not only provides better clinical outcomes, but also fixes avulsion fragments of any size.

Effects of Cartilage Progenitor Cells, Bone Marrow Mesenchymal Stem Cells and Chondrocytes on Cartilage Repair as Seed Cells: An in vitro Study.

Purpose: To determine the effects of cartilage progenitor cells, bone marrow mesenchymal stem cells and chondrocytes on cartilage repair as seed cells. Methods: Porcine cartilage progenitor cells (CPCs), bone marrow mesenchymal stem cells (BMSCs) and chondrocytes (CCs) were obtained from the femoropatellar joints of young pigs, and seeded in agarose gel as a graft. During the 28-day culture, proliferation ability was measured by MTT assay, and gene expression of Collagen I, Collagen II, Aggrecan and SOX 9 were measured by qPCR. Qualitative and quantitative analysis of collagen, glycosaminoglycan and DNA were appraised by immunohistochemical staining and biochemical assay, and integration strength was analyzed by push-out tests. Results: After 28-day culture, proliferation ability of CPCs and BMSCs was higher than CCs. Collagen, glycosaminoglycan, DNA content and chondrocyte-related genes expression in the cartilage progenitor cells seeded gel were significantly higher than the other two gels. Integration strength in the cartilage progenitor cells seeded gel was also higher compared with the other two gels. Conclusion: Compared with CCs and BMSCs, CPCs in vitro have dominance in the ability of cell proliferation and differentiation as seed cells in tissue engineering.

APKASS Consensus Statement on Chronic Syndesmosis Injury, Part 1: Clinical Manifestation, Radiologic Examination, Diagnosis Criteria, Classification, and Nonoperative Treatment.

BACKGROUND: Clinical manifestation, radiologic examination, diagnostic criteria, classification, and nonoperative treatment strategies regarding chronic syndesmosis injury remain unclear. PURPOSE: An international group of experts representing the fields of sports injuries in the foot and ankle area were invited to collaboratively advance toward consensus opinions based on the best available evidence regarding chronic syndesmosis injuries. All were members of the Asia-Pacific Knee, Arthroscopy and Sports Medicine Society (APKASS). STUDY DESIGN: Consensus statement. METHODS: From November to December 2020, a total of 111 international experts on sports medicine or ankle surgery participated in a 2-stage Delphi process that included an anonymous online survey and an online meeting. A total of 13 items with 38 statements were drafted by 13 core authors. Of these, 4 items with 15 clinical questions and statements were related to the clinical manifestation, radiologic examination, diagnostic criteria, classification, and nonoperative treatment strategies for chronic syndesmosis injury and are presented here. Each statement was individually presented and discussed, followed by a general vote. The strength of consensus was characterized as follows: consensus, 51% to 74%; strong consensus, 75% to 99%; unanimous, 100%. RESULTS: Of the 15 questions and statements, 5 reached unanimous support and 10 achieved strong consensus. CONCLUSION: This APKASS consensus statement, developed by international experts in the field, will assist surgeons and physical therapists with diagnosis, classification, and nonoperative treatment strategies for chronic syndesmosis injury.

APKASS Consensus Statement on Chronic Syndesmosis Injury, Part 3: Fusion Techniques, Comorbidity Treatments, Postoperative Rehabilitation, and Return-to-Sport Indications.

BACKGROUND: Questions regarding surgical fusion techniques, postoperative treatment, and indications for return to sport after chronic syndesmosis injury or its comorbidities remain unanswered. PURPOSE: An international group of experts representing the field of injuries in the foot and ankle area was invited to collaboratively advance toward consensus opinions based on the best available evidence regarding chronic syndesmosis injury. All were members of the Asia-Pacific Knee, Arthroscopy and Sports Medicine Society (APKASS). STUDY DESIGN: Consensus statement. METHODS: From November to December 2020, a total of 111 international experts on sports medicine or ankle surgery participated in a 2-stage Delphi process that included an anonymous online survey and an online meeting. A total of 13 items with 38 statements were drafted by 13 core authors. Of these, 4 items with 6 clinical questions and statements were related to surgical fusion techniques, comorbidity treatments, postoperative rehabilitation, and return-to-sports indications and are presented here. Each statement was individually presented and discussed, followed by a general vote. The strength of consensus was characterized as follows: consensus, 51% to 74%; strong consensus, 75% to 99%; and unanimous, 100%. RESULTS: Of the 6 questions and statements, 5 achieved unanimous support and 1 reached strong consensus. CONCLUSION: This APKASS consensus statement, developed by international experts in the field, will assist surgeons and physical therapists with surgical and postoperative treatment strategies for chronic syndesmosis injury.

APKASS Consensus Statement on Chronic Syndesmosis Injury, Part 2: Indications for Surgical Treatment, Arthroscopic or Open Debridement, and Reconstruction Techniques of Suture Button and Screw Fixation.

BACKGROUND: The indications for surgical treatment of chronic syndesmosis injury are challenging for many orthopaedic clinicians, as there is no international consensus on the optimal management of these injuries. PURPOSE: An international group of experts representing the field of sports injuries in the foot and ankle area was invited to collaboratively advance toward consensus opinions based on the best available evidence regarding chronic syndesmosis injury. All were members of the Asia-Pacific Knee, Arthroscopy and Sports Medicine Society (APKASS). STUDY DESIGN: Consensus statement. METHODS: From November to December 2020, a total of 111 international experts on sports medicine or ankle surgery participated in a 2-stage Delphi process that included an anonymous online survey and an online meeting. A total of 13 items with 38 statements were drafted by 13 core authors. Of these, 9 items with 17 clinical questions and statements were related to indications for surgical treatment, arthroscopic versus open debridement, and suture button versus screw fixation reconstruction techniques and are presented here. Each statement was individually presented and discussed, followed by a general vote. The strength of consensus was characterized as follows: consensus, 51% to 74%; strong consensus, 75% to 99%; and unanimous, 100%. RESULTS: Of the 17 questions and statements, 4 achieved unanimous support, 11 reached strong consensus, and 2 reached consensus. CONCLUSION: This APKASS consensus statement, developed by international experts in the field, will assist surgeons and physical therapists with surgical indications and techniques for chronic syndesmosis injury.

High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis.

OBJECTIVES: The aim of this study was to detect levels of common lipid species in serum and synovial fluid (SF) of primary knee osteoarthritis (OA) patients and investigate their correlations with disease severity. MATERIALS AND METHODS: The study enrolled 184 OA patients receiving arthroscopic debridement or total knee arthroplasty and 180 healthy controls between April 2012 and March 2018. Total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) levels were analyzed in serum and SF of OA patients, and in serum of healthy individuals. The Noyes rating criteria, Kellgren-Lawrence (KL) grading system, and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores were, respectively, used to assess cartilage damage, radiographic severity, and symptomatic severity of OA. RESULTS: No significant differences were found in serum TG and ApoB levels between the 2 groups, while OA patients had higher TC and LDL-C levels and lower HDL-C and ApoA1 levels (P < 0.05). Pearson correlation analysis revealed SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage scores, KL grades as well as WOMAC scores (P < 0.05), which were still significant after adjusting for confounding factors (P < 0.05). Receiver operating characteristic curve analysis revealed SF HDL-C (area under the curve [AUC]: 0.816) and ApoA1 (AUC: 0.793) were also good predictors of advanced-stage OA (P < 0.001). CONCLUSION: SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage, radiographic severity, and symptomatic severity of primary knee OA, emerging as potential biomarkers for radiographic advanced-stage OA, which may serve as predictors of disease severity.

Endoscopic reconstruction for chronic Achilles tendon ruptures using a hamstring tendon autograft.

BACKGROUND: To determine the safety and efficacy of endoscopic reconstruction of chronic Achilles tendon ruptures using a hamstring tendon autograft at mid-term follow-up. METHODS: We reviewed the medical records of patients with chronic Achilles tendon rupture treated surgically by endoscopic reconstruction using a hamstring tendon autograft at our institution between March 2010 and October 2015. Radiologic outcomes were assessed using pre- and postoperative magnetic resonance imaging (MRI). Functional outcomes were evaluated with the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, the Plantar Flexion Strength (PFS), the Victorian Institute of Sport Assessment-Achilles (VISA-A) scale, the Visual Analogue Scale (VAS) pain score, and the Arner-Lindholm standard. All patients achieved primary healing with no lengthening of the Achilles tendon, skin necrosis, infection, deep vein thrombosis or other complications. RESULTS: Mean follow-up period was 15 ± 3 months (range, 12-18 months). There was no Achilles tendon re-rupture. MRI examination revealed that Achilles tendon continuity was restored. Patients' mean AOFAS, PFS, and VISA-A scores were significantly higher and mean VAS pain score was significantly lower after surgery compared to before (P < 0.05). According to Arner-Lindholm standards, there were twenty (76.9%) excellent, six (23.1%) good, and zero bad outcomes. CONCLUSION: Endoscopic reconstruction utilizing a hamstring tendon autograft is a safe and efficacious option for repair of chronic Achilles tendon ruptures. Studies with larger sample sizes and a longer follow-up are required to confirm the advantage of this technique compared to open surgery.

A modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction: medium-term clinical and radiologic results comparable with open reconstruction.

BACKGROUND: The aim of this study was to compare clinical and radiologic outcomes of a modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction with traditional open reconstruction. METHODS: From January 2012 and March 2016, 60 eligible patients with chronic lateral ankle instability (CLAI) received all arthroscopic remnant-preserving reconstruction or open reconstruction of the anterior talofibular ligament and calcaneofibular ligament using semitendinosus autograft. They were divided into the arthroscopic group (n = 28) and the open group (n = 32). The American Orthopaedic Foot and Ankle Society (AOFAS),visual analog scale (VAS), and Karlsson scores and ankle range of motion (ROM) were used to evaluate clinical outcomes pre-operatively and at six and 12 months and the final follow-up of at least 24 months post-operatively, with SF-36 physical component summary (PCS) and mental component summary (MCS) scores evaluated for quality of life, and the anterior talar translation and talar tilt measurements for radiologic outcomes. RESULTS: There was no difference in pre-operative demographics between two groups (P > 0.05). At the final follow-up, the AOFAS, VAS, Karlsson, SF-36 PCS, and MCS scores improved significantly in both groups (P < 0.05). However, no significant difference was found in AOFAS (91.9 ± 6.8 vs 91.1 ± 5.5), VAS (2.7 ± 1.7 vs 2.5 ± 1.6), Karlsson (95.3 ± 6.7 vs 94.8 ± 6.5), SF-36 PCS (53.2 ± 6.1 vs 52.9 ± 5.7), and MCS scores (55.7 ± 5.8 vs 54.2 ± 5.4) between the two groups (P > 0.05). There was no significant difference in post-operative operated/non-operated ankle ROM between two groups (P > 0.05). No significant difference was observed in talar tilt angle (7.6 ± 4.1° vs 6.8 ± 3.6°) and anterior talar translation (5.8 ± 1.7 mm vs 5.7 ± 1.5 mm) between the two groups at the final follow-up (P > 0.05), although these two variables improved significantly in both groups (P < 0.05). No severe complications were encountered in both groups during the follow-up period. CONCLUSIONS: The modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction could produce excellent clinical and radiologic outcomes comparable with open reconstruction.

Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition).

In recent years, as living standards have continued to improve, the number of diabetes patients in China, along with the incidence of complications associated with the disease, has been increasing. Among these complications, diabetic foot disease is one of the main causes of disability and death in diabetic patients. Due to the differences in economy, culture, religion and level of medical care available across different regions, preventive and treatment methods and curative results for diabetic foot vary greatly. In multidisciplinary models built around diabetic foot, the timely assessment and diagnosis of wounds and appropriate methods of prevention and treatment with internal and external surgery are key to clinical practice for this pathology. In 2019, under the leadership of the Jiangsu Medical Association and Chinese Diabetes Society, the writing group for the Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition) was established with the participation of scholars from the specialist areas of endocrinology, burn injury, vascular surgery, orthopedics, foot and ankle surgery and cardiology. Drawing lessons from diabetic foot guidelines from other countries, this guide analyses clinical practices for diabetic foot, queries the theoretical basis and grades and gives recommendations based on the characteristics of the pathology in China. This paper begins with assessments and diagnoses of diabetic foot, then describes treatments for diabetic foot in detail, and ends with protections for high-risk feet and the prevention of ulcers. This manuscript covers the disciplines of internal medicine, surgical, nursing and rehabilitation and describes a total of 50 recommendations that we hope will provide procedures and protocols for clinicians dealing with diabetic foot.

[Clinical analysis of autogenous tendon reconstruction under total arthroscopy in treatment of chronic Achilles tendon rupture].

OBJECTIVE: To investigate the effectiveness of autogenous tendon reconstruction under total arthroscopy in the treatment of chronic Achilles tendon rupture. METHODS: Between June 2015 and June 2018, 16 patients with chronic Achilles tendon ruptures were treated by autogenous tendon reconstruction under total arthroscopy. Of the 16 patients, 11 were males and 5 were females. Their mean age was 40.7 years (range, 21-55 years). The disease duration was 14-20 months (mean, 16.4 months). Preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score was 41.2±2.2 and the pain visual analogue scale (VAS) score was 7.9±1.2. MRI and B-ultrasonography examinations showed that the Achilles tendon was not continuous. The length of Achilles tendon defect was 5.0-10.3 cm, with an average of 5.8 cm. The rupture of the Achilles tendon happened on top of the insertion of the tendon in 4 cases and at the tendon-muscle belly connection in 12 cases. The operation time, intraoperative blood loss, hospital stay, and related complications were recorded. The AOFAS score and VAS score were used to evaluate the improvement of ankle joint function and pain. RESULTS: The average operation time was 77.2 minutes (range, 60-90 minutes). The average intraoperative blood loss was 20.5 mL (range, 15-30 mL). The average hospital stay was 7.2 days (range, 5-10 days). All incisions healed by first intention. There was no skin necrosis, infection, or deep vein thrombosis. All the patients were followed up 8-18 months, with an average of 12 months; and 10 cases were followed up more than 12 months. During the follow-up, there was no Achilles tendon re-rupture, and the symptoms of pain and heel lifting failure significantly improved. MRI reexamination showed that the continuity of Achilles tendon recovered. At 1, 3, 6, and 12 months postoperatively, AOFAS scores significantly improved and VAS scores significantly reduced, except for 1 month postoperatively, the scores at other time points were superior to that before operation, the differences were significant ( P<0.05). CONCLUSION: Autogenous tendon reconstruction under total arthroscopy in the treatment of chronic Achilles tendon rupture has the advantages of small trauma, rapid functional recovery, and satisfactory surgical efficacy.

Eliminating senescent chondrogenic progenitor cells enhances chondrogenesis under intermittent hydrostatic pressure for the treatment of OA.

BACKGROUND: Osteoarthritis (OA) is a major cause of limb dysfunction, and distraction arthroplasty which generates intermittent hydrostatic pressure (IHP) is an effective approach for OA treatment. However, the result was not always satisfactory and the reasons remained unresolved. Because aging is recognized as an important risk factor for OA and chondrogenic progenitor cells (CPCs) could acquire senescent phenotype, we made a hypothesis that CPCs senescence could have harmful effect on chondrogenesis and the outcome of distraction arthroplasty could be improved by eliminating senescent CPCs pharmacologically. METHODS: The role of senescent CPCs on distraction arthroplasty was first determined by comparing the cartilage samples from the failure and non-failure patients. Next, the biological behaviors of senescent CPCs were observed in the in vitro cell culture and IHP model. Finally, the beneficial effect of senescent CPCs clearance by senolytic dasatinib and quercetin (DQ) on cartilage regeneration was observed in the in vitro and in vivo IHP model. RESULTS: Larger quantities of senescent CPCs along with increased IL-1 ß secretion were demonstrated in the failure patients of distraction arthroplasty. Senescent CPCs revealed impaired proliferation and chondrogenic capability and also had increased IL-1 ß synthesis, typical of senescence-associated secretory phenotype (SASP). CPCs senescence and SASP formation were mutually dependent in vitro. Greater amounts of senescent CPCs were negatively correlated with IHP-induced chondrogenesis. In contrast, chondrogenesis could be significantly improved by DQ pretreatment which selectively induced senescent CPCs into apoptosis in the in vitro and in vivo IHP model. Mechanistically, senescent CPCs elimination could decrease SASP formation and therefore promote the proliferation and chondrogenic regeneration capacity of the surrounding survived CPCs under IHP stimulation. CONCLUSIONS: Eliminating senescent CPCs by senolytics could decrease SASP formation and improve the result of joint distraction arthroplasty effectively. Our study provided a novel CPCs senescence-based therapeutic target for improving the outcome of OA treatment.

AKT3 deficiency in M2 macrophages impairs cutaneous wound healing by disrupting tissue remodeling.

AKT signaling and M2 macrophage-guided tissue repair are key factors in cutaneous wound healing. A delay in this process threatens human health worldwide. However, the role of AKT3 in delayed cutaneous wound healing is largely unknown. In this study, histological staining and transcriptomics demonstrated that prolonged tissue remodeling delayed wound healing. This delay was accompanied by defects in AKT3, collagen alpha-1(I) chain (COL1A1), and collagen alpha-1(XI) chain (COL11A1) expression and AKT signaling. The defect in AKT3 expression was M2 macrophage-specific, and decreased AKT3 protein levels were observed in CD68/CD206-positive macrophages from delayed wound tissue. Downregulation of AKT3 in M2 macrophages did not influence cell polarization but impaired collagen organization by inhibiting COL1A1 and COL11A1 expression in human skin fibroblasts (HSFs). Moreover, a co-culture model revealed that the downregulation of AKT3 in the human monocytic cell line (THP-1)-derived M2 macrophages impaired HSF proliferation and migration. Finally, cutaneous wound healing in AKT3-/- mice was much slower than that of AKT3+/+ mice, and F4/80 macrophages from the AKT3-/- mice had an impaired ability to promote wound healing. Thus, the downregulation of AKT3 in M2 macrophages prolonged tissue remodeling and delayed cutaneous wound healing.

[Differential expression of transient receptor potential vanilloid receptor 4 protein in osteoarthritis and normal cartilages].

OBJECTIVE: To investigate the differential expression of transient receptor potential vanilloid receptor 4 (TRPV4) protein in the osteoarthritis (OA) and normal cartilages, and explore the role of TRPV4 in the prevention and treatment of OA. METHODS: The cartilage tissues from the patients of knee OA (OA group) and femoral neck fracture (control group) were taken. In OA group, there were 6 males and 9 females; the age ranged from 55 to 78 years (mean, 69 years); the Kellgren-Lawrence (K-L) score was 3.0±0.8. In control group, there were 5 males and 10 females; the age ranged from 57 to 91 years (mean, 71 years). There was no significant difference in gender and age between the two groups ( P>0.05). Western blot, real-time fluorescence quantitative PCR, Masson staining, and immunohistochemical staining were used to detect the difference in protein and mRNA expressions of TRPV4 between the OA and normal cartilages. Then the relationship between the K-L score of OA and the rate of TRPV4-positive cells was analyzed. RESULTS: The relative expression of TRPV4 protein and mRNA in OA group were 0.454±0.199 and 2.951±1.200, which were higher than those in control group (0.165±0.074, 1.437±0.682). The difference in relative expression of TRPV4 protein was significant ( t=2.718, P=0.026). Histology observation showed that the chondrocytes arranged disorderly in OA group, the structure of extracellular matrix was abnormal, and the cartilage defect reached the deep layer. There were more TRPV4-positive cells in the degenerated tissue, and the rate of TRPV4-positive cells was 37.353%±13.496%. The chondrocytes were arranged well in control group, and the rate of TRPV4-positive cells was only 9.642%±3.284%. There was a significant difference between the two groups ( t=7.491, P=0.000). The rate of TRPV4-positive cells in OA group was positively correlated with the OA K-L score ( r=0.775, P=0.001). CONCLUSION: The TRPV4 expression increased in OA cartilages that may contribute to the development of OA.