One-Stage Arthroscopic Multiple Ligament Reconstruction for Schenck IV Knee Dislocation.

PURPOSE: Schenck IV knee dislocation patients have dissatisfactory knee function and return-to-sport rate with the existing treatment methods. The purpose of this study was to illustrate a one-stage arthroscopic multiple ligament reconstruction method for treating Schenck IV knee dislocations. METHODS: A retrospective case series study was performed. All patients with a history of Schenck IV knee dislocation who underwent one-stage arthroscopic multi-ligament reconstruction from 2010 to 2018 were followed for 24 months. The outcomes, including general patient data, Lysholm scores, International Knee Documentation Committee (IKDC) scores, visual analog scale (VAS) pain scores, knee active range of motion, and complications, were reviewed. The data was analyzed with paired-samples t-test. RESULTS: A total of 12 patients, comprising nine males and three females, were followed up and reviewed. The mean age at the time of the surgical procedure was 40.3 ± 9.0 (22-57) years. The mean body mass index (BMI) was 24.6 ± 4.9 (15.2-32.5) kg/m2 . The mean IKDC score and Lysholm score before surgery were 30.4 ± 6.1 (21-42) and 28.2 ± 6.2 (22-39), respectively. The average operation time was 121.8 minutes. The mean IKDC score and Lysholm score at the 24-month follow-up were 80.6 ± 6.5 (68-92) and 82.0 ± 7.5 (72-95), respectively. There were significant differences in the IKDC and Lysholm scores between the preoperative and 24-month postoperative time points (p < 0.01). The mean knee range of motion was 124.6° ± 6.6° (115°-135°) at the 24-month follow-up. No major complications occurred. CONCLUSIONS: The results of this retrospective study suggest that the new arthroscopic one-stage multi-ligament reconstruction technique is an effective way to treat Schenck IV knee dislocation with satisfactory postoperative knee function.

Reconstruction of Bony Defects after Tumor Resection with 3D-Printed Anatomically Conforming Pelvic Prostheses through a Novel Treatment Strategy.

There has been an increasing interest and enormous applications in three-dimensional (3D) printing technology and its prosthesis, driving many orthopaedic surgeons to solve the difficult problem of bony defects and explore new ways in surgery approach. However, the most urgent problem is without an effective prosthesis and standard treatment strategy. In order to resolve these problems, this study was performed to explore the use of a 3D-printed anatomically conforming pelvic prosthesis for bony defect reconstruction following tumor resection and to describe a detailed treatment flowchart and the selection of a surgical approach. Six patients aged 48-69 years who had undergone pelvic tumor resection underwent reconstruction using 3D-printed anatomically conforming pelvic prostheses according to individualized bony defects between March 2016 and June 2018. According to the Enneking and Dunham classification, two patients with region I+II tumor involvement underwent reconstruction using the pubic tubercle-anterior superior iliac spine approach and the lateral auxiliary approach and one patient with region II+III and three patients with region I+II+III tumor involvement underwent reconstruction using the pubic tubercle-posterior superior iliac spine approach. The diagnoses were chondrosarcoma and massive osteolysis. After a mean follow-up duration of 30.33 ± 9.89 months (range, 18-42), all patients were alive, without evidence of local recurrence or distant metastases. The average blood loss and blood transfusion volumes during surgery were 2500.00 ± 1461.51 ml (range, 1200-5000) and 2220.00 ± 1277.62 ml (range, 800-4080), respectively. During follow-up, the mean visual analogue scale (VAS) score decreased, and the mean Harris hip score increased. There were no signs of hip dislocation, prosthetic loosening, delayed wound healing, or periprosthetic infection. This preliminary study suggests the clinical effectiveness of 3D-printed anatomically conforming pelvic prostheses to reconstruct bony defects and provide anatomical support for pelvic organs. A new surgical approach that can be used to expose and facilitate the installation of 3D-printed prostheses and a new treatment strategy are presented. Further studies with a longer follow-up duration and larger sample size are needed to confirm these encouraging results.

MiR-92a inhibits fibroblast-like synoviocyte proliferation and migration in rheumatoid arthritis by targeting AKT2.

Growing data have indicated that the miR-17-92 cluster is implicated in inflammatory response and rheumatoid arthritis (RA). This study was aimed to investigate the effects of miR-92a on the proliferation and migration of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Our results showed that miR-92a was significantly down-regulated in RA synovial tissue and RA-FLSs, whereas the protein level of AKT2 is increased. Restoration of miR-92a suppressed the proliferation and migration of RA-FLSs. Down-regulation of miR-92a promotes proliferation and migration of normal human FLSs. Dual luciferase reporter gene assay showed that miR-92a could specifically bind with the 30UTR of AKT2 and significantly repressed the luciferase activity. Down-regulation or up-regulation of miR-92a significantly increased or decreased the protein and phosphorylation levels of AKT2. siRNA-mediated down-regulation of AKT2 significantly prevented cell proliferation and migration of RA-FLSs, which were similar to the effects induced by overexpression of miR-92a. Moreover, AKT2 overexpression rescued miR-92a-mediated suppressive effect on proliferation and migration of RA-FLS. Thus, miR-92a could inhibit the proliferation and migration of RA-FLSs through regulation of AKT2 expression.

TNF­α increases inflammatory factor expression in synovial fibroblasts through the toll­like receptor­3­mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis.

Osteoarthritis is a type of joint disease that may lead to other joint diseases. Previous research has demonstrated that tumor necrosis factor (TNF)­α is associated with osteoarthritis activity and pathology. The possible mechanisms of the TNF­α­mediated signaling pathway have not been clearly elaborated in synovial fibroblasts. The present study aimed to investigate the potential mechanisms of TNF­α in a mouse model of iodoacetate­induced osteoarthritis. Reverse transcription­quantitative polymerase chain reaction, ELISA, western blotting and immunohistochemistry were performed to evaluate the role of TNF­α in the progression of osteoarthritis. The results revealed that the serum levels of TNF­α, interleukin (IL)­1ß, IL­4 and IL­6 were significantly upregulated in a mouse model of iodoacetate­induced osteoarthritis compared with healthy mice (P<0.01). TNF­α, IL­1ß, IL­4 and IL­6 mRNA and protein levels were also significantly upregulated in synovial fibroblasts in the experimental mice (P<0.01). It was demonstrated that TNF­α increased pro­inflammation factors matrix metalloproteinase (MMP)­3, MMP­9, nuclear factor (NF)­κB and receptor activator of NF­κB ligand (RANKL) in synovial fibroblasts. It was also observed that the toll­like receptor (TLR)­3 was significantly upregulated and extracellular signal­regulated kinase (ERK) and protein kinase B (AKT) were significantly downregulated in synovial fibroblasts in osteoarthritis mice (P<0.01). An in vitro assay demonstrated that TNF­α inhibitor decreased mRNA and protein levels of IL­1ß, IL­4 and IL­6 in synovial fibroblasts. The knockdown of TLR­3 abolished the TNF­α upregulated mRNA and protein levels of IL­1ß, IL­4 and IL­6 in synovial fibroblasts. In addition, the knockdown of TLR­3 also reversed TNF­α­upregulated ERK and AKT expression in synovial fibroblasts. In vivo assays demonstrated that TNF­α inhibitor significantly decreased the deposition of IL­1ß, IL­4 and IL­6 as well as bone destruction and significantly increased the body weight and osteoarthritis score for osteoarthritic mice (P<0.01). TNF­α inhibitor decreased TLR­3 and significantly increased the expression and phosphorylation of ERK and AKT in articular cartilage (P<0.01). In conclusion the results of the present study indicate that TNF­α serves an essential role in synovial fibroblasts in osteoarthritis, suggesting that inhibition of TNF­α may decrease inflammation via the TLR­3­mediated ERK/AKT signaling pathway in a mouse model of monosodium iodoacetate­induced osteoarthritis.

Overexpressed miR-145 inhibits osteoclastogenesis in RANKL-induced bone marrow-derived macrophages and ovariectomized mice by regulation of Smad3.

BACKGROUND: MicroRNAs (miRs) play an important role in osteoclastogenesis. However, no study has investigated the underlying molecular mechanisms of miR-145 in this process. The purpose of the present study was to investigate the role of miR-145 and its post-transcriptional mechanism in the progression of osteoclast differentiation. METHODS: Macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL) were used to induce osteoclastogenesis originated from bone marrow-derived macrophages (BMMs). Female C57BL/6J mice were divided into sham, OVX, OVX + NC-agomir and OVX + miR-145-agomir groups. Tartrate-resistant acid phosphatase (TRAP) staining was performed to identify osteoclasts in-vitro and in-vivo. The mRNA and protein levels in osteoclast and tibia were assayed by qRT-PCR and western blotting, respectively. RESULTS: miR-145 expression was inhibited in RANKL-induced osteoclastogenesis, whereas overexpression of miR-145 attenuated it. We further found that Smad3 is a direct target gene of miR-145 by binding with its 3'-UTR. Overexpression of miR-145 significantly suppressed Smad3 mRNA and protein expression. In-vivo, miR-145 agomir treatment inhibited osteoclast activity in OVX mice by inhibiting Smad3 expression. CONCLUSION: We provide the evidence that over-expression of miR-145 could inhibit osteoclast differentiation, at least partially, by decreasing Smad3 expression.

Circular RNA expression profiles in synovial fluid: a promising new class of diagnostic biomarkers for osteoarthritis.

BACKGROUND: Previous studies suggest that circRNAs abnormally function in the progression of osteoarthritis (OA). However, little is known about the diagnostic value of circRNAs in patients with OA. To assess potential applications of circRNAs as diagnostic tools in OA, expression profiles of circRNAs in synovial fluid from OA patients and healthy subjects were obtained. METHODS: Microarray analysis was performed to profile the expression of circRNAs in an unbiased manner. CircRNA expression in synovial fluid was identified by real-time quantitative polymerase chain reaction (RT-qPCR). The diagnostic value was evaluated using receiver operating characteristics (ROC) curves and the area under the ROC curves (AUC). Spearman correlation analysis was performed to assess the correlation of circRNAs and clinical parameters. RESULTS: We identified five circRNAs that were significantly elevated in synovial fluid from OA patients compared with those of the healthy controls. Among these five circRNAs, hsa_circ_0104873, hsa_circ_0104595, and hsa_circ_0101251 could effectively separate patients with OA from healthy controls with high AUC (0.683, 0.708 and 0.754, respectively). Furthermore, we found that three circRNAs were positively correlated with the degree of radiographic grading and symptomatic severity of OA patients. CONCLUSION: This study suggests that increased expression of hsa_circ_0104873, hsa_circ_0104595, and hsa_circ_0101251 in synovial fluid from OA patients may serve as potential biomarkers for OA screening.

EWS/FLI-l peptide-pulsed dendritic cells induces the antitumor immunity in a murine Ewing's sarcoma cell model.

An increasing number of T-cell epitopes derived from various tumor-associated antigens have been reported, and they proved to play significant roles for tumor rejection both in vivo and in vitro. Over 85% of Ewing's sarcoma family of tumors (ESFTs) express tumor-specific chimeric protein EWS/FLI-1, making it an attractive target for therapeutic cytotoxic T-lymphocyte responses. Here, we identified a novel peptide epitope derived from the EWS/FLI-1 protein and demonstrated that effectors induced by the peptide could specifically secrete IFN-γ and lyse the tumor cell line of EWS/FLI-1-positive and HLA-matched cells. In addition, mice treated with dendritic cells pulsed with the EWS/FLI-1 epitope were able to reject a lethal tumor inoculation of the Ewing's sarcoma A673 cells. Therefore, these data provide evidence for the use of the EWS/FLI-l peptide epitope in T cell-based immunotherapeutic concepts against Ewing's sarcoma cell in vitro and in vivo.

[Case-control studies on double bundle posterior cruciate ligament reconstruction with remnant fiber preservation].

OBJECTIVE: To study the clinical efficacy of double bundle posterior cruciate ligament (PCL) reconstruction with remnant preservation. METHODS: From January 2007 to November 2011, 50 patients with PCL rupture met the inclusion criteria were divided into two groups: remnant preservation group (RP group) and remnant resection group (RR group). There were 19 males and 7 females in the RP group, ranging in age from 18 to 55 years, with a mean of (32.250 +/- 11.085) years old. The duration from injury to operation ranged from 2 to 66 months, with an average of (17.481 +/- 3.568) months. Among the RR group, 17 patients were male and 7 patients were female, ranging in age from 20 to 54 years old, with an average of (31.458 +/- 9.569) years. The duration from injury to operation ranged from 3 to 72 months, with a mean of (19.354 +/- 3.950) months. The patients in both groups suffered from instability of knee joint, got a positive result of posterior drawer test. In the RP group, the intercondylar notch remnant fiber, scar tissue and synovial were preserved in operation, only the free ligament in the intercondylar notch was resected. In the RR group, the remnant fiber, scar tissue and synovial tissue of adhesive parts were resected. In both groups, autologous semitendinosus and gracilis tendon double-bundle PCL reconstruction were carried out, the tibia was fixed with an absorbable interference screw with post-tie fixation, and the femur side was compositely fixed with absorbable interference screws and suspending fixation. Each patient received both subjective assessment (IKDC subjective evaluation, Lysholm scoring and Cincinnati rating) and objective clinical assessment (IKDC objective evaluation and Kneelax 3 tibia backward measurement) before operation and two years after operation. RESULTS: IKDC subjective evaluation: 92.167 +/- 4.177 in the RP group,which was higher than 87.542 +/- 5.687 in the RR group (P = 0.010). Lysholm scores: 90.917 +/- 4.413 in the RP group, which was higher than 87.083 +/- 5.149 in the RR group (P = 0.027). Cincinnati knee scores: 92.125 +/- 4.003 in the RP group, which was higher than 87.791 +/- 6.665 in the RR group (P = 0.027). IKDC objective evaluation:no significant statistical differences between RP group and RR group. Kneelax 3 assessment : tibia backward test with Kneelax 3 under 132 N showed no significant statistical difference between RP group and RR group, which were (3.958 +/- 0.693) mm and (4.029 +/- 0.846) mm respectively (P = 0.795). CONCLUSION: The study shows a significant advantage of remnant fiber preservation than remnant fiber resection in double-bundle PCL construction in terms of subjective knee function recovery after operation. There is no significant difference in postoperative knee stability.

Dendritic cells transfected with PD-L1 recombinant adenovirus induces T cell suppression and long-term acceptance of allograft transplantation.

The purpose of this study is to assess the potential of dendritic cells transfected with PD-L1 recombinant adenovirus induces CD8+ T cell suppression and kidney allograft tolerance. To prove it, DCs transfected with PD-L1 recombinant adenovirus (DC/Ad-PD-L1) were transferred into the MHC-mismatched rat kidney transplants. After kidney transplantation, the mixed lymphocyte reaction (MLR) assay and kidney function were analyzed. The results demonstrated that after administration of DC/Ad-PD-L1, the proliferation, cytokines secretion and activation marker expression of CD8+ T cells were suppressed. In addition, DC/Ad-PD-L1 could improve kidney function and survival of transplants. The findings suggested that DC/Ad-PD-L1 could induce CD8+ T cell tolerance and lead to kidney allograft tolerance, which provided a promising finding for clinical application.

[Importance of early diagnosis and operative treatment for trans-scaphoid perilunate dislocation].

OBJECTIVE: To evaluate the effectiveness of open reduction and internal fixation and repair of palmar ligment in treating trans-scaphoid perilunate dislocation. METHODS: From June 1995 to June 2001,14 patients with trans-scaphoid perilunate dislocation were treated with open reduction and internal fixation and repair of palmar ligment. Among them,there were 13 males and 1 female,the ranging in age from 21 to 38 years,averaged 25.4 years. All patients were posterior dislocation and all operations were performed within 2 weeks after injury. RESULTS: All patients were followed up from 24 to 60 months with an average of 28.3 months. Thirteen scaphoid fractures were primary healed and functions of wrist joint were good. Bone disunion was found in 1 case and part functions of wrist joint were limited. No found necrosis of lunate and scaphoid. According to clinical scoring system of Cooney, 9 case got excellent results, 3 good, 1 fair and 1 poor. CONCLUSION: Open reduction and internal fixation and repair of palmar ligament is effective in treating trans-scaphoid perilunate dislocation,which can early provide steady fixation for scaphoid,and profit to recover blood supply of lunatum and subterminal scaphoid.

[Treatment of chronic Achilles tendon rupture by use of allogeneic tendon].

OBJECTIVE: To evaluate the clinical result of allogeneic tendon in treatment of chronic Achilles tendon rupture. METHODS: From July 1996 to November 2000, 6 cases of chronic Achilles tendon rupture were treated by use of allogeneic flexor tendon to repair Achilles tendon with Bosworth way. Five cases were followed up 27-53 months with an average of 38.5 months. RESULTS: According to Arner-Lindholm criteria for curative result, the result was excellent in 1 case and good in 4 cases. CONCLUSION: Allogeneic tendon in repair of chronic Achilles tendon is effective. It can avoid the injury and complication caused by autograft.