Complex phase behavior of dihydroxyl-functionalized ionic liquids at low temperature.

Here, we have synthesized six dihydroxyl-functionalized ionic liquids for phase behavior studies at low temperature via crystallographic methods, Raman spectroscopy, differential scanning calorimetry (DSC), and density functional theory (DFT) calculations. Phase varieties are observed depending on the direction and strength of hydrogen bonding. Our studies also show that the ILs could be potentially excellent phase-change thermal storage materials with nearly no change of the phase transition enthalpy.

Modified Suture-Button Latarjet Procedure With Coracoacromial Ligament and Pectoralis Minor Preservation Achieves Good Clinical Outcomes at 2-Year Follow-Up: Case Series of Latarjet Technique.

PURPOSE: To evaluate whether the modified suture-button Latarjet procedure with coracoacromial ligament (CAL) and pectoralis minor (PM) preservation could achieve excellent outcomes at the 2-year follow-up. METHODS: During January 2019 to January 2021, the data of patients who underwent modified suture-button Latarjet with CAL and PM preservation in our department were collected. The glenoid bone loss of these patients was greater than 20% or greater than 10% with high demands for exercise. Partial coracoid osteotomy was based on the results of a preoperative 3-dimensional computed tomography evaluation of the glenoid defect area and corresponding coracoid process morphology. The preoperative and postoperative clinical results were assessed. The minimal clinically important difference (MCID) was used to compare improvement in clinical outcomes. Graft-glenoid union and remodeling were assessed using postoperative 3-dimensional computed tomography, and magnetic resonance imaging was performed to confirm the integrity of the CAL and PM postoperatively. RESULTS: In total, 35 patients were included in this study; the mean follow-up time was 26.9 ± 1.9 months. No case of recurrent dislocation or sublaxity. Significant improvements were observed in mean visual analog scale (VAS) scores for pain during motion, American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and Walch-Duplay score (P < .001). The percentage of patients achieving at least an MCID improvement in clinical outcomes was VAS 85.71%, ASES 97.14%, Rowe 100%, and Walch-Duplay 97.14%. Thirty-three patients (94.3% of all cases) were able to return to their preoperative sport levels, 34 grafts (97.1%) achieved bone union (1 soft union) in 6.3 ± 2.2 months, and the coracoid grafts restored 97.1 ± 4.0% of the perfect-fitting circle at the last follow-up. Postoperative computed tomography scan showed that 31 grafts (88.6%) were placed ideally in vertical view. In the axial view, 25 grafts (82.9%) were flushed to the glenoid, whereas 1 and 5 grafts were fixed medially and laterally, respectively. The CAL and PM were visualized postoperatively. No arthropathy was observed in any patient at the last follow-up. CONCLUSIONS: The modified suture-button Latarjet procedure with CAL and PM preservation obtained good clinical and radiological results without recurrence or complications. A substantial number of patients (>85%) achieved the MCID for the VAS, ASES, Rowe, and Walch-Duplay scores. In addition, the malpositioned graft (17.1%) did not cause arthropathy of the joints at 2-year follow-up. LEVEL OF EVIDENCE: Level IV, retrospective case series.

NEAT1/miR-181c Regulates Osteopontin (OPN)-Mediated Synoviocyte Proliferation in Osteoarthritis.

Osteoarthritis (OA) is characterized by progressive destruction of articular cartilage, resulting in significant disability. Inflammatory cytokines commonly initiate the extreme changes in the synovium and cartilage microenvironment of the OA patients, subsequently resulting in cell dysfunctions, especially synoviocyte dysfunction. We revealed that the expression of osteopontin (OPN), which has been reported to regulate expression of various inflammatory factors associating with the pathogenesis of OA including matrix metalloprotease 13 (MMP13), interlukine-6 and 8 (IL-6 and IL-8), is significantly upregulated in OA tissues. In the present study, online tools were used to screen out the candidate miRNAs of OPN. Among the candidate miRNAs, miR-181c inhibited OPN mRNA expression the most strongly. Ectopic expression of miR-181c significantly repressed synoviocyte proliferation, as well as the levels of OPN, MMP13, IL-6, and IL-8. Further, the candidate lncRNAs of miR-181c were screened out by using DianaTools; among which NEAT1 showed to inversely regulate miR-181c. By performing Luciferase assays, we revealed that NEAT1 competed with OPN for miR-181c binding. After NEAT1 knockdown, MMP13, IL-6, and IL-8 expression was reduced; the synoviocyte proliferation was repressed, as well as OPN protein levels; the suppressive effect of NETA1 knockdown on synoviocyte proliferation and the indicated factors were partially reversed by miR-181c inhibition. In OA tissues, OPN mRNA, and NEAT1 expression was upregulated, whereas miR-181c expression was downregulated, indicating that targeting NEAT1 to rescue miR-181c expression so as to inhibit OPN expression and synoviocyte proliferation might be an efficient strategy for OA treatment. J. Cell. Biochem. 118: 3775-3784, 2017. © 2017 Wiley Periodicals, Inc.

[Mid-term effectiveness of LU-tarjet procedure for recurrent anterior shoulder dislocation].

Objective: To evaluate the mid-term effectiveness of limited unique coracoid osteotomy suture button fixation Latarjet (LU-tarjet) procedure in treatment of recurrent anterior shoulder dislocation. Methods: Between March 2017 and February 2019, 56 patients with recurrent shoulder dislocation were treated with arthroscopic LU-tarjet procedure. There were 44 males and 12 females with an average age of 26.3 years (range, 18-41 years). Shoulder joint dislocation occurred 2-16 times, with an average of 7.5 times. The time from the initial dislocation to operation ranged from 6 months to 13 years, with a median of 4.6 years. Preoperative shoulder joint fear test and re-reduction test were positive in all patients. The Beighton score of joint relaxation ranged from 1 to 7, with an average of 4.1. The shoulder Instability Severity Index Score (ISIS) ranged from 5 to 10, with an average of 7.8. The size of glenoid defects on the affected side ranged from 15% to 32% (mean, 22.4%). All patients had Hill-Sachs injuries of varying degrees. Six patients had re-dislocation after Bankart surgery. The operation time, incision healing, and postoperative complications were recorded. The range of motion (shoulder flexion, extension, abduction, external rotation, 90° external rotation, and internal rotation) and muscle strength in shoulder flexion, abduction, external rotation, and internal rotation) of shoulder joint were compared between pre- and post-operation. The improvement of shoulder function was evaluated using the American Association for Shoulder and Elbow Surgery (ASES) score, Walch-Duplay score, and Rowe score. X-ray films and three-dimensional CT were used to analyze the location, healing, and remolding of bone graft, the repair of glenoid defect, and degenerative changes of the shoulder joint. Results: All operations were successfully completed. The operation time ranged from 42 to 98 minutes, with an average of 63 minutes. All incisions healed by first intention. All patients were followed up 5-7 years (mean, 6.3 years). During follow-up, 2 patients experienced shoulder subluxation within 1 year after operation and 1 patient experienced recurrent shoulder joint pain. The remaining patients had no related complications. At last follow-up, there was no significant difference between the two groups ( P>0.05) in range of motion (shoulder flexion, extension, abduction, external rotation, 90° external rotation, and internal rotation) and muscle strength in shoulder flexion, abduction, external rotation, and internal rotation). The ASES score, Rowe score, and Walch-Duplay score of shoulder significantly improved when compared with those before operation ( P<0.05). Postoperative CT showed that 53 cases (94.64%) of coracoid bone masses were centered placed vertically, 2 cases (3.57%) were superior, and 1 case (1.79%) was inferior; 49 cases (87.50%) of the coracoid bone grafts were flush with the glenoid, 2 cases (3.57%) and 5 cases (8.93%) were medially and laterally positioned. The volume of coracoid bone graft decreased first and then increased, and the shape of the bone graft was continuously remodeling and gradually matched with the track of the humerus head (the optimal circle of the glenoid), all coracoid bone grafts healed. At last follow-up, the coverage rate of optimal glenoid circle was 89.6%-100%, with an average of 97.4%. The area of glenoid defect was 2.6%±1.3%, which significantly decreased when compared with preoperative (22.4%±5.4%) ( P<0.05). At last follow-up, no obvious degenerative changes of shoulder joint was observed. Conclusion: LU-tarjet procedure for recurrent anterior shoulder dislocation has good mid-term effectiveness with short operation time and few complications.

Purified exosome product enhances chondrocyte survival and regeneration by modulating inflammation and promoting chondrogenesis.

Aim: This study was to detect the effects of purified exosome product (PEP) on C28/I2 cells and chondrocytes derived from osteoarthritis patients. Materials & methods: Cell viability and apoptosis assays were used to detect the effect of PEP on cells. qRT-PCR and cell fluorescence assays were used to investigate the potential mechanism of PEP on cell chondrogenesis. Results: PEP was internalized by cells at a fast rate and enhanced cellular proliferation and migration while attenuating apoptosis. These findings reflect the fact that PEP can increase the expression of PCNA and reduce the expression of CASP3/7/9 and BAX. Conclusion: This study suggests an innovative strategy for chondrogenesis that could be applied to osteoarthritis repair in the future.

Enhancing Functional Recovery after Segmental Nerve Defect Using Nerve Allograft Treated with Plasma-Derived Exosome.

BACKGROUND: Nerve injuries can result in detrimental functional outcomes. Currently, autologous nerve graft offers the best outcome for segmental peripheral nerve injury. Allografts are alternatives, but do not have comparable results. This study evaluated whether plasma-derived exosome can improve nerve regeneration and functional recovery when combined with decellularized nerve allografts. METHODS: The effect of exosomes on Schwann cell proliferation and migration were evaluated. A rat model of sciatic nerve repair was used to evaluate the effect on nerve regeneration and functional recovery. A fibrin sealant was used as the scaffold for exosome. Eighty-four Lewis rats were divided into autograft, allograft, and allograft with exosome groups. Gene expression of nerve regeneration factors was analyzed on postoperative day 7. At 12 and 16 weeks, rats were subjected to maximum isometric tetanic force and compound muscle action potential. Nerve specimens were then analyzed by means of histology and immunohistochemistry. RESULTS: Exosomes were readily taken up by Schwann cells that resulted in improved Schwann cell viability and migration. The treated allograft group had functional recovery (compound muscle action potential, isometric tetanic force) comparable to that of the autograft group. Similar results were observed in gene expression analysis of nerve regenerating factors. Histologic analysis showed no statistically significant differences between treated allograft and autograft groups in terms of axonal density, fascicular area, and myelin sheath thickness. CONCLUSIONS: Plasma-derived exosome treatment of decellularized nerve allograft may provide comparable clinical outcomes to that of an autograft. This can be a promising strategy in the future as an alternative for segmental peripheral nerve repair. CLINICAL RELEVANCE STATEMENT: Off-the-shelf exosomes may improve recovery in nerve allografts.

LUtarjet-limit unique coracoid osteotomy Latarjet (With video).

Background: The Latarjet procedure is an effective technique for the treatment of recurrent anterior shoulder dislocation with glenoid bone loss. However, the inevitable destruction of the coracoacromial arch may result in humeral head translation. The aim of the study is to introduce a modified Latarjet technique with coracoacromial arch preservation as well as its short term clinical outcomes. Methods: We propose a novel individualized flexible arthroscopic suture button fixation Latarjet technique called `LUtarjet' with video. Precise measurements of the coracoid process, glenoid deficiency and osteotomy plane were made preoperatively. Only three arthroscopic portals were needed and limit unique coracoid osteotomy was performed with coracoacromial arch preservation. The mini window splitting of the subscapularis was performed from the posterior to the anterior direction and the split window was as small as 8-10 mm in length. Results: A total of 27 patients (25.6 ± 5.4 years) were included in the study. The average surgical duration was 55.6 ± 6.3 min and the mean follow-up time was 8.1 ± 1.5 months. The functional score was significantly improved at the last follow-up. Radiologic evidence showed that the bone graft healing was placed in the desired position. No complications were found. Conclusions: We present a fast, easy, accurate, safe arthroscopic 'LUtarjet' technique called FEAST that can simplify the arthroscopic Latarjet process and achieve a satisfactory bone graft position and satisfactory short-term clinical outcomes. Level of evidence: IV, case series.

Total shoulder arthroplasty versus reverse total shoulder arthroplasty: Outcome comparison in osteoarthritis patients with or without concurrent rotator cuff deficiency.

Osteoarthritis (OA) is a common shoulder disorder that impacts shoulder functions. Shoulder arthroplasty is often required to restore function and quality of life. Reverse total shoulder arthroplasty (RSA), which was originally designed mainly for irreparable rotator cuff damage, has gained popularity in recent years for the treatment of advanced shoulder OA instead of the clinically standard total shoulder arthroplasty (TSA). However, this RSA has some nonnegligible flaws such as higher complications rate and economic cost, not mention the following problems caused by irreversible physical structural damage. Therefore, the employment of RSA needs to be carefully considered. This study aimed to compare TSA and RSA in OA patients with or without rotator cuff damage to better guide clinical decision making. We believe the radical use of RSA in patients without rotator cuff deficiency may cause more harm than good. We queried the Nationwide Inpatient Sample (NIS) database from 2011 to 2014 to collect information on OA patients who received TSA and RSA. Patients were divided into 2 groups of comparison according to the presence of rotator cuff deficiency and matched with propensity score analysis. A total of 57,156 shoulder arthroplasties were identified. RSA patients in the rotator cuff deficiency group had significant higher transfusion rates and longer hospital stays. RSA patients without rotator cuff deficiency had a statistically significantly higher number of implant-related mechanical complications, acute upper respiratory infections and postoperative pain. Overall, RSA incurred higher costs in both groups. For OA patients with rotator cuff deficiencies, RSA has its benefits as complication rates were comparable to TSA. For those patients without rotator cuff deficiencies, the use of RSA should be reconsidered as there were more complications with higher severity.

Age-related cellular and microstructural changes in the rotator cuff enthesis.

Rotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age-related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age-related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased nonmineralized zone. Proliferation, migration, and colony-forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and highlights the importance of using age-appropriate models, as well as provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.

Expression and prognosis analyses of BUB1, BUB1B and BUB3 in human sarcoma.

Budding Uninhibited By Benzimidazoles are a group of genes encoding proteins that play central roles in spindle checkpoint during mitosis. Improper mitosis may lead to aneuploidy which is found in many types of tumors. As a key mediator in mitosis, the dysregulated expression of BUBs has been proven to be highly associated with various malignancies, such as leukemia, gastric cancer, breast cancer, and liver cancer. However, bioinformatic analysis has not been applied to explore the role of the BUBs in sarcomas. Herein, we investigate the transcriptional and survival data of BUBs in patients with sarcomas using Oncomine, Gene Expression Profiling Interactive Analysis, Cancer Cell Line Encyclopedia, Kaplan-Meier Plotter, LinkedOmics, and the Database for Annotation, Visualization and Integrated Discovery. We found that the expression levels of BUB1, BUB1B and BUB3 were higher in sarcoma samples and cell lines than in normal controls. Survival analysis revealed that the higher expression levels of BUB1, BUB1B and BUB3 were associated with lower overall and disease-free survival in patients with sarcomas. This study implies that BUB1, BUB1B and BUB3 are potential treatment targets for patients with sarcomas and are new biomarkers for the prognosis of sarcomas.

A biomechanical comparison of a mesh suture to a polyblend suture in a porcine tendon model.

BACKGROUND: The suture-tendon interface turned out to be the weak point of a repaired rotator cuff. A double rip-stop (DRS) technique was developed to enhance the strength of the suture-tendon interface. The first aim of this study was to compare the suture-tendon interface strength between mesh suture and the No. 2 FiberWire (FW), which is commonly used in the clinic. The second aim was to compare the biomechanical properties of rotator cuff repair between mesh suture and No. 2 FiberWire using a typical suture-bridge (SB) and DRS techniques. METHODS: Eighteen porcine subscapularis tendon (SST) was randomly assigned to the Mesh-tendon group and FiberWire-tendon group. A single suture loop was passed through the SST with a Mesh suture or FiberWire. Thirty-two infraspinatus tendons (ISTs) were randomly assigned to four groups: SB-Mesh group: SB technique with Mesh suture, SB-FW group: SB technique with FiberWire, DRS-Mesh group: DRS technique with Mesh suture, and DRS-FW group: DRS technique with FiberWire. All repaired specimens were underwent failure testing. Failure modes, load to create a 3-mm gap, failure load, and stiffness were compared. RESULTS: There were no significant differences between the Mesh-tendon group and FiberWire-tendon group regarding the failure load, stiffness, and ultimate stress. When the same technique was used, the rotator cuff repaired with a mesh suture had the similar load to create a 3-mm gap, failure load, and stiffness compared with FiberWire. When the same suture was used, the DRS technique had a significantly higher load to create a 3-mm gap formation and failure load compared with the SB technique. CONCLUSIONS: The repair failure strength and stiffness using the mesh suture were similar to the FiberWire suture regardless of the repair techniques. However, the repair strength in the DRS technique was significantly stronger than the SB technique when the same suture material was used.

Circ_0134111 knockdown relieves IL-1ß-induced apoptosis, inflammation and extracellular matrix degradation in human chondrocytes through the circ_0134111-miR-515-5p-SOCS1 network.

BACKGROUND: Osteoarthritis (OA) is characterized by chondrocyte injury and dysfunction, such as excessive apoptosis, inflammatory response and extracellular matrix (ECM) degradation. Circular RNA (circRNA) deregulation is reported to be involved in OA. Our study aimed to explore the role of circ_0134111 in OA. METHODS: Human chondrocytes were treated with interleukin-1ß (IL-1ß) to mimic OA cell model. The expression of circ_0134111, miR-515-5p and suppressor of cytokine signaling 1 (SOCS1) mRNA was measured by real-time quantitative polymerase chain reaction (RT-qPCR), and the protein levels of SOCS1 and apoptosis-/inflammation-/ECM-related markers were determined by western blot. Cell proliferation and cell apoptosis were assessed using cell counting kit-8 (CCK-8) and flow cytometry assay, respectively. For mechanism analysis, the predicted interaction between miR-515-5p and circ_0134111 or SOCS1 was verified by dual-luciferase reporter assay, pull-down assay and RNA immunoprecipitation (RIP) assay. Rescue experiments were performed to explore the interplay between miR-515-5p and circ_0134111 or SOCS1. RESULTS: Circ_0134111 was overexpressed in OA cartilage tissues and IL-1ß-induced chondrocytes. IL-1ß-induced chondrocyte apoptosis, inflammatory responses and ECM degradation were alleviated by circ_0134111 knockdown or miR-515-5p restoration. Circ_0134111 acted as miR-515-5p sponge to regulate miR-515-5p expression, and miR-515-5p deficiency reversed the effects of circ_0134111 knockdown in IL-1ß-induced chondrocytes. MiR-515-5p directly bound to SOCS1, and circ_0134111 decoyed miR-515-5p to increase SOCS1 level. MiR-515-5p restoration alleviated IL-1ß-induced chondrocyte apoptosis, inflammatory responses and ECM degradation, While SOCS1 overexpression partly abolished these effects. CONCLUSION: Circ_0134111 knockdown alleviated apoptosis, inflammatory responses and ECM degradation in OA cell model by mediating the miR-515-5p-SOCS1 network, hinting that circ_0134111 was involved in OA progression.

Targeting nerve growth factor, a new option for treatment of osteoarthritis: a network meta-analysis of comparative efficacy and safety with traditional drugs.

OBJECTIVE: Osteoarthritis (OA) is the most common joint disease and leading cause of pain and disability in the elderly population. Most guidelines recommend the use of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids for the non-operative treatment of OA. Monoclonal nerve growth factor (NGF) antibodies are new drugs with the potential to provide pain relief and functional improvement in OA. We compared the efficacy (pain reduction and functional improvement), and safety of monoclonal NGF antibodies with NSAIDs and opioids in the treatment of OA with a Bayesian network meta-analysis. RESULTS: 38 articles, comprising 41 trials and 20489 patients with OA were included. Overall from the network meta-analysis, anti-NGFs were the most effective drugs for pain relief (Standardized Mean Difference or SMD compared with placebo 4.25, 95% CI 2.87 to 5.63, Surface Under the Cumulative RAnking curve or SUCRA=93.7%) and for functional improvement (SMD 4.90, 95% CI 3.46 to 6.33, SUCRA=98.3%). Although anti-NGFs were associated with higher risk of peripheral sensation abnormality (paresthesia and pruritus), they were not associated with higher risk of other AEs (headaches and nausea) or with higher withdrawal rates related to AEs. CONCLUSIONS: Monoclonal NGF antibodies provide significantly greater pain relief and functional improvement in OA compared to NSAIDs and opioids. Monoclonal NGF antibodies are not associated with severe AEs. More studies are needed to confirm these findings. METHODS: PubMed, CNKI, Web of Science, Scopus, Embase and Cochrane Library databases were searched for relevant studies (OA treated with anti-NGFs, opioids, selective COX-2 inhibitors or NSAIDs) published between January 1999 to January 2020. Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement and AEs were assessed.

Biomechanical Comparison of Augmentation of Engineered Tendon-Fibrocartilage-Bone Composite With Acellular Dermal Graft Using Double Rip-Stop Technique for Canine Rotator Cuff Repair.

BACKGROUND: The retear rate after rotator cuff repair remains unacceptably high. Various biological engineered scaffolds have been proposed to reduce the retear rate. We have developed a double rip-stop repair with medial row knot (DRSK) technique to enhance suture-tendon strength and a novel engineered tendon-fibrocartilage-bone composite (TFBC) for rotator cuff repair. HYPOTHESIS: DRSK rotator cuff repair augmented with TFBC will have better biomechanical properties than that of DRSK repair with an acellular dermal graft (DG). STUDY DESIGN: Controlled laboratory study. METHODS: Fresh-frozen canine shoulders (n = 30) and knees (n = 10) were used. TFBCs were harvested from the patellar tendon-tibia complex and prepared for rotator cuff repair. The infraspinatus tendon was sharply detached from its bony attachment and randomly assigned to the (1) control group: DRSK repair alone, (2) TFBC group: DRSK repair with TFBC, and (3) DG group: DRSK repair with DG. All specimens were tested to failure, and videos were recorded. The footprint area, tendon thickness, load to create 3-mm gap formation, failure load, failure modes, and stiffness were recorded and compared. Data were recorded as mean ± SD. RESULTS: The mean load to create a 3-mm gap in both the control group (206.8 ± 55.7 N) and TFBC group (208.9 ± 39.1 N) was significantly higher than that in the DG group (157.7 ± 52.3 N) (P < .05 for all). The failure load of the control group (275.7 ± 75.0 N) and TFBC group (275.2 ± 52.5 N) was significantly higher compared with the DG group (201.5 ± 49.7 N) (P < .05 for both comparisons). The stiffness of the control group (26.4 ± 4.7 N/mm) was significantly higher than of the TFBC group (20.4 ± 4.4 N/mm) and the DG group (21.1 ± 4.8 N/mm) (P < .05 for both comparisons). CONCLUSION: TFBC augmentation showed superior biomechanical performance to DG augmentation in rotator cuff tears repaired using the DRSK technique, while there was no difference between the TFBC and control groups. CLINICAL RELEVANCE: TFBC may help to reduce retear or gap formation after rotator cuff repair using the DRSK technique.

Is Lutikizumab, an Anti-Interleukin-1α/ß Dual Variable Domain Immunoglobulin, efficacious for Osteoarthritis? Results from a bayesian network meta-analysis.

OBJECTIVE: Most guidelines recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol for the nonoperative treatment of osteoarthritis (OA), but the use of them is limited by the tolerability and safety concerns. Lutikizumab is a novel anti-IL-1α/ß dual variable domain immunoglobulin that can simultaneously bind and inhibit IL-1α and IL-1ß to relieve the pain and dysfunction symptoms. We conducted this network meta-analysis to comprehensively compare the clinical efficacy and safety of lutikizumab with other drugs recommended by guidelines. METHODS: We conducted a Bayesian network and conventional meta-analyses to compare the efficacy and safety of lutikizumab with other traditional drugs. All eligible randomized clinical trials, in PubMed, CNKI, EMBASE, and Web of Science databases, from January 2000 to January 2020, were included. The Cochrane risk of the bias assessment tool was used for quality assessment. Pain relief, function improvement, and risk of adverse effects (AEs) were compared in this study. RESULTS: 24 articles with 11858 patients were included. Duloxetine (DUL) had the largest effect for pain relief (4.76, 95% CI [2.35 to 7.17]), and selective cox-2 inhibitors (SCI) were the most efficacious treatment for physical function improvement (SMD 3.94, 95% CI [2.48 to 5.40]). Lutikizumab showed no benefit compared with placebo for both pain relief (SMD 1.11, 95% CI [-2.29 to 4.52]) and function improvement (SMD 0.992, 95% CI [-0.433 to 4.25]). Lutikizumab and all other drugs are of favorable tolerance for patients in the treatment of OA compared with placebo. CONCLUSIONS: Lutikizumab, the new anti-Interleukin-1α/ß dual variable domain immunoglobulin, showed no improvement in pain or function when compared with placebo. Selective cox-2 inhibitors and duloxetine remain the most effective and safest treatment for OA. More high-quality trials are still needed to reconfirm the findings of this study.

Biomechanical evaluation of a novel double rip-stop technique with medial row knots for rotator cuff repair: an in vitro study.

AIMS: Many biomechanical studies have shown that the weakest biomechanical point of a rotator cuff repair is the suture-tendon interface at the medial row. We developed a novel double rip-stop (DRS) technique to enhance the strength at the medial row for rotator cuff repair. The objective of this study was to evaluate the biomechanical properties of the DRS technique with the conventional suture-bridge (SB) technique and to evaluate the biomechanical performance of the DRS technique with medial row knots. METHODS: A total of 24 fresh-frozen porcine shoulders were used. The infraspinatus tendons were sharply dissected and randomly repaired by one of three techniques: SB repair (SB group), DRS repair (DRS group), and DRS with medial row knots repair (DRSK group). Specimens were tested to failure. In addition, 3 mm gap formation was measured and ultimate failure load, stiffness, and failure modes were recorded. RESULTS: The mean load to create a 3 mm gap formation in the DRSK and DRS groups was significantly higher than in the SB group. The DRSK group had the highest load to failure with a mean ultimate failure load of 395.0 N (SD 56.8) compared to the SB and DRS groups, which recorded 147.1 N (SD 34.3) and 285.9 N (SD 89.8), respectively (p < 0.001 for both). The DRS group showed a significantly higher mean failure load than the SB group (p = 0.006). Both the DRS and DRSK groups showed significantly higher mean stiffness than the SB group. CONCLUSION: The biomechanical properties of the DRS technique were significantly improved compared to the SB technique. The DRS technique with medial row knots showed superior biomechanical performance than the DRS technique alone.

MicroRNA-15a-5p Regulates the Development of Osteoarthritis by Targeting PTHrP in Chondrocytes.

BACKGROUND AND AIMS: A growing body of research has demonstrated that the degeneration of chondrocytes is the primary cause of osteoarthritis (OA). Parathyroid hormone-related protein (PTHrP) can alleviate the degeneration of chondrocytes via promotion of chondrocyte proliferation and inhibition of terminal differentiation, but the underlying mechanism remains unknown. This study aimed to identify the microRNAs (miRNAs) that may target PTHrP and regulate the proliferation and terminal differentiation of chondrocytes. METHODS: Bioinformatic analysis was used to predict which miRNAs target PTHrP. We collected human knee cartilage specimens to acquire the primary chondrocytes, which we then used to test the expression and function of the targeted miRNAs. To explore the effects of miR-15a-5p on the putative binding sites, specific mimics or inhibitors were transfected into the chondrocytes. Furthermore, a dual-luciferase reporter gene assay and chondrocyte degeneration-related factors were used to verify the possible mechanism. RESULTS: The expression of PTHrP was upregulated in the OA chondrocytes, whilst miR-15a-5p was downregulated in the OA chondrocytes. A negative correlation was observed between PTHrP and miR-15a-5p. The knockdown of miR-15a-5p promoted the growth of chondrocytes and inhibited calcium deposition, whilst overexpression of miR-15a-5p reversed this trend. The effect of miR-15a-5p overexpression was neutralised by PTHrP. Dual-luciferase reporter assays revealed that PTHrP can be used as a novel targeting molecule for miR-15a-5p. CONCLUSIONS: miR-15a-5p promotes the degeneration of chondrocytes by targeting PTHrP and, in addition to helping us understand the development of OA, may be a potential biomarker of OA.