Cardiac CIP protein regulates dystrophic cardiomyopathy.

Heart failure is a leading cause of fatality in Duchenne muscular dystrophy (DMD) patients. Previously, we discovered that cardiac and skeletal-muscle-enriched CIP proteins play important roles in cardiac function. Here, we report that CIP, a striated muscle-specific protein, participates in the regulation of dystrophic cardiomyopathy. Using a mouse model of human DMD, we found that deletion of CIP leads to dilated cardiomyopathy and heart failure in young, non-syndromic mdx mice. Conversely, transgenic overexpression of CIP reduces pathological dystrophic cardiomyopathy in old, syndromic mdx mice. Genome-wide transcriptome analyses reveal that molecular pathways involving fibrogenesis and oxidative stress are affected in CIP-mediated dystrophic cardiomyopathy. Mechanistically, we found that CIP interacts with dystrophin and calcineurin (CnA) to suppress the CnA-Nuclear Factor of Activated T cells (NFAT) pathway, which results in decreased expression of Nox4, a key component of the oxidative stress pathway. Overexpression of Nox4 accelerates the development of dystrophic cardiomyopathy in mdx mice. Our study indicates CIP is a modifier of dystrophic cardiomyopathy and a potential therapeutic target for this devastating disease.

Regulation of myonuclear positioning and muscle function by the skeletal muscle-specific CIP protein.

The appropriate arrangement of myonuclei within skeletal muscle myofibers is of critical importance for normal muscle function, and improper myonuclear localization has been linked to a variety of skeletal muscle diseases, such as centronuclear myopathy and muscular dystrophies. However, the molecules that govern myonuclear positioning remain elusive. Here, we report that skeletal muscle-specific CIP (sk-CIP) is a regulator of nuclear positioning. Genetic deletion of sk-CIP in mice results in misalignment of myonuclei along the myofibers and at specialized structures such as neuromuscular junctions (NMJs) and myotendinous junctions (MTJs) in vivo, impairing myonuclear positioning after muscle regeneration, leading to severe muscle dystrophy in mdx mice, a mouse model of Duchenne muscular dystrophy. sk-CIP is localized to the centrosome in myoblasts and relocates to the outer nuclear envelope in myotubes upon differentiation. Mechanistically, we found that sk-CIP interacts with the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex and the centriole Microtubule Organizing Center (MTOC) proteins to coordinately modulate myonuclear positioning and alignment. These findings indicate that sk-CIP may function as a muscle-specific anchoring protein to regulate nuclear position in multinucleated muscle cells.

Outcomes of early versus late functional weight-bearing after the acute Achilles tendon rupture repair with minimally invasive surgery: a randomized controlled trial.

INTRODUCTION: Optimal postoperative rehabilitation regimen for acute Achilles tendon rupture (AATR) remains unclear. It is important to evaluate whether early functional weight-bearing rehabilitation program after minimally invasive repair results in an earlier return to pre-injury activity but increases the risk of re-rupture. MATERIALS AND METHODS: This was a prospective randomized controlled trial involving 68 AATR patients undergoing minimally invasive surgery. 34 patients were enrolled in early weight­bearing mobilization accelerated rehabilitation group (AR group); 34 patients were enrolled in the traditional rehabilitation (TR) group. Outcomes measures included American Orthopaedic Foot and Ankle Society Score (AOFAS) score and Achilles Tendon Total Rupture Score (ATRS) score before surgery and 3, 6, and 12 months after surgery, incidence rate of Achilles tendon re-rupture and total complications, length of hospital stay, time return to work and sports. RESULTS: There was no significant difference in preoperative basic data between the two groups. However, AOFAS score and ATRS score were better in AR group than TR group at 3 months postoperatively (92.4 ± 3.5 vs 88.3 ± 4.5, P < 0.01; 91.1 ± 4.4 vs 88.9 ± 3.4, P = 0.03, respectively), the mean length of hospital stay (4.7 ± 1.5 vs 7.6 ± 2.0 days, P < 0.01) and time return to work (4.5 ± 1.0 vs 7.5 ± 1.6 weeks, P < 0.01) were shorter in AR group than in TR group. No statistical significance was calculated in patient-reported outcomes during the rest of the follow-up time and complications. CONCLUSION: Early accelerated rehabilitation with weight-bearing in patients with AATR after minimally invasive surgery results in better early functional outcomes and shows similar security and feasibility. REGISTRATION NO: ChiCTR2100043398.

LRTM1 promotes the differentiation of myoblast cells by negatively regulating the FGFR1 signaling pathway.

The proliferation and differentiation of myoblast cells are regulated by the fibroblast growth factor receptor (FGFR) signaling pathway. Although the regulation of FGFR signaling cascades has been widely investigated, the inhibitory mechanism that particularly function in skeletal muscle myogenesis remains obscure. In this study, we determined that LRTM1, an inhibitory regulator of the FGFR signaling pathway, negatively modulates the activation of ERK and promotes the differentiation of myoblast cells. LRTM1 is dynamically expressed during myoblast differentiation and skeletal muscle regeneration after injury. In mouse myoblast C2C12 cells, knockout (KO) of Lrtm1 significantly prevents the differentiation of myoblast cells; this effect is associated with the reduction of MyoD transcriptional activity and the overactivation of ERK kinase. Notably, further studies demonstrated that LRTM1 associates with p52Shc and inhibits the recruitment of p52Shc to FGFR1. Taken together, our findings identify a novel negative regulator of FGFR1, which plays an important role in regulating the differentiation of myoblast cells.

Clinical Characteristics and Prognosis of Osteoclast-like Giant Cell Tumors of the Pancreas Compared with Pancreatic Adenocarcinomas: A Population-Based Study.

BACKGROUND The incidence of osteoclast-like giant cell tumor of the pancreas (OGTP) is very low, and relatively little OGTP clinical data is available. The present study, therefore, sought to conduct a more comprehensive analysis of the clinical characteristics and prognosis of OGTP. MATERIAL AND METHODS A large population-based cohort analysis was conducted using the Surveillance, Epidemiology and End Results (SEER) registry. We conducted a systematic assessment of the demographic and clinical characteristics of these patients, in addition to assessing available prognostic and therapeutic data corresponding to their disease. We further compared overall survival (OS) in these OGTP and pancreatic adenocarcinoma (PA) patient cohorts, adjusting for sex, grade, stage, and surgical treatment by propensity score matching (PSM). RESULTS We included a total of 47 OGTP patients and 73 150 PA patients in the present analysis. The mean ages of PA and OGTP diagnosis were 68.0 and 62.8 years, respectively. Compared with PA patients, OGTP patients were more likely to be female (70.2% versus 48.7%, P<0.01), to have early-stage disease, to have lower rates of lymph node metastasis (17.0% versus 28.8%, P<0.01) and distant metastasis (17.0% versus 45.1%, P<0.01), and to have higher rates of tumor resection (70.2% versus 15.4%, P<0.01). OGTP patients also had a significantly longer median OS than did PA patients (13 months versus 6 months; hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.37-0.57, P<0.0001). No significant differences in tumor site preferences were detected. Our findings also suggested that being female, having early-stage disease, and undergoing surgical resection may be associated with a more favorable prognosis in patients with OGTP. CONCLUSIONS OGTP patients had distinctive clinical characteristics and a better prognosis compared with PA patients. Understanding these differences will help clinicians accurately recognize these diseases. Radical resection was beneficial to the survival of OGTP patients.

Total hip arthroplasty for Crowe type IV developmental dysplasia of the hip combined with intertrochanteric fracture: a case report and literature review.

BACKGROUND: Total hip arthroplasty for Crowe type IV developmental dysplasia of the hip (DDH) is a complex procedure. Crowe type IV DDH combined with intertrochanteric frature is very rare. CASE PRESENTATION: A 75-year-old patient suffering from left hip pain after a fall was sent to our hospital. Plain radiographs and computed tomography scans were used to diagnose this patient with DDH combined with an intertrochanteric fracture. We conducted a total hip arthroplasty using an S-rom prosthesis following subtrochanteric shortening osteotomy in this patient, after which steel wires were used to fix the intertrochanteric fracture. The patient did not suffer any significant intraoperative or postoperative complications, and treatment was sufficient to overcome lower leg abnormalities. The patient was encouraged to resume walking with support at 3 days post-surgery, and at 6-month postoperatively he had regained the majority of his original range of motion. At 10-month postoperatively, the intertrochanteric fracture and subtrochanteric osteotomy of left femur had healed effectively,and the patient's VAS and mHSS scores had improved significantly. CONCLUSIONS: Total hip arthroplasty is an effective approach to treat patients suffering from Crowe type IV DDH combined with an intertrochanteric fracture, and can achieve satisfactory clinical outcomes.

Relationship between inflammation and progression of an abdominal aortic aneurysm in a rabbit model based on 18F-FDG PET/CT imaging.

OBJECTIVE: To explore the relationship between abdominal aortic aneurysm development and inflammation in the rabbit through the establishment of a rabbit infrarenal abdominal aortic aneurysm model and the use of 18F-FDG PET/CT imaging. METHODS: Twenty male New Zealand rabbits were administered an elastase intracavity perfusion to induce an infrarenal abdominal aortic aneurysm model. Prior to surgery, the rabbits underwent abdominal aorta ultrasonic testing and blood collection from the ear veins. Of the original 20 rabbits, 10 rabbits were euthanized two weeks after the operation following ultrasonic testing, PET/CT scanning and blood collection, and their arterial tissue samples were prepared for pathological and immunohistochemical staining. The remaining 10 rabbits were euthanized four weeks after the operation following ultrasonic testing, PET/CT scanning and blood collection, and the arterial tissue samples were prepared for pathological and immunohistochemical staining. RESULTS: Compared with the preoperative measurement, the maximum growth rate of the aneurysm diameter is 89.21 ± 0.02% (the absolute increase in diameter is 2.040 ± 0.376 mm) two weeks after the operation. Compared with the two-week postoperative value, the maximum growth rate of the aneurysm diameter is 15.8 ± 0.01% (the absolute increase in diameter is 0.684 ± 0.115 mm) four weeks after the operation. Compared with the preoperative values, the blood MMP-2 and MMP-9 levels significantly increase two weeks after surgery, P < 0.05. Compared with the two-week postoperative values, the blood MMP-2 and MMP-9 levels significantly decrease after four weeks post-surgery, P < 0.05. At two weeks after the operation, the SUVmax and the TBR of the 18F-FDG PET/CT of the AAA wall are 0.90 ± 0.03 and 1.19 ± 0.09, respectively. At four weeks after the operation, the SUVmax and the TBR of the 18F-FDG PET/CT of the AAA wall are 0.35 ± 0.05 and 1.15 ± 0.12, respectively. Compared with two weeks after the operation, the SUVmax significantly decreases at four weeks after the operation, P < 0.05. Compared with two weeks after the operation, there is no significant difference in the TBR at four weeks after the operation, P > 0.05. Immunohistochemical staining shows that the CD68-positive cell rate at four weeks after the operation significantly decreases ( P < 0.05) compared with the CD68-positive cell rate at two weeks after the operation. CONCLUSION: In the early stages of abdominal aortic aneurysm development, the inflammatory response of the arterial wall is significant, the local metabolic activity is strengthened, the SUVmax value of 18F-FDG is high, and the abdominal aortic aneurysm diameter experiences rapid growth. In the later stages of abdominal aortic aneurysm development, the diameter continues to increase; however, there are decreases in the wall inflammatory response, the local metabolic activity, and the SUVmax value of 18F-FDG. Thus, inflammation plays an important role in the early development of abdominal aortic aneurysm.

mTOR mutation disrupts larval zebrafish tail fin regeneration via regulating proliferation of blastema cells and mitochondrial functions.

BACKGROUND: The larval zebrafish tail fin can completely regenerate in 3 days post amputation. mTOR, the main regulator of cell growth and metabolism, plays an essential role in regeneration. Lots of studies have documented the role of mTOR in regeneration. However, the mechanisms involved are still not fully elucidated. MATERIALS AND RESULTS: This study aimed to explore the role and mechanism of mTOR in the regeneration of larval zebrafish tail fins. Initially, the spatial and temporal expression of mTOR signaling in the larval fin was examined, revealing its activation following tail fin amputation. Subsequently, a mTOR knockout (mTOR-KO) zebrafish line was created using CRISPR/Cas9 gene editing technology. The investigation demonstrated that mTOR depletion diminished the proliferative capacity of epithelial and mesenchymal cells during fin regeneration, with no discernible impact on cell apoptosis. Insight from SMART-seq analysis uncovered alterations in the cell cycle, mitochondrial functions and metabolic pathways when mTOR signaling was suppressed during fin regeneration. Furthermore, mTOR was confirmed to enhance mitochondrial functions and Ca2 + activation following fin amputation. These findings suggest a potential role for mTOR in promoting mitochondrial fission to facilitate tail fin regeneration. CONCLUSION: In summary, our results demonstrated that mTOR played a key role in larval zebrafish tail fin regeneration, via promoting mitochondrial fission and proliferation of blastema cells.

Sulfonate derivatives bearing an amide unit: design, synthesis and biological activity studies.

Pest disasters which occurs on crops is a serious problem that not only cause crop yield loss or even crop failure but can also spread a number of plant diseases.Sulfonate derivatives have been widely used in insecticide and fungicide research in recent years. On this basis, a series of sulfonate derivatives bearing an amide unit are synthesized and the biological activities are evaluated. The bioassay results showed that compounds A8, A13, A16, B1, B3, B4, B5, B10, B12 - 20, C3, C5, C9, C10, C14, C15, C17 and C19 showed 100% activity at a concentration of 500 µg/mL against the Plutella xylostella (P. xylostella). Among them, B15 which contains a thiadiazole sulfonate structure still shows 100% activity at 50 µg/mL concentration against P. xylostella and had the lowest median lethal concentration (LC50) (7.61 µg/mL) among the target compounds. Further mechanism studies are conducted on compounds with better insecticidal activity. Molecular docking results shows that B15 formed hydrophobic interactions π-π and hydrogen bonds with the indole ring of Trp532 and the carboxyl group of Asp384, respectively, with similar interaction distances or bond lengths as those of diflubenzuron. Moreover, chitinase inhibition assays are performed to further demonstrate its mode of action. In addition, the anti-bacterial activity of the series of compounds is also tested and the results showed that the series of compounds has moderate biological activity against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), with inhibition rates of 91%, 92% and 92%, 88% at the concentration of 100 µg/mL, respectively. Our study indicates that B15 can be used as a novel insecticide for crop protection.

Innovative Hydrogel-Patch Combination for Large Annulus Fibrosus Defects: A Prospective Approach to Address Herniation Recurrence.

BACKGROUND CONTEXT: Large annulus fibrosus (AF) defects often lead to a high rate of reherniation, particularly in the medial AF region, which has limited self-healing capabilities. The increasing prevalence of herniated discs underscores the need for effective repair strategies. PURPOSE: The objectives of this study were to design an AF repair technique to reduce solve the current problems of insufficient mechanical properties and poor sealing capacity. STUDY DESIGN: In vitro biomechanical experiments and finite element analysis. METHODS: The materials used in this study were patches and hydrogels with good biocompatibility and sufficient mechanical properties to withstand loading in the lumbar spine. Five repair techniques were assessed in this study: hydrogel filler (HF), AF patch medial barrier (MB), AF patch medial barrier and hydrogel filler (MB&HF), AF patch medial-lateral barrier (MLB), and AF patch medial-lateral barrier and hydrogel filler (MLB&HF). The repair techniques were subjected to in vitro testing (400 N axial compression and 0-500 N fatigue loading at 5Hz) and finite element analysis (400 N axial compression) to evaluate the effectiveness at repairing large AF defects. The evaluation included repair tightness, spinal stability, and fatigue resistance. RESULTS: From the in vitro testing, the failure load of the repair techniques was in the following order HF < MB < MB&HF < MLB < MLB&HF. Both HF and MB groups failed to effectively increase intervertebral disc (IVD) stiffness, resulting in a reduction in spatial stability. The MLB, MB&HF, and MLB&HF groups partially restored IVD stiffness, with MLB&HF showing the most effective recovery (-24.13% ± 3.59%). From the finite element models, incorporating a hydrogel filler was best able to maintain the IVD height. Patch repair alone could not adequately reduce the high AF stress due to AF injury, but with hydrogel support, stress was substantially low and more uniformly distributed. All repair techniques demonstrated reduced stress around the damaged area on the AF, in comparison to the unrepaired model. The NP pressure in the HF group was closest to the intact group, and the patch repair reduced the NP pressure. The maximum patch deformation and suture stress were ranked as MB > MLB > MB&HF > MLB&HF. CONCLUSIONS: The combined use of patches and hydrogels exhibited promising mechanical properties post-discectomy, providing a promising solution for addressing large AF defects and improving disc stability. CLINICAL SIGNIFICANCE: This study introduces a promising method for repairing large annular fissure (AF) defects after disc herniation, combining patch repair with a hydrogel filler. These techniques hold potential for developing clinical AF repair products to address this challenging issue.

Autophagy and apoptosis: regulatory factors of chondrocyte phenotype transition in osteoarthritis.

Osteoarthritis (OA) is the main pathogenic factor in diseases that cause joint deformities. As the main manifestation of the progress of OA, cartilage degradation has been closely associated with the degeneration of chondrocytes, which is induced by inflammatory factors and other trauma factors. Autophagy and apoptosis are the main mechanisms for cells to maintain homeostasis and play crucial roles in OA. Under the influence of external environmental factors (such as aging and injury), the metabolism of cells can be altered, which may affect the extent of autophagy and apoptosis. With the progression of OA, these changes can alter the cell phenotypes, and the cells of different phenotypes display distinct differences in morphology and function. In this review, we have summarized the alteration in cell metabolism, autophagy, and the extent of apoptosis during OA progression and its effects on the cell phenotypes to provide new ideas for further research on the mechanisms of phenotypic transition and therapeutic strategies so as to reverse the cell phenotypes.

A comparison between knotted and knotless medial row of suture bridge technique in arthroscopic rotator cuff repair surgery: a meta-analysis.

BACKGROUND: The shoulder arthroscopic suture bridge technique is currently very popular, but scientific evidence relating to the clinical outcomes of the medial row with or without knots has not been systematic reviewed. PURPOSE: The purpose of this study was to compare the clinical outcomes of knotted versus knotless double-row suture bridges for rotator cuff repairs. STUDY DESIGN: Meta-analysis. METHOD: Five databases that contain literature in English were searched (Medline, PubMed, Embase, Web of Science, and the Cochrane Library), with a focus on works published between 2011 and 2022. Clinical data relating to arthroscopic rotator cuff repair with the suture bridge approach was examined and the outcomes of medial row knotting contrasted with that of the knotless technique. The search phrase used was: (double row) AND (rotator cuff) AND (repair), and the search method is subject term plus free word search. Literature quality evaluation was performed using the Cochrane "risk of bias" tool 1.0 and the Newcastle-Ottawa scale quality assessment instrument. RESULTS: One randomized controlled trial, four prospective cohort studies, and five retrospective cohort studies were included in this meta-analysis. Data pertaining to 1146 patients was drawn from these ten original papers and analyzed. Meta-analyses that were performed on 11 postoperative outcomes revealed that none of the differences were statistically significant (P > 0.05) and that the publications were unbiased (P > 0.05). Postoperative retear rate and postoperative retear categorization were the outcomes assessed. Scores on postoperative pain, forward flexion, abduction, and external rotation mobility were collated and evaluated. The University of California, Los Angeles scoring systems in the first year following surgery, the American Shoulder and Elbow Surgeons score and Constant scales in the first and second years after surgery were the secondary outcomes spotlighted in this study. CONCLUSION: The clinical outcomes of shoulder arthroscopic rotator cuff repair with the suture bridge technique with or without a knotted medial row was proven to be equivalent. These outcomes are about postoperative retear, postoperative retear classification, postoperative shoulder function score, postoperative shoulder mobility, and postoperative pain, respectively. It should be noted that the conclusions are based on short-term clinical follow-up data.

Biomechanical evaluation of a novel intervertebral disc repair technique for large box-shaped ruptures.

Objective: The purpose of this study was to analyze the feasibility of repairing a ruptured intervertebral disc using a patch secured to the inner surface of the annulus fibrosus (AF). Different material properties and geometries for the patch were evaluated. Methods: Using finite element analysis, this study created a large box-shaped rupture in the posterior-lateral region of the AF and then repaired it with a circular and square inner patch. The elastic modulus of the patches ranged from 1 to 50 MPa to determine the effect on the nucleus pulposus (NP) pressure, vertical displacement, disc bulge, AF stress, segmental range of motion (ROM), patch stress, and suture stress. The results were compared against the intact spine to determine the most suitable shape and properties for the repair patch. Results: The intervertebral height and ROM of the repaired lumbar spine was similar to the intact spine and was independent of the patch material properties and geometry. The patches with a modulus of 2-3 MPa resulted in an NP pressure and AF stresses closest to the healthy disc, and produced minimal contact pressure on the cleft surfaces and minimal stress on the suture and patch of all models. Circular patches caused lower NP pressure, AF stress and patch stress than the square patch, but also caused greater stress on the suture. Conclusion: A circular patch with an elastic modulus of 2-3 MPa secured to the inner region of the ruptured annulus fibrosus was able to immediately close the rupture and maintain an NP pressure and AF stress similar to the intact intervertebral disc. This patch had the lowest risk of complications and produced the greatest restorative effect of all patches simulated in this study.

Dynamic Tensile Stress Promotes Regeneration of Achilles Tendon in a Panda Rope Bridge Technique Mice Model.

Regeneration of ruptured Achilles tendon remains a clinical challenge owing to its limited regenerative capacity. Dynamic tensile stress plays a positive role in the regeneration of tendon, although the specific underlying mechanisms remain unclear. In this study, the Achilles tendon defect-regeneration model was created in male C57BL/6 mice aged 8 weeks. The animals were randomly assigned to four groups-repair, non-repair, repair with fixation, and non-repair with fixation. The repair group and repair with fixation group adopted the panda rope bridge technique (PRBT) repair method. Our results demonstrated the presence of more densely aligned and mature collagen fibers, as well as more tendon-related makers, in the repair group at both 2- and 4-week post-surgery. Furthermore, the biomechanical strength of the regenerated tendon in the repair group was highly improved. Most importantly, the expressions of integrin αv and its downstream and the phosphorylation levels of FAK and ERK were remarkably higher in the repair group than in the other groups. Furthermore, blocking FAK or ERK with selective inhibitors PF573228 and U0126 resulted in obvious adverse effects on the histological structure of the regenerated Achilles tendon. In summary, this study demonstrated that dynamic tensile stress based on the PRBT could effectively promote the regeneration of the Achilles tendon, suggesting that dynamic tensile stress enhances the cell proliferation and tenogenic differentiation via the activation of the integrin/FAK/ERK signaling pathway.

Comparison Between Multisite Injection and Single Rotator Interval Injection of Corticosteroid in Primary Frozen Shoulder (Adhesive Capsulitis): A Randomized Controlled Trial.

BACKGROUND: Steroid injection is a commonly used conservative treatment for primary frozen shoulder (PFS), but the optimal injection site remains undetermined. OBJECTIVES: We conducted a prospective randomized controlled trial of multisite combined injection (MCI) vs single rotator interval injection (SRI). STUDY DESIGN: A randomized double-blinded controlled trial. SETTING: Center for Joint Surgery, Department of Orthopaedic Surgery, the Second Affiliated Hospital of Chongqing Medical University. METHODS: Sixty-four patients with PFS were randomly assigned to 2 groups. The experimental group received MCI in the rotator interval, intraarticular, and subacromial bursa; the control group received an SRI. Both groups were injected with one mL of 40 mg triamcinolone acetonide and 4 mL of 2% lidocaine. The injection process was completed under ultrasound guidance. Follow-up points were 4, 8, and 12 weeks postinjection. The outcome measures included the Visual Analog Scale (VAS) score, the American Shoulder and Elbow Surgeons (ASES) score, the Constant-Murley Shoulder (CMS) score, passive range of motion of the shoulder, and patient satisfaction rating. RESULTS: Thirty patients in the MCI group and 29 patients in the SRI group were included in the data analysis. All the outcomes in the 2 groups were significantly better postinjection than preinjection. The MCI group had a lower VAS score than the SRI group at 4 weeks (3.1 ± 1.2 vs 4.3 ± 1.6) and 8 weeks (2.2 ± 1.2 vs. 3.4 ± 1.2) (P < 0.05). Compared with the SRI group, the MCI group had a significant improvement in flexion and abduction (P < 0.01). Additionally, the ASES and CMS scores in the MCI group were better than those in the SRI group at 4, 8 and 12 weeks (P < 0.01). LIMITATIONS: Limitations include the sample size of this study is small and a that it was conducted at a single-center. CONCLUSIONS: Both MCI and SRI effectively alleviated pain and restored range of motion in patients with PFS. However, the MCI group had obviously lower early pain scores, better flexion and abduction, and better function scores than the SRI group; no additional adverse events were observed.

Outcomes After Double-Layer Repair Versus En Masse Repair for Delaminated Rotator Cuff Injury: A Systematic Review and Meta-analysis.

Background: Delamination of rotator cuff tears during arthroscopic shoulder surgery has an incidence of 38% to 92%. Double-layer (DL) repair and en masse (EM) repair are most commonly used in this situation. Purpose: To compare the clinical results of the DL versus EM repair techniques for delaminated rotator cuff tears using a meta-analysis. Study Design: Systematic review; level of evidence, 3. Methods: We identified relevant studies comparing the clinical results of DL and EM repair for delaminated rotator cuff injuries in the PubMed, Embase, and Cochrane databases after the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The primary outcomes were the Constant score and retear rate. Additionally, we compared other postoperative shoulder functional scores, shoulder range of motion, and visual analog scale (VAS) pain scores between the 2 suture methods using a meta-analysis. The mean difference (MD) was compared for continuous outcomes, and the odds ratios (ORs) were compared for categorical outcomes. Results: Of the 197 studies initially identified, 6 studies were included in this analysis. There were significant differences in the Constant score (MD, 8.64 [95% CI, 4.47 to 12.8]; P < .05) and external rotation (MD, 5.10 [95% CI, 2.63 to 7.56]; P < .05) between the 2 techniques, with DL repair having superior outcomes. No significant differences were observed between the 2 techniques in forward flexion (MD, 0.62 [95% CI, -1.18 to 2.43]; P = .50), VAS pain (MD, -0.03 [95% CI, -0.34 to 0.27]; P = .84), or retear rate (OR, 0.73 [95% CI, 0.37 to 1.41]; P = .35). Conclusion: Results of this review and meta-analysis suggest that DL repair was more beneficial than EM repair in terms of the Constant score and shoulder external rotation in patients with delaminated rotator cuff injuries.

Allomelanin-based biomimetic nanotherapeutics for orthotopic glioblastoma targeted photothermal immunotherapy.

Immune checkpoint blockade (ICB) therapy has shown great potential in the treatment of malignant tumors, but its therapeutic effect on glioblastoma (GBM) is unsatisfactory because of the low immunogenicity and T cell infiltration, as well as the presence of blood-brain barrier (BBB) that blocks most of ICB agents to the GBM tissues. Herein, we developed a biomimetic nanoplatform of AMNP@CLP@CCM for GBM-targeted photothermal therapy (PTT) and ICB synergistic therapy by loading immune checkpoint inhibitor CLP002 into the allomelanin nanoparticles (AMNPs) and followed by coating cancer cell membranes (CCM). The resulting AMNP@CLP@CCM can successfully cross the BBB and deliver CLP002 to GBM tissues due to the homing effect of CCM. As a natural photothermal conversion agent, AMNPs are used for tumor PTT. The increased local temperature by PTT not only enhances BBB penetration but also upregulates the PD-L1 level on GBM cells. Importantly, PTT can effectively stimulate immunogenic cell death to induce tumor-associated antigen exposure and promote T lymphocyte infiltration, which can further amplify the antitumor immune responses of GBM cells to CLP002-mediated ICB therapy, resulting in significant growth inhibition of the orthotopic GBM. Therefore, AMNP@CLP@CCM has great potential for the treatment of orthotopic GBM by PTT and ICB synergistic therapy. STATEMENT OF SIGNIFICANCE: The effect of ICB therapy on GBM is limited by the low immunogenicity and insufficient T-cell infiltration. Here we developed a biomimetic nanoplatform of AMNP@CLP@CCM for GBM-targeted PTT and ICB synergistic therapy. In this nanoplatform, AMNPs are used as both photothermal conversion agents for PTT and nanocarriers for CLP002 delivery. PTT not only enhances BBB penetration but also upregulates the PD-L1 level on GBM cells by increasing local temperature. Additionally, PTT also induces tumor-associated antigen exposure and promotes T lymphocyte infiltration to amplify the antitumor immune responses of GBM cells to CLP002-mediated ICB therapy, resulting in significant growth inhibition of the orthotopic GBM. Thus, this nanoplatform holds great potential for orthotopic GBM treatment.

Deletion of DYRK1A Accelerates Osteoarthritis Progression Through Suppression of EGFR-ERK Signaling.

Dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) signaling is involved in the dynamic balance of catabolism and anabolism in articular chondrocytes. This study aimed to investigate the roles and mechanism of DYRK1A in the pathogenesis of osteoarthritis (OA). The expressions of DYRK1A and its downstream signal epidermal growth factor receptor (EGFR) were detected in the cartilage of adult wild-type mice with destabilized medial meniscus (DMM) and articular cartilage of patients with OA. We measured the progression of osteoarthritis in chondrocyte-specific knockout DYRK1A(DYRK1A-cKO) mice after DMM surgery. Knee cartilage was histologically scored and assessed the effects of DYRK1A deletion on chondrocyte catabolism and anabolism. The effect of inhibiting EGFR signaling in chondrocytes from DYRK1A-cKO mice was analyzed. Trauma-induced OA mice and OA patients showed downregulation of DYRK1A and EGFR signaling pathways. Conditional DYRK1A deletion aggravates DMM-induced cartilage degeneration, reduces the thickness of the superficial cartilage, and increases the number of hypertrophic chondrocytes. The expression of collagen type II, p-ERK, and aggrecan was also downregulated, and the expression of collagen type X was upregulated in the articular cartilage of these mice. Our findings suggest that DYRK1A delays the progression of knee osteoarthritis in mice, at least in part, by maintaining EGFR-ERK signaling in articular chondrocytes.

Risk Factors and Corresponding Management for Suture Anchor Pullout during Arthroscopic Rotator Cuff Repair.

INTRODUCTION: Due to the aging of the population, the incidence of rotator cuff tears is growing. For rotator cuff repair, arthroscopic suture-anchor repair has gradually replaced open transosseous repair, so suture anchors are now considered increasingly important in rotator cuff tear reconstruction. There are some but limited studies of suture anchor pullout after arthroscopic rotator cuff repair. However, there is no body of knowledge in this area, which makes it difficult for clinicians to predict the risk of anchor pullout comprehensively and manage it accordingly. METHODS: The literature search included rotator cuff repair as well as anchor pullout strength. A review of the literature was performed including all articles published in PubMed until September 2021. Articles of all in vitro biomechanical and clinical trial levels in English were included. After assessing all abstracts (n = 275), the full text and the bibliographies of the relevant articles were analyzed for the questions posed (n = 80). Articles including outcomes without the area of interest were excluded (n = 22). The final literature research revealed 58 relevant articles. Narrative synthesis was undertaken to bring together the findings from studies included in this review. RESULT: Based on the presented studies, the overall incidence of anchor pullout is not low, and the incidence of intraoperative anchor pullout is slightly higher than in the early postoperative period. The risk factors for anchor pullout are mainly related to bone quality, insertion depth, insertion angle, size of rotator cuff tear, preoperative corticosteroid injections, anchor design, the materials used to produce anchors, etc. In response to the above issues, we have introduced and evaluated management techniques. They include changing the implant site of anchors, cement augmentation for suture anchors, increasing the number of suture limbs, using all-suture anchors, using an arthroscopic transosseous knotless anchor, the Buddy anchor technique, Steinmann pin anchoring, and transosseous suture repair technology. DISCUSSION: However, not many of the management techniques have been widely used in clinical practice. Most of them come from in vitro biomechanical studies, so in vivo randomized controlled trials with larger sample sizes are needed to see if they can help patients in the long run.

Panda rope bridge technique versus open repair of acute Achilles tendon rupture: A comparative clinical study.

PURPOSE: The treatment options of acute Achilles tendon rupture (AATR) remain controversial. This article aims to compare the efficacy of a new surgical procedure, the panda rope bridge technique (PRBT) with open surgery of AATR. METHODS: Ninety-eight patients with AATR were recruited, 53 underwent the PBRT, and 45 underwent open surgery. The operation time, postoperative American Orthopaedic Foot and Ankle Score, Achilles Tendon Rupture Score, complications and time to return to work and restore exercise were documented. RESULTS: The average operation time, intraoperative blood loss and complication rate were 35.1 min, 18.2 ml and 3.8%, respectively, in the PRBT group, which were significantly lower than those of the open surgery group (P<0.001). The post-operative American Orthopaedic Foot and Ankle Score of 99.6 and the Achilles Tendon Rupture Score of 97.5 in the PRBT group were significantly higher than that of the open surgery group (P<0.001). The time to return to work and return to exercise were shorter in the PRBT group (P<0.001). CONCLUSION: Compared to open surgery, PRBT is a better approach to the management of AATR. PRBT offers accelerated recovery, lower occurrence of post-operative complications and improved recovery of ankle joint function.