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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

m6A regulator-mediated methylation modification patterns and immune microenvironment infiltration characterization in osteoarthritis.

Osteoarthritis (OA) is a common disease in orthopedics. RNA N6-methyladenosine (m6A) exerts an essential effect in a variety of biological processes in the eukaryotes. In this study, we determined the effect of m6A regulators in the OA along with performing the subtype classification. Differential analysis of OA and normal samples in the database of Gene Expression Omnibus identified 9 significantly differentially expressed m6A regulators. These regulators were monitored by a random forest algorithm so as to evaluate the risk of developing OA disease. On the basis of these 9 moderators, a nomogram was established. The results of decision curve analysis suggested that the patients could benefit from a nomogram model. The OA sample was classified as 2 m6A models through a consensus clustering algorithm in accordance with these 9 regulators. These 2 m6A patterns were then assessed with principal component analysis. We also determined the m6A scores for the 2 m6A patterns and their correlation with immune infiltration. The results indicated that type A had a higher m6A score than type B. Thus, we suggest that the m6A pattern may provide a new approach for diagnose and provide novel ideas for molecular targeted therapy of OA.

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.

Biomechanical evaluation of a short-rod technique for lumbar fixation surgery.

Objective: The purpose of this study was to analyze the stability and instrument-related complications associated with fixation of the lumbar spine using the Short-Rod (SR) technique. Methods: Using finite element analysis, this study assessed the stability of a bilateral lumbar fixation system when inserting the pedicle screws at angles of 10°, 15°, and 20° to the endplate in the sagittal plane. Using the most stable construct with a screw angle, the model was then assessed with different rod lengths of 25, 30, 35, and 45 mm. The optimal screw inclination angle and rod length were incorporated into the SR model and compared against traditional parallel screw insertion (pedicle screws in parallel to the endplate, PPS) in terms of the stability and risk of instrument-related complications. The following parameters were evaluated using the validated L4-L5 lumbar finite element model: axial stiffness, range of motion (ROM), stress on the endplate and facet joint, von-Mises stress on the contact surface between the screw and rod (CSSR), and screw displacement. Results: The results showed that the SR model with a 15° screw inclination angle and 35 mm rod length was superior in terms of construct stability and risk of complications. Compared to the PPS model, the SR model had lower stiffness, lower ROM, less screw displacement, and lower stress on the facet cartilage, the CSSR, and screws. However, the SR model also suffered more stress on the endplate in flexion and lateral bending. Conclusion: The SR technique with a 15° screw inclination and 35 mm rod length offers good lumbar stability with a low risk of instrument-related complications.

A Strong Correlation Between the Severity of Flatfoot and Symptoms of Knee Osteoarthritis in 95 Patients.

Objective: The purpose of this study is to assess the association between the presence and severity of flatfoot and symptoms of knee OA. Methods: 95 participants with knee OA were recruited from a patient cohort at a regional hospital. Symptoms of knee OA, including knee degeneration, femorotibial alignment, pain, stiffness and dysfunction were assessed using the Kellgren-Lawrence (K-L) grading system, femoral-tibial angle (FTA), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Participants were divided into groups with flatfoot (mild, moderate and severe) and without flatfoot based on the Clarke's angle. Linear regression and ordinal logistic regression were used for statistical analysis, as appropriate. Results: Having flatfoot was associated with a significantly increased risk of having a higher K-L grade (OR: 20.03; 95% CI, 5.88, 68.27; p < 0.001), smaller FTA (Beta: -2.96; 95% CI, -4.41, -1.50; p < 0.001), higher pain score (Beta: 0.47; 95% CI, 0.24, 0.69; p < 0.001) and greater loss of function (Beta: 0.25; 95% CI, 0.02, 0.48; p = 0.03). Severe grades of flat feet were associated with a higher K-L grade (OR: 0.19; 95% CI, 0.08, 0.44; p < 0.001), smaller FTA (Beta: 1.51; 95% CI, 0.66, 2.35; p = 0.001), higher pain score (Beta: -0.25; 95% CI, -0.39, -0.11; p = 0.001), greater stiffness (Beta: -0.24; 95% CI, -0.38, -0.09; p = 0.002) and greater loss of function (Beta: -0.27; 95% CI, -0.41, -0.14; p < 0.001). Conclusion: The results indicated that the severity of flattening is significantly associated with symptoms of knee OA. For the conservative management of knee OA, both flatfoot and its severity should be carefully considered.

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.

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.

In adults, early mobilization may be beneficial for distal radius fractures treated with open reduction and internal fixation: a systematic review and meta-analysis.

OBJECTIVES: It remains debatable if early mobilization (EM) yields a better clinical outcome than the late mobilization (LM) in adults with an acute and displaced distal radial fracture (DRF) of open reduction internal fixation (ORIF). Therefore, we aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs), comparing clinical results with the safety of EM with LM following ORIF. METHODS: Databases such as Medline, Cochrane Central Register, and Embase were searched from Jan 1, 2000, to July 31, 2021, and RCTs comparing EM with LM for DRF with ORIF were included in the analysis. The primary outcome of study included disabilities of the Arm, Shoulder, and Hand (DASH) score at different follow-up times. Wherever the secondary outcomes included patient-rated wrist evaluation (PRWE), grip strength (GS), visual analog scale (VAS), wrist range of motion (WROM), and associated complications, the two independent reviewers did data extraction for the analysis. Effect sizes of outcome for each group were pooled using random-effects models; thereafter, the results were represented in the forest plots. RESULTS: Nine RCTs with 293 EM and 303 LM participants were identified and included in the study. Our analysis showed that the DASH score of the EM group was significantly better than LM group at the six weeks postoperatively (- 10.15; 95% CI - 15.74 to - 4.57, P < 0.01). Besides, the EM group also had better outcomes in PRWE, GS and WROM at 6 weeks. However, EM showed potential higher rate for implant loosening and/or fracture re-displacement complication (3.00; 95% CI 1.02-8.83, P = 0.05). CONCLUSION: Functionally, at earlier stages, EM for patients with DRF of ORIF may have a beneficial effect than LM. The mean differences in the DASH score at 6 weeks surpassed the minimal clinically important difference; however, the potentially higher risk of implant loosening and/or fracture re-displacement cannot be ignored. Due to the lack of definitive evidence, multicenter and large sample RCTs are required for determining the optimal rehabilitation protocol for DRF with ORIF. PROSPERO registration number: CRD42021240214 2021/2/28.