Engineering Bioactive M2 Macrophage-Polarized, Anti-inflammatory, miRNA-Based Liposomes for Functional Muscle Repair: From Exosomal Mechanisms to Biomaterials.

Severe inflammation and myogenic differentiation disorder are the major obstacles to skeletal muscle healing after injury. MicroRNAs (miRNAs) play an important role as regulatory molecules during the process of muscle healing, but the detailed mechanism of miRNA-mediated intercellular communication between myoblasts and macrophages remains unclear. Here, it is reported that myoblasts secrete miRNAs-enriched exosomes in the inflammatory environment, through which miR-224 is transferred into macrophages to inhibit M2 polarization. Further data demonstrate that WNT-9a may be a direct target of miR-224 for macrophage polarization. In turn, the secretome of M1 macrophages impairs myogenic differentiation and promotes proliferation. Single-cell integration analysis suggests that the elevation of exosome-derived miR-224 is caused by the activation of the key factor E2F1 in myoblasts and demonstrates the RB/E2F1/miR-224/WNT-9a axis. In vivo results show that treatment with antagomir-224 or liposomes containing miR-224 inhibitors suppresses fibrosis and improves muscle recovery. These findings indicate the importance of the crosstalk between myoblasts and macrophages via miRNA-containing exosomes in the regulation of macrophage polarization and myogenic differentiation/proliferation during muscle healing. This study provides a strategy for treating muscle injury through designing an M2 polarization-enabling anti-inflammatory and miRNA-based bioactive material.

The role of carbonic anhydrase III and autophagy in type 2 diabetes with cardio-cerebrovascular disease.

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases among the elderly people. The T2DM increases the risk of cardio-cerebrovascular disease (CCD), and the main pathological change of the CCD is atherosclerosis (AS). Meanwhile, the carbonic anhydrases (CAs) are involved in the formation and progression of plaques in AS. However, the exact physiological mechanism of carbonic anhydrase III (CAIII) has not been clear yet, and there are also no correlation study between CAIII protein and T2DM with CCD. The 8-week old diabetic mice (db/db-/- mice) and wild-type mice (wt mice) were feed by a normal diet till 32 weeks, and detected the carotid artery vascular opening angle using the method of biomechanics; The changes of cerebral cortex and myocardium were watched by the ultrastructure, and the autophagy were observed by electron microscope; The tissue structure, inflammation and cell injury were observed by Hematoxylin and eosin (HE) staining; The apoptosis of cells were observed by TUNEL staining; The protein levels of CAIII, IL-17, p53 were detected by immunohistochemical and Western Blot, and the Beclin-1, LC3, NF-κB were detected by Western Blot. All statistical analysis is performed using PRISM software. Compared with wt mice, db/db-/- mice' carotid artery open angle increased significantly. Electron microscope results indicated that autophagy in db/db-/- mice cerebral cortex and heart tissue decreased and intracellular organelle ultrastructure were damaged. HE staining indicated that, db/db-/- mice' cerebral cortex and heart tissue stained lighter, inflammatory cells infiltration, cell edema were obvious, myocardial fibers were disorder, and myocardial cells showed different degrees of degeneration. Compared with wt mice, TUNEL staining showed that there was obviously increase in db/db-/- mice cortex and heart tissue cell apoptosis. The results of immunohistochemistry and Western Blot indicated that CAIII, Beclin-1 and LC3II/I expression levels conspicuously decreased in cortex and heart tissue of db/db-/- mice, and the expression level of IL-17, NF-κB and p53 obviously increased. The carotid artery' vascular stiffness was increased and which was probably related with formation of AS in diabetic mice. And the autophagy participated in the occurrence and development of diabetic CCD. CAIII protein might somehow be involved in the regulation of autophagy probably through affecting cell apoptosis and inflammation, but the underlying mechanism remains to be further studied.

CAIII expression in skeletal muscle is regulated by Ca2+-CaMKII-MEF2C signaling.

Carbonic anhydrase III (CAIII) is selectively expressed in slow-twitch myofibers in skeletal muscle. The fast-twitch to slow-twitch transformation of myofibers following denervation is accompanied by increased CAIII expression, suggesting that the effects of nerve impulses on skeletal-muscle remodeling influence CAIII expression. Here, we determined the molecular mechanisms underlying the effects of nerve conduction on CAIII expression. The results indicated that changes in skeletal-muscle [Ca2+]i altered CAIII expression. Moreover, results from the RNA-interference and over-expression experiments identified myocyte enhancer factor 2C (MEF2C) as the key transcription factor regulating [Ca2+]i-mediated changes in CAIII transcription. Additionally, chromatin immunoprecipitation experiments and luciferase assays confirmed MEF2C interaction and direct binding of the CAIII promoter between -416 and -200 base pair. Investigations of upstream cytoplasmic signaling pathways responsible for MEF2C activation revealed Ca2+/calmodulin-dependent protein kinase II (CaMKII) as the key factor involved in MEF2C-mediated regulation of CAIII expression. This study demonstrates that the Ca2+-CaMKII-MEF2C signaling pathway is the key factor involved in regulating CAIII expression in skeletal muscle. These results provide a theoretical basis supporting further investigations of changes in CAIII levels under different pathophysiological conditions and will facilitate a broader understanding of the biological functions of CAIII.

EGb761 improves the cognitive function of elderly db/db-/- diabetic mice by regulating the beclin-1 and NF-κB signaling pathways.

To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db-/- mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db-/- control, db/db-/- 50 mg, db/db-/- 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db-/- mice decreased (P < 0.05), and EGb761 could significantly improve the learning and memory function of db/db-/- mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db-/- mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db-/- group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db-/- mice (P < 0.05). NF-κB levels were obviously higher in the db/db-/- group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db-/- mice (P < 0.05). There was a trend of increased autophagosomes in db/db-/- mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db-/- mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db-/- mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB.

Clinical and MRI outcomes of HA injection following arthroscopic microfracture for osteochondral lesions of the talus.

PURPOSE: The purpose of this study was to compare the clinical and magnetic resonance imaging (MRI) outcomes of arthroscopic microfracture surgery alone or in combination with hyaluronic acid (HA) injection in the treatment of osteochondral lesions of the talus. METHODS: Thirty-five patients with osteochondral lesions of the talus who underwent arthroscopic microfracture were included and followed up for at least 9 months post-operatively. The patients were randomly divided into non-injection group (n = 17) who received treatment with microfracture surgery alone and injection group (n = 18) who also accepted intra-articular injection of HA post-operatively. Quantitative MRI was used to evaluate the cartilage repair after surgery. American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hind foot Scale scores and Visual Analogue Scale (VAS) scores were used to evaluate clinical outcomes. RESULTS: After operation, the MRI outcomes showed that the thickness index was higher (0.8 ± 0.1 vs. 0.7 ± 0.1) and the T2 index was lower (1.2 ± 0.1 vs. 1.4 ± 0.1) in the injection group than in the non-injection group (P < 0.01). As for the volumes of subchondral bone marrow oedema, there are no significant differences between groups (n.s.). Compared with the non-injection group, the AOFAS score and the VAS score yielded a higher level of improvement in injection group at final follow-up post-operatively (P < 0.05). CONCLUSIONS: Arthroscopic microfracture is a safe and effective procedure for osteochondral lesions of the talus. Intra-articular HA injection as an adjunct to arthroscopic microfracture might offer better functional recovery than microfracture alone. LEVEL OF EVIDENCE: II.

Quantitative magnetic resonance imaging (MRI) evaluation of cartilage repair after microfracture (MF) treatment for adult unstable osteochondritis dissecans (OCD) in the ankle: correlations with clinical outcome.

OBJECTIVES: To quantitatively evaluate cartilage repair after microfracture (MF) for ankle osteochondritis dissecans (OCD) using MRI and analyse correlations between MRI and clinical outcome. METHODS: Forty-eight patients were recruited and underwent MR imaging, including 3D-DESS, T2-mapping and T2-STIR sequences, and completed American Orthopaedic Foot and Ankle Society (AOFAS) scoring. Thickness index, T2 index of repair tissue (RT) and volume of subchondral bone marrow oedema (BME) were calculated. Subjects were divided into two groups: group A (3-12 months post-op), and group B (12-24 months post-op). Student's t test was used to compare the MRI and AOFAS score between two groups and Pearson's correlation coefficient to analyse correlations between them. RESULTS: Thickness index and AOFAS score of group B were higher than group A (P < 0.001, P < 0.001). T2 index and BME of group B were lower than group A (P < 0.001, P = 0.012). Thickness index, T2 index and BME were all correlated with AOFAS score (r = 0.416, r = -0.475, r = -0.353), but BME was correlated with neither thickness index nor T2 index. CONCLUSIONS: Significant improvement from MF can be expected on the basis of the outcomes of quantitative MRI and AOFAS score. MRI was correlated with AOFAS score. BME is insufficient as an independent predictor to evaluate repair quality, but reduction of BME can improve the patient's clinical outcome. KEY POINTS: • Patients with unstable ankle OCD had satisfactory clinical outcome after MF. • Quantitative MRI correlates with clinical outcome after MF for ankle OCD. • The reduction of subchondral BME will improve the patient's clinical outcome. • Quantitative MRI can monitor the process of cartilage repair over time.

The Revolution of exosomes: From biological functions to therapeutic applications in skeletal muscle diseases.

Skeletal muscle diseases, a broad category encompassing a myriad of afflictions such as acute muscle injury and muscular dystrophies, pose a significant health burden globally. These conditions often lead to muscle weakness, compromised mobility, and a diminished quality of life. In light of this, innovative and effective therapeutic strategies are fervently sought after. Exosomes, naturally extracellular vesicles with a diameter of 30-150 nm, pervade biological fluids. These microscopic entities harbor a host of biological molecules, including proteins, nucleic acids, and lipids, bearing a significant resemblance to their parent cells. The roles they play in the biological theater are manifold, influencing crucial physiological and pathological processes within the organism. In the context of skeletal muscle diseases, their potential extends beyond these roles, as they present a promising therapeutic target and a vehicle for targeted drug delivery. This potentially paves the way for significant clinical applications. This review aims to elucidate the mechanisms underpinning exosome action, their myriad biological functions, and the strides made in exosome research and application. A comprehensive exploration of the part played by exosomes in skeletal muscle repair and regeneration is undertaken. In addition, we delve into the use of exosomes in the therapeutic landscape of skeletal muscle diseases, providing a valuable reference for a deeper understanding of exosome applications in this realm. The concluding section encapsulates the prospective avenues for exosome research and the promising future they hold, underscoring the tremendous potential these diminutive vesicles possess in the field of skeletal muscle diseases. The Translational Potential of this Article. The comprehensive exploration of exosome's diverse biological functions and translational potential in the context of skeletal muscle diseases presented in this review underscores their promising future as a therapeutic target with significant clinical applications, thus paving the way for innovative and effective therapeutic strategies in this realm.

Biomaterials-Based Technologies in Skeletal Muscle Tissue Engineering.

For many clinically prevalent severe injuries, the inherent regenerative capacity of skeletal muscle remains inadequate. Skeletal muscle tissue engineering (SMTE) seeks to meet this clinical demand. With continuous progress in biomedicine and related technologies including micro/nanotechnology and 3D printing, numerous studies have uncovered various intrinsic mechanisms regulating skeletal muscle regeneration and developed tailored biomaterial systems based on these understandings. Here, the skeletal muscle structure and regeneration process are discussed and the diverse biomaterial systems derived from various technologies are explored in detail. Biomaterials serve not merely as local niches for cell growth, but also as scaffolds endowed with structural or physicochemical properties that provide tissue regenerative cues such as topographical, electrical, and mechanical signals. They can also act as delivery systems for stem cells and bioactive molecules that have been shown as key participants in endogenous repair cascades. To achieve bench-to-bedside translation, the typical effect enabled by biomaterial systems and the potential underlying molecular mechanisms are also summarized. Insights into the roles of biomaterials in SMTE from cellular and molecular perspectives are provided. Finally, perspectives on the advancement of SMTE are provided, for which gene therapy, exosomes, and hybrid biomaterials may hold promise to make important contributions.

A Mesoporous Silica-Loaded Multi-Functional Hydrogel Enhanced Tendon Healing via Immunomodulatory and Pro-Regenerative Effects.

Tendon injuries are pervasive orthopedic injuries encountered by the general population. Nonetheless, recovery after severe injuries, such as Achilles tendon injury, is limited. Consequently, there is a pressing need to devise interventions, including biomaterials, that foster tendon healing. Regrettably, tissue engineering treatments have faced obstacles in crafting appropriate tissue scaffolds and efficacious nanomedical approaches. To surmount these hurdles, an innovative injectable hydrogel (CP@SiO2), comprising puerarin and chitosan through in situ self-assembly, is pioneered while concurrently delivering mesoporous silica nanoparticles for tendon healing. In this research, CP@SiO2 hydrogel is employed for the treatment of Achilles tendon injuries, conducting extensive in vivo and in vitro experiments to evaluate its efficacy. This reults demonstrates that CP@SiO2 hydrogel enhances the proliferation and differentiation of tendon-derived stem cells, and mitigates inflammation through the modulation of macrophage polarization. Furthermore, using histological and behavioral analyses, it is found that CP@SiO2 hydrogel can improve the histological and biomechanical properties of injured tendons. This findings indicate that this multifaceted injectable CP@SiO2 hydrogel constitutes a suitable bioactive material for tendon repair and presents a promising new strategy for the clinical management of tendon injuries.

Construction of a Diagnostic m7G Regulator-Mediated Scoring Model for Identifying the Characteristics and Immune Landscapes of Osteoarthritis.

With the increasingly serious burden of osteoarthritis (OA) on modern society, it is urgent to propose novel diagnostic biomarkers and differentiation models for OA. 7-methylguanosine (m7G), as one of the most common base modification forms in post transcriptional regulation, through which the seventh position N of guanine (G) of messenger RNA is modified by methyl under the action of methyltransferase; it has been found that it plays a crucial role in different diseases. Therefore, we explored the relationship between OA and m7G. Based on the expression level of 18 m7G-related regulators, we identified nine significant regulators. Then, via a series of methods of machine learning, such as support vector machine recursive feature elimination, random forest and lasso-cox regression analysis, a total of four significant regulators were further identified (DCP2, EIF4E2, LARP1 and SNUPN). Additionally, according to the expression level of the above four regulators, two different m7G-related clusters were divided via consensus cluster analysis. Furthermore, via immune infiltration, differential expression analysis and enrichment analysis, we explored the characteristic of the above two different clusters. An m7G-related scoring model was constructed via the PCA algorithm. Meanwhile, there was a different immune status and correlation for immune checkpoint inhibitors between the above two clusters. The expression difference of the above four regulators was verified via real-time quantitative polymerase chain reaction. Overall, a total of four biomarkers were identified and two different m7G-related subsets of OA with different immune microenvironment were obtained. Meanwhile, the construction of m7G-related Scoring model may provide some new strategies and insights for the therapy and diagnosis of OA patients.

Transtendon technique versus repair after completion of the tear for articular-sided partial rotator cuff tear: a meta-analysis of comparative studies.

BACKGROUND: Transtendon repair and repair after completion of the tear have been widely used to treat partial-thickness rotator cuff tears (PT-RCTs). The present study was aimed to compare the clinical outcomes and tendon integrity following arthroscopic repair of articular PT-RCTs using transtendon repair or repair after completion of the tear. METHODS: We performed a systematic electronic database search on Cochrane Central Register of Controlled Trials, PubMed and Embase to identify articles equating articular-sided PT-RCTs repair. The randomized controlled clinical trials that met our criteria were evaluated for quality of methodology. The results obtained were further analyzed and correlated to present the benefits and drawbacks comparing the two surgical procedures. RESULT: According to our inclusion and exclusion criteria, six articles were included in the present study. A total of 501 patients were analyzed as part of this study. The results indicated that both the surgical treatments provided excellent functional improvements and tendon integrity. However, no significant differences for the visual analogue scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, constant score, range of motion, postoperative adhesive capsulitis, tendon integrity and patient satisfaction were found between the two cohorts (p > 0.05). CONCLUSIONS: Both transtendon technique and repair after completion of the tear for articular-sided partial rotator cuff tear provide improvements in clinical outcome with a low complication rate and a high rate of healing.

Mechanisms of exercise in the treatment of lung cancer - a mini-review.

Lung cancer constitutes a formidable menace to global health and well-being, as its incidence and mortality rate escalate at an alarming pace. In recent years, research has indicated that exercise has potential roles in both the prevention and treatment of lung cancer. However, the exact mechanism of the coordinating effect of exercise on lung cancer treatment is unclear, limiting the use of exercise in clinical practice. The purpose of this review is to explore the mechanisms through which exercise exerts its anticancer effects against lung cancer. This review will analyze the biological basis of exercise's anticancer effects on lung cancer, with a focus on aspects such as the tumor microenvironment, matrix regulation, apoptosis and angiogenesis. Finally, we will discuss future research directions and potential clinical applications.

Long head of biceps tendon transposition for massive and irreparable rotator cuff tears: A systematic review and meta-analysis.

BACKGROUND: Superior capsular reconstruction (SCR) with long head of biceps tendon (LHBT) transposition was developed to massive and irreparable rotator cuff tears (MIRCTs); however, the outcomes of this technique remain unclear. AIM: To perform a systematic review of biomechanical outcomes and a meta-analysis of clinical outcomes after LHBT transposition for MIRCTs. METHODS: We performed a systematic electronic database search on PubMed, EMBASE, and Cochrane Library. Studies of SCR with LHBT transposition were included according to the inclusion and exclusion criteria. Biomechanical studies were assessed for main results and conclusions. Included clinical studies were evaluated for quality of methodology. Data including study characteristics, cohort demographics, and outcomes were extracted. A meta-analysis was conducted of the clinical outcomes. RESULTS: According to our inclusion and exclusion criteria, a total of six biomechanical studies were identified and reported an overall improvement in subacromial contact pressures and prevention of superior humeral migration without limiting range of motion (ROM) after LHBT transposition for MIRCTs. A total of five clinical studies were included in the meta-analysis of LHBT transposition outcomes, consisting of 253 patients. The results indicated that compared to other surgical methods for MIRCTs, LHBT transposition had advantages of more significant improvement in ROM (forward flexion mean difference [MD] = 6.54, 95% confidence interval [CI]: 3.07-10.01; external rotation [MD = 5.15, 95%CI: 1.59-8.17]; the acromiohumeral distance [AHD] [MD = 0.90, 95%CI: 0.21-1.59]) and reducing retear rate (odds ratio = 0.27, 95%CI: 0.15-0.48). No significant difference in American Shoulder and Elbow Surgeons score, visual analogue scale score, and University of California at Los Angles score was demonstrated between these two groups for MIRCTs. CONCLUSION: In general, SCR with LHBT transposition was a reliable and economical technique for treating MIRCTs, both in terms of biomechanical and clinical outcomes, with comparable clinical outcomes, improved ROM, AHD, and reduced the retear rates compared to conventional SCR and other established techniques. More high-quality randomized controlled studies on the long-term outcomes of SCR with LHBT transposition are required to further assess.

Chinese Experts Consensus and Practice Guideline on Discoid Lateral Meniscus.

Discoid lateral meniscus (DLM) is the most common congenital variant of the lateral meniscus, which is prone to degeneration and lesions, and often leads to knee osteoarthritis. At present, there is no consensus on the clinical practice of DLM, and this expert consensus and practice guidelines on DLM was developed and approved by Chinese Society of Sports Medicine according to the Delphi method. Among 32 statements drafted, 14 statements were excluded for redundant information, and 18 statements achieved consensus. This expert consensus focused on the definition, epidemiology, etiology, classification, clinical manifestations, diagnosis, treatment, prognosis, and rehabilitation of DLM. Restoring the normal shape, retaining appropriate width and thickness, and ensuring the stability of the remnant meniscus is critical to sustaining the physiological function of the meniscus and preserving the knee. The partial meniscectomy with or without repair should be the first-line treatment when possible, given that the clinical and radiological long-term outcomes of total or subtotal meniscectomy are worse.

Changes in Macrophage Polarization During Tendon-to-Bone Healing After ACL Reconstruction With Insertion-Preserved Hamstring Tendon: Results in a Rabbit Model.

Background: Decreasing the proinflammatory M1 macrophages or shifting the polarization status from M1 to M2 phenotype is thought to be beneficial for tendon-to-bone healing. In anterior cruciate ligament reconstruction (ACLR), using an insertion-preserved hamstring tendon (IP-HT) graft compared with a free hamstring tendon (FHT) graft has been shown to reduce graft necrosis and improve healing. However, the role of macrophage polarization at the tendon-to-bone interface is unclear. Hypothesis: ACLR using IP-HT graft would facilitate the phenotype shift from M1 to M2 macrophages at the tendon-to-bone interface. Study Design: Controlled laboratory study. Methods: Unilateral ACLR was performed on 42 healthy New Zealand White rabbits (study group, 21 rabbits with IP-HT graft; control group, 21 rabbits with FHT graft). At days 1, 3, and 7 and weeks 3, 6, 12, and 24 postoperatively, 3 rabbits in each group were sacrificed to investigate and compare the expression of surrogate markers for M1 macrophages (inducible nitric oxide synthase [iNOS] and tumor necrosis factor α [TNF-α]) and M2 macrophages (CD206 and transforming growth factor ß [TGF-ß]) via immunohistochemical staining and evaluation. Results: In the control group, the percentage of iNOS- and TNF-α-positive cells from postoperative day 7 and week 3 increased then decreased by week 6; positive expression of CD206 and TGF-ß was weaker and peaked at 3 weeks postoperatively. In the study group, high CD206- and TGF-ß-positive expression was observed from weeks 3 to 12 and peaked at week 6, and positive expression of iNOS- and TNF-α was weaker and peaked on day 7. At both 7 days and 3 weeks, the percentages of iNOS- and TNF-α-positive cells in the control group were both significantly higher than in the study group (P ≤ .04 for all). At 6 weeks, the percentages of CD206- and TGF-ß-positive cells in the study group were both significantly higher than in the control group (P = .02 and P = .04, respectively). Conclusion: More expression of surrogate markers for M2 macrophages was observed in the tendon-to-bone healing process after ACLR using IP-HT versus FTP graft. Clinical Relevance: Using IP-HT grafts in ACLR may facilitate postoperative healing by shifting the local status of macrophage polarization at the tendon-to-bone interface.

Monitoring Rotator Cuff Muscle Fatty Infiltration Progression by Magnetic Resonance Imaging T1 Mapping: Correlation With Direct Evaluation Findings in Rats.

BACKGROUND: Monitoring the fatty infiltration (FI) process in rotator cuff muscles is of value in establishing a treatment plan and predicting the postoperative prognosis. Quantitative T1 mapping shows promise for evaluating muscle degeneration, while its validity in monitoring rotator cuff muscle FI progression needs further investigation. PURPOSE: To determine the validity of T1 mapping in monitoring FI progression of rotator cuff muscles. STUDY DESIGN: Controlled laboratory study. METHODS: Sprague-Dawley rats (N = 108) underwent left supraspinatus (SS) and infraspinatus (IS) tenotomy only (TT), suprascapular nerve transection only (NT), or SS and IS tenotomy plus suprascapular nerve transection (TT+NT). Sham surgery on the right shoulder served as the control. The magnetic resonance imaging examination included T1 mapping performed at 12, 16, and 20 weeks postoperation. SS and IS muscles were harvested to quantitatively evaluate FI via direct evaluation (triglyceride quantification assay and histological analysis) at the same predetermined intervals. The correlation of the imaging data with direct evaluation of rotator cuff muscles was analyzed. RESULTS: T1 values were significantly lower in left SS and IS muscles at 12, 16, and 20 weeks postoperation as compared with those on the right side. T1 values of the left SS and IS muscles were continuously decreased in all groups. The TT+NT group had a greater decrease in T1 value than did the TT and NT groups. Triglyceride quantification assay and histological analysis demonstrated significant and progressive FI of the left SS and IS muscles in the 3 groups. The most serious FI changes were observed in the TT+NT group. T1 values were also well correlated with triglyceride contents and area fractions of fat. CONCLUSION: T1 mapping can be an effective imaging modality for sensitive and quantitative monitoring of FI progression in rotator cuff muscles. CLINICAL RELEVANCE: The findings of this study provide a tool for researchers to noninvasively and quantitatively monitor the process of muscle degeneration, contributing to the evaluation of surgical indication and postoperative prognosis.

Guidelines on the Diagnosis and Treatment of Lateral Meniscal Lesions: A Consensus Statement by the Chinese Society of Sports Medicine.

Background: The lateral meniscus is a unique structure of the knee joint, and its anatomy, function, pathological process, and treatment are distinct from those of the medial meniscus. To date, no consensus on the management of lateral meniscal lesions has been published, and clinical decision-making is challenging. To facilitate this, consensus and practice guidelines for lateral meniscal lesions were developed and endorsed by the Chinese Society of Sports Medicine. Study Design: Consensus statement. Methods: This project followed the Delphi approach to the consensus process, involving steering, rating, and peer review groups. A total of 61 experts in the fields of sports medicine and arthroscopic surgery were invited to participate in the compilation of a consensus statement on lateral meniscal lesions. (The discoid lateral meniscus was addressed by separate consensus.) To begin, the steering group drafted a set of questions and replies regarding lateral meniscal lesions. An online panel discussion was then held to provide initial agreement and comments on the statements, followed by a round of anonymous voting. Results and feedback were sent to the steering group for a second draft. A second round of voting was then held, and each statement was discussed during a combined meeting of the steering and rating groups. Finally, a consensus draft was evaluated by a review group. Results: Fifty-three questions and answers addressing lateral meniscal lesions were drafted, and 20 statements were excluded because of redundant information during the first round of voting. Ultimately, 33 statements were completed, 9 of which were unanimous. Conclusion: This expert consensus process focused on the anatomy, function, pathological processes, and treatment of lateral meniscal lesions. Accepted recommendations in these areas can assist doctors and therapists in standardizing the management of related pathology. The consensus statement indicates that certain types of lateral meniscal tears that were previously considered irreparable can be repaired. Preservation of the lateral meniscus should be the first-line treatment whenever possible, because the long-term clinical and radiological outcomes are worse after partial meniscectomy.

Surface modification of the simvastatin factor-loaded silk fibroin promotes the healing of rotator cuff injury through ß-catenin signaling.

Rupture of the rotator cuff is a common injury of the shoulder joint in sports professionals. In addition, research on repair of the rotator cuff has gained popularity over the recent years. Given the high rate of re-tear after surgery, it is necessary to design and prepare biodegradable materials with good mechanical properties, for the management of the condition. Consequently, the present study conducted surface modification of the simvastatin factor-loaded silk fibroin for the repair of chronic rotator cuff injury in SD rats. The in vitro experiments were analyzed through scanning electron microscopy and the water contact angle. Additionally, the CCK-8 assay was used to observe the effect of the intervention on the proliferation of BMSCs. Moreover, the osteogenic differentiation of BMSCs was detected through the ALP and ARS assays while the expression of osteogenic genes was examined using qRT-PCR and Western blot analysis. Furthermore, a model for repairing chronic rotator cuff tears in SD rats was established in vivo. Thereafter, rotator cuff repair and healing were evaluated through HE staining while Masson and Sirius staining was used to detect the collagen formation ratio. Additionally, the study analyzed the mechanism underlying the effect of simvastatin-loaded silk fibroin. The results showed that the simvastatin-loaded silk fibroin membrane had better biocompatibility and the in vitro experiments confirmed that it could promote the proliferation and osteogenic differentiation of BMSCs. In addition, the in vivo HE staining experiments similarly confirmed that it could enhance tendon bone healing and alleviate inflammation in chronic rotator cuff injuries. On the other hand, Masson and Sirius staining showed that the simvastatin-loaded silk fibroin could promote the formation of collagen. Further analysis also revealed that it could promote the osteogenic differentiation of BMSCs by activating the ß-catenin signaling pathway. In general, these findings suggested that surface modification of the simvastatin factor-loaded silk fibroin was a potential means of improving the healing of rotator cuff injuries and can be implemented in clinical practice in future.

Reduced expression of carbonic anhydrase III in skeletal muscles could be linked to muscle fatigue: A rat muscle fatigue model.

BACKGROUND: Carbonic anhydrase III (CAIII) is expressed abundantly in slow skeletal muscles, adipocytes, and the liver. It plays a critical role in maintaining intracellular pH, antioxidation, and energy metabolism, which are further involved in fatigue. However, its function and mechanism in maintaining the physiological function of muscles or antifatigue are still ambiguous. We hypothesized that changes of CAIII in skeletal muscles might be related to the occurrence of muscle fatigue. METHOD: After establishing a rat soleus muscle fatigue model, we measured the protein expression of the CAIII in muscles. And the muscle intracellular biochemical indices [malondialdehyde (MDA), adenosine triphosphate (ATP), and lactic acid] were also measured using assay kits. After transfected by CAIII-overexpressing and knockdown lentiviral vectors, the rat soleus muscles were induced to fatigue to investigate the effects and possible molecular mechanisms of CAIII in antifatigue. RESULTS: The expression of CAIII in fatigued soleus muscles was significantly decreased compared with that of the control group (P â€‹< â€‹0.001). Moreover, the ATP level in the fatigued muscle also significantly decreased, whereas lactic acid and MDA levels were significantly increased (P â€‹< â€‹0.001). After posttransfection for 21 days, CAIII levels in muscles were significantly reduced in the CAIII-interfering lentivirus group, but increased in the CAIII-overexpressed lentivirus group (P â€‹< â€‹0.001). In addition, CAIII knockdown muscles showed more reduction of the maximal muscle force and ATP levels â€‹and more increase of MDA and lactic acid levels during the fatigue test than the control group, (P â€‹< â€‹0.05). On the other hand, CAIII-overexpressed muscles showed less reduction of the maximal muscle force and ATP levels and less increase of MDA and lactic acid levels during muscle fatigue than the control group (P â€‹< â€‹0.05). CONCLUSIONS: Our study showed that soleus muscle fatigue induced by electrical stimulation could result in downregulation of CAIII and ATP levels â€‹and accumulation of lactic acid and MDA. Further study showed that CAIII knockdown led to more reduction of the maximal muscle force, whereas CAIII overexpression showed less reduction of the maximal muscle force, which suggested that CAIII levels in muscles might be related to the occurrence of muscle fatigue. TRANSLATIONAL POTENTIAL: CAIII plays an important role in muscle fatigue. Up-regulating the expression of CAIII might contribute to dissipating fatigue, which would provide a new method to solve the difficulties in eliminating muscular fatigue.

Carbonic anhydrase III: the new hope for the elimination of exercise-induced muscle fatigue.

Fatigue, defined as the failure to maintain the required or expected power output, is a complex problem. Its occurrence mechanism is extremely complicated. The obvious reasons are that it is a multifactorial situation and that the limiting factors may vary with force intensity, exercise duration and muscle type. In recent years, it has been found that carbonic anhydrase III(CAIII) which is present in high concentrations in muscles has multiple biological activities that can dissipate or resist some fatigue related substances. Therefore, we hypothesize that the CAIII supplementation may contribute to dissipate fatigue. Confirmation of this hypothesis will further add to our understanding of the physiological functions of CAIII and will be hopeful to solve the difficulties in eliminating muscular fatigue.