Agomir-122-loaded nanoparticles coated with cell membrane of activated fibroblasts to treat frozen shoulder based on homologous targeting.

As a common musculoskeletal disorder, frozen shoulder is characterized by thickened joint capsule and limited range of motion, affecting 2-5% of the general population and more than 20% of patients with diabetes mellitus. Pathologically, joint capsule fibrosis resulting from fibroblast activation is the key event. The activated fibroblasts are proliferative and contractive, producing excessive collagen. Albeit high prevalence, effective anti-fibrosis modalities, especially fibroblast-targeting therapies, are still lacking. In this study, microRNA-122 was first identified from sequencing data as a potential therapeutic agent to antagonize fibroblast activation. Then, Agomir-122, an analog of microRNA-122, was loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Agomir-122@NP), a carrier with excellent biocompatibility for the agent delivery. Moreover, relying on the homologous targeting effect, we coated Agomir-122@NP with the cell membrane derived from activated fibroblasts (Agomir-122@MNP), with an attempt to inhibit the proliferation, contraction, and collagen production of abnormally activated fibroblasts. After confirming the targeting effect of Agomir-122@MNP on activated fibroblasts in vitro, we proved that Agomir-122@MNP effectively curtailed fibroblasts activation, ameliorated joint capsule fibrosis, and restored range of motion in mouse models both prophylactically and therapeutically. Overall, an effective targeted delivery method was developed with promising translational value against frozen shoulder.

Ambient air pollution exposure and the risk of probable sarcopenia: A prospective cohort study.

BACKGROUND: Sarcopenia is characterized by decreased muscle mass and strength, posing threat to quality of life. Air pollutants are increasingly recognized as risk factors for diseases, while the relationship between the two remains to be elucidated. This study investigated whether exposure to ambient air pollution contributes to the development of sarcopenia. METHODS: We employed the data from the UK Biobank with 303,031 eligible participants. Concentrations of PM2·5, NO2, and NOx were estimated. Cox proportional hazard regression models were applied to investigate the associations between pollutants and sarcopenia. RESULTS: 30,766 probable sarcopenia cases was identified during the follow-up. We observed that exposure to PM2.5 (HR, 1.232; 95% CI, 1.053-1.440), NO2 (HR, 1.055; 95% CI, 1.032-1.078) and NOx (HR, 1.016; 95% CI, 1.007-1.026) were all significantly associated with increased risk for probable sarcopenia for each 10 µg/m3 increase in pollutant concentration. In comparison with individuals in the lowest quartiles of exposure, those in the upper quartiles had significantly increased risk of probable sarcopenia. Sarcopenia-related factors, e.g., reduced lean muscle mass, diminished walking pace, and elevated muscle fat infiltration ratio, also exhibited positive associations with exposure to ambient air pollution. On the contrary, high level physical activity significantly mitigated the influence of air pollutants on the development of probable sarcopenia. CONCLUSIONS: Air pollution exposure elevated the risk of developing sarcopenia and related manifestations in a dose-dependent manner, while physical activity maintained protective under this circumstance. Efforts should be made to control air pollution and emphasize the importance of physical activity for skeletal muscle health under this circumstance.

Anterior cruciate ligament femoral footprint is oblong-ovate, triangular, or two-tears shaped in healthy young adults: three-dimensional MRI analysis.

PURPOSE: This study aimed to evaluate the morphology of the anterior cruciate ligament (ACL) femoral footprint with three-dimensional magnetic resonance imaging (3D MRI) in healthy knees. METHODS: Fifty subjects with healthy knees were recruited, utilising 3D-SPACE sequences for ACL evaluation. The ACL was manually segmented, and the shape, size and location of the ACL femoral footprint were evaluated on a reformatted oblique-sagittal plane, which aligned closely with the ACL attachment. Statistical analysis included one-way ANOVA for continuous variables and Fisher's exact test for categorical variables, with a P value < 0.05 considered significant. RESULTS: Three types of ACL femoral footprint shape were identified, namely, oblong-ovate (OO) in 33 knees (66%), triangular (Tr) in 12 knees (24%) and two-tears (TT) in 5 knees (10%), with the mean areas being 58, 47 and 68 mm2, respectively. Within group TT, regions with similar sizes but different locations were identified: high tear (TT-H) and low tear (TT-L). Notably, group OO demonstrated a larger notch height index, whilst group TT was characterised by a larger α angle and lateral femoral condyle index. A noticeable variation was observed in the location of the femoral footprint centre across groups, with group TT-L and group Tr showing a more distal position relative to the apex of the deep cartilage. According to the Bernard and Hertel (BH) grid, the ACL femoral footprint centres in group TT-L exhibited a shallower and higher position than other groups. Furthermore, compared to group OO and TT-H, group Tr showed a significantly higher position according to the BH grid. CONCLUSION: In this study, the morphology of the ACL femoral footprint in healthy young adults was accurately evaluated using 3D MRI, revealing three distinct shapes: OO, Tr and TT. The different ACL femoral footprint types showed similar areas but markedly different locations. These findings emphasise the necessity of considering both the shape and precise location of the ACL femoral footprint during clinical assessments, which might help surgeons enhance patient-specific surgical plans before ACL reconstruction. LEVEL OF EVIDENCE: IV.

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.

Long non-coding RNA MFAT1 promotes skeletal muscle fibrosis by modulating the miR-135a-5p-Tgfbr2/Smad4 axis as a ceRNA.

Fibrosis after skeletal muscle injury is common in sports and can cause irreversible damage to the biomechanical properties of skeletal muscle. Long non-coding RNAs (lncRNAs) have been validated to act as important modulators in the fibrosis of various organs. Here, we reported a novel lncRNA (the skeletal muscle fibrosis-associated transcript 1, lnc-MFAT1), which was highly expressed in skeletal muscle fibrosis. We demonstrate that lnc-MFAT1 knockdown can reduce TGFß-induced fibrosis in vitro and attenuate skeletal muscle fibrosis after acute contusion in mice. Further study showed that lnc-MFAT1 acted as a competitive endogenous RNA of miR-135a-5p. Besides, the miR-135a-5p inhibition obviously promoted TGFß-induced fibrosis in vitro via enhancing its target genes Tgfbr2/Smad4. Moreover, we discovered that lnc-MFAT1 regulates Tgfbr2/Smad4 expression by sponging miR-135a-5p to exert competing endogenous RNA function, resulting in TGFß pathway activation. In conclusion, our study identified a crucial role of lnc-MFAT1-miR-135a-Tgfbr2/Smad4 axis in skeletal muscle fibrosis, providing a promising treatment option against skeletal muscle fibrosis.

Long non-coding RNA H19 promotes myoblast fibrogenesis via regulating the miR-20a-5p-Tgfbr2 axis.

Emerging evidence has indicated long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, including fibrosis. Here, we report that lncRNA H19 is able to promote skeletal muscle fibrosis. lnc-H19 was identified to be highly expressed in skeletal muscle fibrosis in vivo and in vitro; while lnc-H19 knockdown attenuated fibrosis in vitro. The knockdown of lnc-H19 was proved to inhibit the activation of the TGFß/Smad pathway in C2C12 myoblasts by sponging miR-20a-5p to regulate Tgfbr2 expression through the competing endogenous RNA function. Our study elucidates the roles of the lnc-H19-miR-20a-5p-Tgfbr2 axis in regulating the TGFß/Smad pathway of myoblast fibrogenesis, which might provide a promising therapeutic target for skeletal muscle fibrosis.

miR-122-5p negatively regulates the transforming growth factor-ß/Smad signaling pathway in skeletal muscle myogenesis.

Regeneration remains a major challenge in skeletal muscle repair after injury. Recently, transforming growth factor-ß (TGF-ß)/Smad pathway was found to play an important role in inhibiting myogenesis, a crucial stage in skeletal muscle regeneration. In our previous study, microRNA-122-5p (miR-122) was proved to have the function of downregulating TGF-ß/Smad pathway. Theoretically, miR-122 might also be involved in the process of skeletal muscle myogenesis through the regulation of TGF-ß/Smad pathway. In this study, we aimed to investigate the impact of miR-122 on skeletal muscle myogenesis and explore its underlying mechanism. Results showed that miR-122 and myogenic markers were downregulated in C2C12 cells after TGF-ß stimulation, and miR-122 overexpression could restore the myogenesis inhibited by TGF-ß. We then located TGFBR2 as the direct target of miR-122 and discovered the effect of miR-122 overexpression could be rescued by TGFBR2 overexpression. Further, the downstream molecules of TGFBR2 in the TGF-ß/Smad pathway were found to be suppressed by miR-122. In conclusion, miR-122 could suppress the TGF-ß/Smad signalling pathway by directly targeting TGFBR2 and, consequently, restore myogenesis. SIGNIFICANCE OF THE STUDY: Regeneration remains a major challenge in skeletal muscle repair after injury. In this study, it was found that miR-122 could suppress the TGF-ß/Smad signalling pathway by directly targeting TGFBR2 and, consequently, restore myogenesis. Our findings could inspire future experiments on the role of miRs in skeletal muscle diseases and future translational studies on potential novel gene therapy for skeletal muscle injury.

Editorial Commentary: Arthroscopy for Borderline Developmental Dysplasia of the Hip: Selection Determines the Outcomes.

Although the literature has presented results that favored arthroscopic procedures in treating borderline developmental dysplasia of the hip (BDDH), it remains controversial whether arthroscopic surgery would be better than periacetabular osteotomy for BDDH. Instead of a debate on the application of arthroscopy, the issue worthy of discussion should be distinguishing suitable BDDH candidates for hip arthroscopy. First, identification of patients with real BDDH is critical for making management choices. Second, it should be distinguished whether the major symptoms result from mechanical lesions or functional hip instability. Third, once hip arthroscopy is suggested for BDDH patients, relative contraindications such as advanced age and osteoarthritis should be taken into consideration, in addition to labral repair and capsular closure or plication intraoperatively. In conclusion, more long-term and high-grade evidence is still demanded to end the debate, but we believe that an individualized management strategy based on an accurate diagnosis and comprehensive assessment will bring optimal outcomes for BDDH patients.

The Encystment-Related MicroRNAs and Its Regulation Molecular Mechanism in Pseudourostyla cristata Revealed by High Throughput Small RNA Sequencing.

MicroRNAs (miRNAs) regulate the expression of target genes in diverse cellular processes and play important roles in different physiological processes. However, little is known about the microRNAome (miRNAome) during encystment of ciliated protozoa. In the current study, we first investigated the differentially expressed miRNAs and relative signaling pathways participating in the transformation of vegetative cells into dormant cysts of Pseudourostyla cristata (P. cristata). A total of 1608 known miRNAs were found in the two libraries. There were 165 miRNAs with 1217 target miRNAs. The total number of differential miRNAs screened between vegetative cells and dormant cysts databases were 449 with p < 0.05 and |log2 fold changes| > 1. Among them, the upregulated and downregulated miRNAs were 243 and 206, respectively. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that some of the differentially expressed miRNAs were mainly associated with oxidative phosphorylation, two-component system, and biosynthesis of amino acids. Combining with our bioinformatics analyzes, some differentially expressed miRNAs including miR-143, miR-23b-3p, miR-28, and miR-744-5p participates in the encystment of P. cristata. Based on these findings, we propose a hypothetical signaling network of miRNAs regulating or promoting P. cristata encystment. This study shed new lights on the regulatory mechanisms of miRNAs in encystment of ciliated protozoa.

Double-row rotator cuff repairs lead to more intensive pain during the early postoperative period but have a lower risk of residual pain than single-row repairs.

PURPOSE: The purpose of this study is to compare pain patterns and identify factors associated with residual shoulder pain after rotator cuff repairs using double-row and single-row techniques. METHODS: A cohort study was performed using patients who underwent arthroscopic rotator cuff repairs at our center in 2015. Patients were allocated according to the repair technique into an single-row (SR) group or a double-row (DR) group. Visual Analog Scale (VAS) scores for pain were assessed at 1 week, 3 months, 6 months, 12 months and 24 months after surgery. Functional and radiographic assessments were performed at least 24 months postoperatively. The proportion of patients with residual pain and factors associated with residual shoulder pain (VAS > 0 at the final follow-up) were analyzed in both groups. RESULTS: Fifty-two patients were enrolled in the SR group, and 53 were enrolled in the DR group. The DR group appeared to have higher levels of pain 1 week (P < 0.001) and 3 months (P = 0.041) postoperatively, while at other time points, the pain intensity of the two groups was comparable. Fourteen (26.4%) and 25 (48.1%) patients in the DR and the SR groups, respectively, developed residual shoulder pain, (P = 0.022; RR 1.82). The univariate analysis and multiple regression revealed that a poorer quality of tendon tissue is related to residual pain in the SR group, whereas tendon retraction is associated with residual pain in the DR group. The rate of re-tear was similar between the two groups and between patients with and without residual pain. CONCLUSIONS: The DR repair technique results in a greater intensity of pain than that of SR repair during the first 3 months after surgery; however, patients who underwent DR repair presented a significantly lower proportion of residual shoulder pain and better tendon quality after 2 years. Poorer tendon quality and larger tendon retraction as determined intraoperatively were risk factors for residual pain. These results highlight the necessity of promoting healing on the grounds of residual pain prevention. LEVEL OF EVIDENCE: II.

Time From Injury to Surgery Affects Graft Maturation Following Posterior Cruciate Ligament Reconstruction With Remnant Preservation: A Magnetic Resonance Imaging-Based Study.

PURPOSE: To evaluate the clinical outcomes and graft maturation following posterior cruciate ligament reconstruction (PCLR) with preserved remnant and further analyze the correlated factors affecting graft maturation. METHODS: Consecutive patients who underwent unilateral single-bundle PCLR with remnant preservation from January 2011 to October 2014 by the same senior doctor using tibialis anterior allografts and same surgical technique were included. At a follow-up of more than 2 years, range of motion (ROM) and posterior laxity assessed by posterior drawer test and the KT-1000 arthrometer were examined. Tegner, Lysholm, and International Knee Documentation Committee scores were evaluated. The graft maturation was assessed by a 3.0-T magnetic resonance imaging. Overall correlation analyses and multivariate regression analysis were performed to identify correlated factors of graft maturation, and then subgroups were divided and analyzed according to significant risk factor. RESULTS: Forty-three (84.3%) of 51 enrolled patients were successfully followed up (38.4 months, 24-54 months). All clinical scores improved significantly, and there were no complications. The results of KT-1000 difference revealed significant decline of posterior laxity (9.4 ± 1.5 vs 2.2 ± 1.5 mm; P < .001). The MRI evaluation confirmed no ligament retears. Both correlation and regression analyses showed time from injury to surgery had a positive, statistically significant weak correlation with the signal intensity score (R = 0.38, P = .012; coefficient = 0.10; P = .036). Subgroup (group 1: time from injury to surgery <3 months; group 2: 3-6 months; group 3: 6-12 months; group 4: ≥12 months) analysis showed there were no significant differences of clinical outcomes between subgroups, while MRI signal intensity was significantly lower in the group with shorter time from injury to surgery (P = .02). CONCLUSIONS: The remnant-preserved PCLR resulted in satisfactory clinical outcomes and graft maturation at a mean follow-up of 38.4 months. The time from injury to surgery showed a weak positive correlation with postoperative graft signal intensity on MRI. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

MRI-based tendon bone healing is related to the clinical functional scores at the first year after anterior cruciate ligament reconstruction with hamstring tendon autograft.

PURPOSE: The correlation between tendon bone healing and clinical functional scores after anterior cruciate ligament reconstruction (ACLR) using four-stranded hamstring tendon autograft has rarely being reported. The purpose of this study was to determine the correlation between magnetic resonance imaging (MRI)-based tendon bone healing and clinical functional scores after ACLR using hamstring tendon. METHODS: Thirty-eight patients with ACLR using four-stranded hamstring tendon autograft were included in this prospective study in the authors' hospital from 2013 to 2014. All patients were performed Tegner, Lysholm, International Knee Documentation Committee (IKDC) subjective scores, KT-1000 and MRI examinations in 3, 6, 12 months after the operation, respectively. According to MRI, the healing degree of tendon bone was divided into five grades, and the healing degree of the tendon at different time points was evaluated. Moreover, the correlations between the clinical scores and tendon bone healing level at 12 months after the operation were determined. RESULTS: The Tegner, Lysholm, and IKDC scores of all patients were gradually improved over time after ACLR, and the degree of tendon bone healing was gradually increased. Moreover, there were significantly positive correlations between the level of tendon bone healing and the clinical functional scores at 12 months after the operation. CONCLUSION: The clinical functional scores and the degree of tendon bone healing were gradually improved over time after ACLR. Moreover, there were significant positive correlations between the level of tendon bone healing and clinical functional scores of knee joint at the first year after the operation. LEVEL OF EVIDENCE: III.

miR-146a-5p acts as a negative regulator of TGF-ß signaling in skeletal muscle after acute contusion.

Growing evidence suggests the importance of microRNAs (miRNAs) in stress signaling pathways. Transforming growth factor-ß (TGF-ß) is a potent cytokine that promotes the development of skeletal muscle fibrosis after acute contusion. However, how miRNAs are involved in TGF-ß signaling and confer the robustness of TGF-ß-induced fibrotic response remains to be fully elucidated. Here, we demonstrated that miR-146a-5p (miR-146) levels were reduced in a fibrotic mouse model after acute muscle contusion. It was also found that TGF-ß treatment decreased the expression of miR-146 in vitro in a dose- and time-dependent manner. In addition, overexpression of Smad3 and Samd4, two key players in TGF-ß signaling, suppressed the expression of miR-146 in muscle cells. Overexpression of miR-146 inhibited the expressions of fibrosis markers both in vitro and in vivo. Moreover, increase in the expression of miR-146 in muscle cells was able to attenuate the effect of TGF-ß on the expressions of fibrosis markers. Mechanistic analysis revealed that Smad4 is a direct target of miR-146 in muscle cells. Furthermore, the anti-fibrotic effect of miR-146 could be blocked by overexpression of Smad4 in vivo. These results suggest that Smad4 is down-regulated by miR-146 in skeletal muscle. Taken together, our results indicate that the anti-fibrotic miR-146 is a component of TGF-ß signaling. It is down-regulated by Smad protein, and can inhibit the expression of Smad4. Our study suggests that miR-146 might have a therapeutic potential to reduce skeletal muscle fibrosis after injury.

MRI-based ACL graft maturity does not predict clinical and functional outcomes during the first year after ACL reconstruction.

PURPOSE: To determine whether magnetic resonance image (MRI)-based graft maturity predicts clinical and functional scores during the first year after ACL reconstruction. METHODS: Patients with unilateral ACL reconstruction were prospectively invited to participate in this study, and they were examined using a 3.0-T MRI scan at 3, 6, and 12 months after the operation. Clinical examinations were performed on the same day, including subjective functional examinations, physical examinations and the KT-1000 test. MRI measurements were focused on the graft signal intensity of the ACL graft using the signal/noise quotient value from a region of interest analysis. RESULTS: Finally, a total of 38 participants with ACL reconstruction were recruited for this study, including 21 with autograft tendons and 17 with allograft tendons. Generally, the signal/noise quotient values of the ACL grafts increased from 3 to 6 months and then decreased from 6 to 12 months. There was no significant association between graft signal/noise quotient value and IKDC, Lysholm, or Tegner scores at each time point. Graft signal/noise quotient value had a significant positive association with ATTD for the cohort (p = 0.002) and for the autograft group (p = 0.004) at 3 months. However, there was no significant association between graft signal/noise quotient value and ATTD at 6 or 12 months, respectively. CONCLUSION: The MRI-based graft maturity does not have the ability to predict clinical and functional outcomes in patients at the first-year follow-up. Graft maturity should not be used as an objective test to determine the appropriate time to return to sports during the first year after ACL reconstruction. The results from this study will allow clinicians to determine graft-specific health to determine whether the graft is healed enough to return to sports during the first postoperative year. LEVEL OF EVIDENCE: III.

Effect of centre-edge angle on clinical and quality of life outcomes after arthroscopic acetabular labral debridement.

PURPOSE: The aim of this study was to compare clinical and quality of life outcomes following arthroscopic acetabular labral debridement between patients with different centre-edge (CE) angle. METHODS: A total of 79 patients who underwent hip labral debridement were enrolled in this study. Radiographic measurements of CE angle were collected, and patients were assigned into a normal group (25° < CE angle <40°, n = 68) and dysplasia group (CE angle <20°, n = 11). Clinical outcomes were evaluated by modified Harris Hip Score (mHHS), Hip Outcome Score (HOS) for activities of daily living (ADL) and sports and Short Form 12 (SF-12). RESULTS: At the final follow-up, the normal group showed significant improvements in mHHS, HOS (ADL and sports) and SF-12 (P < 0.05). However, the dysplasia group revealed significant improvements in mHHS, HOS (ADL) and SF-12 physical component summary (PCS) (P < 0.05) and no significant changes in HOS sports and SF-12 mental component summary (MCS) (P > 0.05). Additionally, there was a greater improvement in clinical scores post-operatively in the normal group compared with the dysplasia group (P < 0.05). CONCLUSIONS: Arthroscopic acetabular labral debridement resulted in significantly greater clinical and quality of life outcomes in patients with CE angle >25° compared with patients with CE angle < 20°.

Comparison of tendon-bone healing between autografts and allografts after anterior cruciate ligament reconstruction using magnetic resonance imaging.

PURPOSE: The purpose of the study is to compare tendon-bone healing between autograft tendons and allograft tendons after anterior cruciate ligament (ACL) reconstruction using 3.0T magnetic resonance imaging. METHODS: A total of 36 participants (18 with autograft and 18 with allograft reconstruction) underwent MRI scans at least 2 years after the ACL reconstruction operation. Oblique axial images were obtained on three-dimensional dual-echo steady-state images and imported into solid modelling software for three-dimensional model reconstruction of the bone tunnel. The graft signal intensity in the tunnel, tendon-bone interface, tunnel morphology, and tunnel area was analysed using the Siemens software packages to determine the tendon-bone healing between the groups. RESULTS: For the tunnel morphology, both groups exhibited bone tunnel enlargement either at the femoral or tibial tunnel aperture. For the tendon-bone interface, one patient in the autograft group and two patients in the allograft group exhibited a significant fibrous scar tissue bands at the tendon-bone interface. The graft signal/noise quotient values of the allograft group were higher than the autograft group. However, there was no significant difference in the tunnel area between the allograft group and the autograft group. CONCLUSIONS: Although the autograft tendons exhibited a better remodelling effect than did the allograft tendons in the bone tunnel, there was no significant difference in the tendon-bone healing between the autograft tendons and the allograft tendons postoperatively. These findings indicate that the biomechanical effect of graft motion may play a significant role in the tunnel aperture. LEVEL OF EVIDENCE: III.

Outcome comparison of meniscal allograft transplantation (MAT) and meniscal scaffold implantation (MSI): A systematic review.

BACKGROUND: Although numerous studies have reported successful clinical outcomes of Meniscal allograft transplantation (MAT) or Meniscal scaffold implantation (MSI), the difference between the outcome of MAT and MSI remains unclear. PURPOSE: To compare the overall outcomes and survival rates of MAT and MSI, aiming to provide comprehensive evidence for determining the optimal treatment strategy for meniscal defects. METHODS: A systematic review was performed via a comprehensive search of PubMed, Embase, and the Cochrane Library. Studies of MAT or MSI were included according to the inclusion and exclusion criteria. The Lysholm score was chosen as the primary outcome measure, while secondary outcomes encompassed Patient-reported Outcome Measures (PROMs), Return to Sports (RTS) rates, survival rates, and complication rates. The outcomes were stratified into two groups: MAT group and MSI group, followed by statistical comparison (P<0.05). The quality of the included studies was assessed by the Cochrane Risk of Bias 2 (RoB2) assessment tool for randomized controlled trials (RCTs) and the Coleman Methodology Score (CMS) for non-randomized controlled trials. RESULTS: A total of 3932 patients (2859 MAT, 1073 MSI) in 83 studies (51 MAT, 32 MSI) had the overall significant improvement in all clinical scores. The group MSI had higher Lysholm score of both preoperative (P=0.002) and postoperative (P<0.001) than group MAT; however, the mean improvements were similar between the two groups (P=0.105). Additionally, MSI had higher improvements of IKDC (P<0.001), KOOS symptom (P=0.010), KOOS pain (P=0.036), and KOOS ADL (P=0.004) than MAT. Interestingly, MAT had higher preoperative (P=0.018) and less postoperative VAS pain (P=0.006), which was more improved in MAT (P<0.001). Compared with MAT, MSI had higher 10-year survival rate (P=0.034), similar mid-term survival rate MAT (P=0.964), and lower complication rate (P<0.001). CONCLUSION: Both MAT and MSI could have good clinical outcomes after surgery with the similar improvement in Lysholm score. MSI had higher 10-year survival rate and less complications than MAT. LEVEL OF EVIDENCE: IV, systematic review.

Early Weight-bearing Rehabilitation Protocol After Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament (ACL) injury is one of the common sports injuries. Anterior cruciate ligament reconstruction (ACLR) is the mainstream treatment for ACL injury, aiming to regain normal anatomical structure and stability of the knee joint and promote the patient's return to sports. Under the guidance of the concept of enhanced recovery after surgery, early weight-bearing rehabilitation (EWB) is an important factor affecting patient function and quality of life. However, there is no consensus on whether EWB rehabilitation can be performed after ACL surgery. This study aims to explore the safety and feasibility of EWB after ACL surgery. The study implemented a gradual EWB rehabilitation program in the experimental group, including weight-shifting training, balance training, and gait training on the affected lower limb, and assessed wound healing and stability of the knee joint. The study found that EWB after ACLR is safe and feasible. EWB rehabilitation not only does not pose a negative effect on the patient's knee pain, swelling, wound healing, and stability, but also helps to improve knee active flexion and quality of life faster and better. The EWB program in this study is simple, safe, and effective, and it provides strong theoretical guidance and practical demonstration for accelerated rehabilitation after ACLR.

Macrophage-Myofibroblast Transition as a Potential Origin for Skeletal Muscle Fibrosis After Injury via Complement System Activation.

Background: Acute skeletal muscle injury is common in sports. The injured muscle cannot fully recover due to fibrosis resulting from myofibroblasts. Understanding the origin of fibroblasts is, therefore, important for the development of anti-fibrotic therapies. Accumulating evidence shows that a mechanism called macrophage-myofibroblast transition (MMT) can lead to tissue or organ fibrosis, yet it is still unclear whether MMT exists in skeletal muscle and the exact mechanisms. Methods: Single-cell transcriptome of mice skeletal muscle after acute injury was analyzed with a specific attention on the process of MMT. Cell-cell interaction network, pseudotime trajectory analysis, Gene Ontology (GO), and Kyoto Genome Encyclopedia (KEGG) were conducted. A series of experiments in vivo and in vitro were launched for verification. Results: Single cell transcriptomic analysis indicated that, following acute injury, there were much interactions between macrophages and myofibroblasts. A detailed analysis on macrophages indicated that, CD68+α-SMA+ cells, which represented the status of MMT, mainly appeared at five days post-injury. KEGG/GO analysis underlined the involvement of complement system, within which C3ar1, C1qa, C1qb, and C1qc were up-regulated. Trajectory analysis also confirmed a potential shift from macrophages to myofibroblasts. These findings were verified by histological study in mice skeletal muscle, that there were much MMT cells at five days, declined gradually, and vanished 14 days after trauma, when there was remarkable fibrosis formation within the injured muscle. Moreover, C3a stimulation could directly induce MMT in BMDMs. Conclusion: Fibrosis following acute injury is disastrous to skeletal muscle, but the origin of myofibroblasts remains unclear. We proved that, following acute injury, macrophage-myofibroblast transition happened in skeletal muscle, which may contribute to fibrosis formation. This phenomenon mainly occurred at five days post-injury. The complement system can activate MMT. More evidence is needed to directly support the pro-fibrotic role of MMT in skeletal muscle fibrosis after acute injury.

Shape-Persistent Conductive Nerve Guidance Conduits for Peripheral Nerve Regeneration.

To solve the problems of slow regeneration and mismatch of axon regeneration after peripheral nerve injury, nerve guidance conduits (NGCs) have been widely used to promote nerve regeneration. Multichannel NGCs have been widely studied to mimic the structure of natural nerve bundles. However, multichannel conduits are prone to structural instability. Thermo-responsive shape memory polymers (SMPs) can maintain a persistent initial structure over the body temperature range. Electrical stimulation (ES), utilized within nerve NGCs, serves as a biological signal to expedite damaged nerve regeneration. Here, an electrospun shape-persistent conductive NGC is designed to maintain the persistent tubular structure in the physiological temperature range and improve the conductivity. The physicochemical and biocompatibility of these P, P/G, P/G-GO, and P/G-RGO NGCs are conducted in vitro. Meanwhile, to evaluate biocompatibility and peripheral nerve regeneration, NGCs are implanted in subcutaneous parts of the back of rats and sciatic nerves assessed by histology and immunofluorescence analyses. The conductive NGC displays a stable structure, good biocompatibility, and promoted nerve regeneration. Collectively, the shape-persistent conductive NGC (P/G-RGO) is expected to promote peripheral nerve recovery, especially for long-gap and large-diameter nerves.