Publications by authors named "Kanglai Tang"

76 Publications

Comprehensive Analysis of the Effects of Genetic Ancestry and Genetic Characteristics on the Clinical Evolution of Oral Squamous Cell Carcinoma.

Front Cell Dev Biol 2021 7;9:678464. Epub 2021 Dec 7.

Department of Stomatology, The 970th Hospital of the Joint Logistics Support Force, Yantai, China.

Oral squamous cell carcinoma (OSCC), a kind of malignant cancer, is associated with increasing morbidity and mortality. Patients with different genetic ancestries may respond differently to clinical treatment. The limited understanding of the influence of genetic ancestry and genetic characteristics on OSCC impedes the development of precision medicine. To provide a reference for clinical treatment, this study comprehensively analyzed multigenomic differences in OSCC patients with different genetic ancestries and their impact on prognosis. An analysis of data from OSCC patients with different genetic ancestries in The Cancer Genome Atlas (TCGA) showed that the overall survival (OS) of African (AFR) patients was lower than that of primarily European (EUR) patients, and differences were also observed in the tumor-stroma ratio (TSR) and tumor-infiltrating lymphocytes (TILs), which are associated with prognosis. is a key mutant gene in OSCC, and it has inconsistent effects on clinical evolution for patients with diverse genetic characteristics. and showed a significant difference in mutation frequency between EUR and AFR; was related to Ki-67 expression, suggesting that it could promote tumor proliferation, and was related to the expression of Bcl-2, promoting tumor cell apoptosis. A variant methylation locus, cg20469139, was correlated with the levels of PD-L1 and Caspase-7 and modulated tumor cell apoptosis. A novel ceRNA model was constructed based on genetic ancestries, and it could accurately evaluate patient prognosis. More importantly, although T cell dysfunction scores could determine the potential of tumor immune escape, the efficacy was obviously affected by patients' genetic ancestries. To provide patients with more precise, personalized therapy and to further improve their quality of life and 5-year survival rate, the influence of genetic ancestry should be fully considered when selecting treatments.
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http://dx.doi.org/10.3389/fcell.2021.678464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689072PMC
December 2021

Effects of aging on the histology and biochemistry of rat tendon healing.

BMC Musculoskelet Disord 2021 Nov 15;22(1):949. Epub 2021 Nov 15.

Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing, 400038, China.

Introduction: Tendon diseases and injuries are a serious problem for the aged population, often leading to pain, disability and a significant decline in quality of life. The purpose of this study was to determine the influence of aging on biochemistry and histology during tendon healing and to provide a new strategy for improving tendon healing.

Method: A total of 24 Sprague-Dawley rats were equally divided into a young and an aged group. A rat patellar tendon defect model was used in this study. Tendon samples were collected at weeks 2 and 4, and hematoxylin-eosin, alcian blue and immunofluorescence staining were performed for histological analysis. Meanwhile, reverse transcription-polymerase chain reaction (RT-PCR) and western blot were performed to evaluate the biochemical changes.

Results: The histological scores in aged rats were significantly lower than those in young rats. At the protein level, collagen synthesis-related markers Col-3, Matrix metalloproteinase-1 and Metallopeptidase Inhibitor 1(TIMP-1) were decreased at week 4 in aged rats compared with those of young rats. Though there was a decrease in the expression of the chondrogenic marker aggrecan at the protein level in aged tendon, the Micro-CT results from weeks 4 samples showed no significant difference(p>0.05) on the ectopic ossification between groups. Moreover, we found more adipocytes accumulated in the aged tendon defect with the Oil Red O staining and at the gene and protein levels the markers related to adipogenic differentiation.

Conclusions: Our findings indicate that tendon healing is impaired in aged rats and is characterized by a significantly lower histological score, decreased collagen synthesis and more adipocyte accumulation in patellar tendon after repair.
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http://dx.doi.org/10.1186/s12891-021-04838-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594129PMC
November 2021

[The short-term effectiveness of superior capsular reconstruction using autologous fascia lata graft for irreparable massive rotator cuff tears].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Nov;35(11):1427-1433

Department of Orthopedics/Sports Medicine Center, the First Affiliated Hospital of the Army Military Medical University, Chongqing, 400038, P.R.China.

Objective: To observe and evaluate the short-term effectiveness of superior capsular reconstruction using autologous fascia lata graft for irreparable massive rotator cuff tears.

Methods: The clinical data of 9 patients with irreparable massive rotator cuff tears treated with arthroscopic superior capsular reconstruction by using autologous fascia lata graft between September 2019 and April 2020 were retrospectively analysed. There were 4 males and 5 females with a median age of 66 years (range, 55-70 years). The disease duration was 6-60 months with an average of 19.1 months. According to Hamada classification, the patients were classified as grade 1 in 2 cases, grade 2 in 2 cases, grade 3 in 2 cases, and grade 4 in 3 cases. Before and after operation, the visual analogue scale (VAS) score was used to evaluate the improvement of shoulder joint pain, the American Shoulder and Elbow Surgeons (ASES) score, Constant score, and the University of California Los Angeles (UCLA) shoulder function score were used to evaluate the improvement of shoulder joint function. The active range of motion of shoulder joint was recorded, including forward flexion, abduction, lateral external rotation, and internal rotation. The changes of subacromial space were recorded by anteroposterior X-ray film of shoulder joint. Sugaya classification was used to judge the integrity of rotator cuff immediately after operation and at last follow-up.

Results: The operation time was 210-380 minutes, with an average of 302.3 minutes. All incisions healed by first intention after operation, and there was no complication such as infection and nonunion of incisions. Two patients had numbness of the upper limbs on the surgical side after operation, and the numbness completely relieved at 6 weeks after operation; 5 cases with preoperative pseudoparalysis symptoms recovered after operation. Nine patients were followed up 12-17 months, with an average of 14.1 months. At last follow-up, the patient's active range of motion of shoulder joint (forward flexion, abduction, lateral external rotation, and internal rotation), subacromial space distance, VAS score, ASES score, Constant score, and UCLA score significantly improved when compared with preoperative ones ( <0.05). There was no significant difference in the Sugaya classification between at last follow-up and immediately after operation ( =-1.633, =0.102).

Conclusion: Superior capsular reconstruction using autologous fascia lata graft can restore the superior stability and achieve a good short-term effectiveness for irreparable massive rotator cuff tears.
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http://dx.doi.org/10.7507/1002-1892.202104003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586772PMC
November 2021

Advancement in Arthroscopic Superior Capsular Reconstruction for Irreparable Massive Rotator Cuff Tear.

Orthop Surg 2021 Oct 29;13(7):1951-1959. Epub 2021 Sep 29.

Department of Orthopedic Surgery, Southwest Hospital, Army Military Medical University, Chongqing, China.

Irreparable massive rotator cuff tear (IMRCT) was one of the causes of shoulder dysfunction, despite technical improvement, the failure rate of IMRCT was still demonstrated to be high. Traditional treatments like non-surgical treatments, partial rotator cuff repair, and tendon transfers could only achieve a slight improvement. A potential cause for high failure rate was the fact that traditional treatments cannot restore the superior stability of glenohumeral joint, and thus restricted the movement of shoulder joint severely. Superior capsular reconstruction (SCR) using a variety of grafts (autograft, allograft, xenograft, or synthetic grafts) provided a promising option for IMRCT. In surgery, graft was fixed medially to superior glenoid and laterally to the footprint of humeral greater tuberosity. SCR could increase the stability of the superior glenohumeral joint, decrease the subacromial pressure and acromiohumeral distance. This review summarized the relevant literature regarding the alternative grafts, surgery indications, operative techniques and clinical outcomes of SCR. we compared the different grafts, key surgical steps, the advantages and disadvantages of different surgical methods to provide clinicians with new surgical insights into the treatments of IMRCT. In conclusion, IMRCT without severe glenohumeral arthritis was the best suitable indication for SCR. The clinical outcomes were positive in the short-term and middle-term following-up. More studies were necessary to determine long-term results of this surgical procedure.
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http://dx.doi.org/10.1111/os.12976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528972PMC
October 2021

Femtosecond laser-induced periodic grooves and nanopore clusters make a synergistic effect on osteogenic differentiation.

Colloids Surf B Biointerfaces 2021 Dec 4;208:112021. Epub 2021 Aug 4.

Department of Orthopedics/Sports Medicine Center, The First Affiliated Hospital of Army Medical University of Chinese PLA, Chongqing, 400038, PR China. Electronic address:

Polyether-ether-ketone (PEEK) materials have good biocompatibility, excellent corrosion resistance, chemical stability and an elastic modulus close to that of natural bone. However, due to its biological inertness, PEEK may affect osteogenic differentiation and leads to osseointegration failure, though PEEK is expected to improve osseointegration. In this work, by changing the power of femtosecond laser, micro-grooves are made on the PEEK surface. As observed by scanning electron microscopy, the trench has a periodic structure, the micro shape is neat, and the trench is also covered with nanometer-level pore clusters. In the in vitro culture experiments, through the proliferation experiment of mouse bone marrow mesenchymalstem cells (mBMSCs), cell viability analysis and alkaline phosphatase activity analysis, it is proven that after femtosecond laser treatment of the PEEK surface, the micro-grooves on the surface and the nanopore clusters due to laser energy ablation can produce a synergistic effect, enhancing the osteogenic differentiation ability of cells, and improving the bone integration ability of PEEK materials.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112021DOI Listing
December 2021

Corrigendum to "Bionic Silk Fibroin Film Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells by Activating Focal Adhesion Kinase".

Stem Cells Int 2021 2;2021:6317062. Epub 2021 Mar 2.

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China.

[This corrects the article DOI: 10.1155/2020/8857380.].
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http://dx.doi.org/10.1155/2021/6317062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946452PMC
March 2021

[Research progress of indication and treatment of graft in shoulder superior capsular reconstruction for rotator cuff tear].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Feb;35(2):252-257

Department of Sports Medicine, the First Affiliated Hospital of the Army Military Medical University, Chongqing, 400038, P.R.China.

Objective: To review the research progress of indication and treatment of graft in shoulder superior capsular reconstruction (SCR) for rotator cuff tear (RCT).

Methods: The literature related to shoulder SCR in recent years was extensively reviewed, and the anatomy, biomechanics, surgical indications, and treatment of graft in SCR were summarized.

Results: Superior capsule plays a role as a functional complex with rotator cuff, ligament, and whole capsule. SCR can effectively restore the superior stability of the shoulder. The indications of SCR include the irreparable massive RCT, massive RCT combined with pseudoparalysis shoulder, medium/large RCT with severe degenerative rotator cuff tissue, and dual-layer RCT. In order to achieve a better healing of tendon-bone in graft and decrease the rate of long-term graft retearing, it is essential to select an appropriate thickness graft, fix the graft in right intensity, and get a better capsular continuity.

Conclusion: The technique of SCR advanced to SCR for reinforcement and it is indicated from substantial massive RCT to severe degeneration of rotator cuff tissue. Graft treatment is the key step for a successful SCR.
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http://dx.doi.org/10.7507/1002-1892.202006015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171687PMC
February 2021

[Anatomical reconstruction of anterior talofibular ligament by partial peroneal brevis tendon combined with double intra-fix screws].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jan;35(1):70-75

Sports Medicine Center, the First Affiliated Hospital of Army Medical University, Chongqing, 400038, P.R.China.

Objective: To investigate the effectiveness of anatomical reconstruction of the anterior talofibular ligament by partial peroneal brevis tendon combined with double intra-fix screws.

Methods: A clinical data of 46 patients with the anterior talofibular ligament rupture admitted between September 2015 and October 2019 and met the selection criteria were retrospectively analyzed. All anterior talofibular ligaments were reconstructed with partial peroneal brevis tendon and fixed with double intra-fix screws. There were 22 males and 24 females, with an average age of 28.1 years (range, 16-52 years). Forty cases had a history of ankle sprain, 1 case was injured by a heavy object, and 5 cases were suffered from falls. There were 17 cases on the left side and 29 cases on the right side. The disease duration ranged from 3 months to 10 years (median, 20.3 months). The visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, varus angle of ankle, and the difference of the anterior talar translation between healthy and affected sides (looseness, similarity, tightness) were recorded before and after operation; 23 patients were evaluated by Patient-Reported Outcomes Measurement Information System (PROMIS) score, including pain interference (PI) and physical function (PF) scores.

Results: The operation time was 39-179 minutes, with an average of 65.8 minutes. All incisions healed by first intention. All patients were followed up 12-30 months (mean, 23 months). The VAS score, AOFAS ankle-hindfoot score, varus angle of ankle, difference of the anterior talar translation between healthy and affected sides, and PI and PF scores of PROMIS at 6 months and last follow-up significantly improved when compared with those before operation ( <0.05). There was no significant difference in VAS score, PI score of PROMIS, and AOFAS ankle-hindfoot score between at 6 months and at last follow-up ( >0.05). However, the PF score of PROMIS, the difference of the anterior talar translation between healthy and affected sides, and the varus angle of ankle were significant ( <0.05).

Conclusion: Anatomical reconstruction of the anterior talofibular ligament by partial peroneal brevis tendon and double intra-fix screws has the advantages of small incision, convenient tendon removal, and firm graft fixation. The postoperative patients recover quickly and the effectiveness is satisfactory.
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http://dx.doi.org/10.7507/1002-1892.202007131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171602PMC
January 2021

[Research progress of treatment for massive rotator cuff tears].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jan;35(1):8-13

Department of Sports Medicine Center, the First Affiliated Hospital of the Army Medical University of Chinese PLA, Chongqing, 400038, P.R.China.

Objective: To review the research progress of treatment for massive rotator cuff tears.

Methods: The domestic and foreign literature about the treatment of massive rotator cuff tears was reviewed. The methods and effectiveness were extensively summarized.

Results: The treatment of massive rotator cuff tears still needs long-term research to promote its continuous improvement. The main goal of treatment is to relieve the symptoms and improve the shoulder joint function. With the development of arthroscopic technique, arthroscopic repair of rotator cuff tears has become a mature surgical protocol. Among these techniques, superior capsule reconstruction and patch augmentation for massive rotator cuff tears acquire more attention in recent years. As for rotator cuff arthropathy, reverse shoulder arthroplasty is considered to be a final choice.

Conclusion: Surgical treatment is the main choice for massive rotator cuff tears. Patients' age and muscle condition should be taken into consideration to decide the surgical technique.
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http://dx.doi.org/10.7507/1002-1892.202004056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171597PMC
January 2021

Bionic Silk Fibroin Film Induces Morphological Changes and Differentiation of Tendon Stem/Progenitor Cells.

Appl Bionics Biomech 2020 1;2020:8865841. Epub 2020 Dec 1.

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China.

Purpose: Tendon injuries are common musculoskeletal system disorders, but the ability for tendon regeneration is limited. Silk fibroin (SF) film may be suitable for tendon regeneration due to its excellent biocompatibility and physical properties. This study is aimed at evaluating the application value of bionic SF film in tendon regeneration.

Methods: Tendon stem/progenitor cells (TSPCs) were isolated from rat Achilles tendon and characterized based on their surface marker expression and multilineage differentiation potential. SF films with smooth or bionic microstructure surfaces (5, 10, 15, 20 m) were prepared. The morphology and mechanical properties of natural tendons and SF films were characterized. TSPCs were used as the seed cells, and the cell viability and cell adhesion morphology were analyzed. The tendongenesis-related gene expression of TSPCs was also evaluated using quantitative polymerase chain reaction.

Results: Compared to the native tendon, only the 10, 15, and 20 m SF film groups had comparable maximum loading and ultimate stress, with the exception of the breaking elongation rate. The 10 m SF film group had the highest percentage of oriented cells and the most significant changes in cell morphology. The most significant upregulations in the expression of , , and were also observed in the 10 m SF film group.

Conclusion: SF film with a bionic microstructure can serve as a tissue engineering scaffold and provide biophysical cues for the use of TSPCs to achieve proper cellular adherence arrangement and morphology as well as promote the tenogenic differentiation of TSPCs, making it a valuable customizable biomaterial for future applications in tendon repair.
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http://dx.doi.org/10.1155/2020/8865841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725557PMC
December 2020

Bionic Silk Fibroin Film Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells by Activating Focal Adhesion Kinase.

Stem Cells Int 2020 4;2020:8857380. Epub 2020 Nov 4.

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China.

Background: Tendon injuries are common musculoskeletal disorders in clinic. Due to the limited regeneration ability of tendons, tissue engineering technology is often used as an effective approach to treat tendon injuries. Silk fibroin (SF) films have excellent biological activities and physical properties, which is suitable for tendon regeneration. The present study is aimed at preparing a SF film with a bionic microstructure and investigating its biological effects.

Methods: A SF film with a smooth surface or bionic microstructure was prepared. After seeding tendon stem/progenitor cells (TSPCs) on the surface, the cell morphology, the expression level of tenogenic genes and proteins, and the focal adhesion kinase (FAK) activation were measured to evaluate the biological effect of SF films.

Results: The TSPCs on SF films with a bionic microstructure exhibited a slender cell morphology, promoted the expression of tenogenic genes and proteins, such as SCX, TNC, TNMD, and COLIA1, and activated FAK. FAK inhibitors blocked the enhanced expression of tenogenic genes and proteins.

Conclusion: SF films with a bionic microstructure may serve as a scaffold, provide biophysical cues to alter the cellular adherence arrangement and cell morphology, and enhance the tenogenic gene and protein expression in TSPCs. FAK activation plays a key role during this biological response process.
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http://dx.doi.org/10.1155/2020/8857380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657703PMC
November 2020

[Short-term effectiveness of arthroscopically capsular vertical mattress suturing for shoulder recurrent anterior dislocation combined with joint laxity].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Nov;34(11):1392-1398

Sports Medicine Center, the First Affiliated Hospital, Army Military Medical University, Chongqing, 400038, P.R.China.

Objective: To evaluate the short-term effectiveness of arthroscopically capsular vertical mattress suturing for shoulder recurrent anterior dislocation combined with joint laxity.

Methods: A retrospective analysis was performed on 6 shoulder recurrent anterior dislocation patients combined with joint laxity treated with arthroscopically capsular vertical mattress suturing between January 2017 and December 2018. There were 5 males and 1 female with an average age of 20.8 years (range, 19-24 years). The number of shoulder dislocation was 3-18 times, with an average of 9.5 times. The disease duration ranged from 2 to 60 months, with an average of 25.3 months. The preoperative Beighton score was 4-7, with an average of 5.8; the Instability Severity Index Score (ISIS) was 2-5, with an average of 3.5. There were 5 cases of simple Bankart injury and 1 case of bony Bankart injury. The range of motion of shoulder joint (including active flexion and lifting, external rotation, abduction and external rotation, and internal ratation) was recorded before operation and at last follow-up; Oxford shoulder instability score, Rowe shoulder instability score, and Simple Shoulder Test (SST) score were used to evaluate shoulder joint function before operation, at 6 months after operation, and at last follow-up, and complications were recorded.

Results: All patients were followed up 16-28 months (mean, 19.3 months). During the follow-up, all patients had satisfactory motor function, and no re-dislocation and postoperative neurovascular complications occurred. At last follow-up, the activities of active external rotation and abduction and external rotation were significantly improved when compared with those before operation ( <0.05); the activities of active flexion and lifting and internal rotation were not limited before and after operation, and the difference was not significant ( >0.05). The Oxford shoulder instability score, Rowe shoulder instability score, and SST score at 6 months after operation and at last follow-up were significantly improved when compared with those before operation ( <0.05); there was no significant difference between at 6 months after operation and at last follow-up ( >0.05).

Conclusion: The treatment of shoulder recurrent anterior dislocation combined with joint laxity by arthroscopically vertical matress suturing can achieve good short-term effectiveness.
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http://dx.doi.org/10.7507/1002-1892.202005030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171704PMC
November 2020

[Three-dimensional printed Ti6Al4V-4Cu alloy promotes osteogenic gene expression through bone immune regulation].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Sep;34(9):1170-1176

Department of Orthopedics, the First Affiliated Hospital of Army Medical University of Chinese PLA, Chongqing, 400038, P.R.China.

Objective: To investigate the effects of three-dimensional (3D) printed Ti6Al4V-4Cu alloy on inflammation and osteogenic gene expression in mouse bone marrow mesenchymal stem cells (BMSCs) and mouse mononuclear macrophage line RAW264.7.

Methods: Ti6Al4V and Ti6Al4V-4Cu alloys were prepared by selective laser melting, and the extracts of the two materials were prepared according to the biological evaluation standard of medical devices. The effects of two kinds of extracts on the proliferation of mouse BMSCs and mouse RAW264.7 cells were detected by cell counting kit 8 method. After co-cultured with mouse BMSCs for 3 days, the expression of osteogenesis- related genes [collagen type Ⅰ (Col-Ⅰ), alkaline phosphatase (ALP), Runx family transcription factor 2 (Runx-2), osteoprotegerin (OPG), and osteopontin (OPN)] were detected by real-time fluorescence quantitative PCR. After co-cultured with mouse RAW264.7 cells for 1 day, the expressions of inflammation-related genes [interleukin 4 (IL-4) and nitric oxide synthase 2 (iNOS)] were detected by real-time fluorescence quantitative PCR, and the supernatants of the two groups were collected to detect the secretion of vascular endothelial growth factor a (VEGF-a) and bone morphogenetic protein 2 (BMP-2) by ELISA. The osteogenic conditioned medium were prepared with the supernatants of the two groups and co-cultured with BMSCs for 3 days. The expressions of osteogenesis-related genes (Col-Ⅰ, ALP, Runx-2, OPG, and OPN) were detected by real-time fluorescence quantitative PCR.

Results: Compared with Ti6Al4V alloy extract, Ti6Al4V-4Cu alloy extract had no obvious effect on the proliferation of BMSCs and RAW264.7 cells, but it could promote the expression of OPG mRNA in BMSCs, reduce the expression of iNOS mRNA in RAW264.7 cells, and promote the expression of IL-4 mRNA. It could also promote the secretions of VEGF-a and BMP-2 in RAW264.7 cells. Ti6Al4V-4Cu osteogenic conditioned medium could promote the expressions of Col-Ⅰ, ALP, Runx-2, OPG, and OPN mRNAs in BMSCs. The differences were all significant ( <0.05).

Conclusion: 3D printed Ti6Al4V-4Cu alloy can promote RAW264.7 cells to secret VEGF-a and BMP-2 by releasing copper ions, thus promoting osteogenesis through bone immune regulation, which lays a theoretical foundation for the application of metal prosthesis.
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http://dx.doi.org/10.7507/1002-1892.201912139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171737PMC
September 2020

The absence of oestrogen receptor beta disturbs collagen I type deposition during Achilles tendon healing by regulating the IRF5-CCL3 axis.

J Cell Mol Med 2020 09 10;24(17):9925-9935. Epub 2020 Aug 10.

Department of Orthopedic Surgery, Southwest Hospital, Army Medical University, Chongqing, China.

Achilles tendon healing (ATH) remains an unanswered question in the field of sports medicine because it does not produce tissue with homology to the previously uninjured tissue. Oestrogen receptor β (ERβ) is involved in the injury and repair processes of tendons. Our previous study confirmed that ERβ plays a role in the early stage of ATH by affecting adipogenesis, but its role in extracellular matrix (ECM) remodelling is unknown. We established a 4-week Achilles tendon repair model to investigate the mechanism through which ERβ affects ATH at the very beginning of ECM remodelling phase. In vitro studies were performed using tendon-derived stem cells (TDSCs) due to their promising role in tendon healing. Behavioural and biomechanical tests revealed that ERβ-deficient mice exhibit weaker mobility and inferior biomechanical properties, and immunofluorescence staining and qRT-PCR showed that these mice exhibited an erroneous ECM composition, as mainly characterized by decreased collagen type I (Col I) deposition. The changes in gene expression profiles between ERβ-knockout and WT mice at 1 week were analysed by RNA sequencing to identify factors affecting Col I deposition. The results highlighted the IRF5-CCL3 axis, and this finding was verified with CCL3-treated TDSCs. These findings revealed that ERβ regulates Col I deposition during ATH via the IRF5-CCL3 axis.
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http://dx.doi.org/10.1111/jcmm.15592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520326PMC
September 2020

[Mid-term effectiveness of manipulation under anesthesia combined with arthroscopic capsular release and subacromial debridement for primary frozen shoulder].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Jun;34(6):737-743

Department of Orthopaedics/Sports Medicine Center, the First Affiliated Hospital of the Army Medical University of Chinese PLA, Chongqing, 400038, P.R.China.

Objective: To evaluate mid-term effectiveness of manipulation under anesthesia combined with arthroscopic capsular release and subacromial debridement for primary frozen shoulder.

Methods: Between January 2013 and December 2017, 33 patients of primary frozen shoulder were treated with manipulation under anesthesia combined with 360° arthroscopic capsular release and subacromial debridement. There were 10 males and 23 females, aged from 37 to 65 years, with a mean age of 50.9 years. The affected shoulder on left side in 17 cases and on right side in 16 cases. The disease duration was 6-13 months (mean, 8.4 months). Before and after operation, the visual analogue scale (VAS) score was used to evaluate the shoulder joint pain, Constant score was used to evaluate the shoulder joint function, and the flexion, abduction, and external rotation of shoulder joint were recorded. The internal rotation function was assessed based on the vertebral plane that the thumb could reach after internal rotation of the affected shoulder joint (the rank of internal rotation vertebra). X-ray film was taken to measure the distance of the subacromial space.

Results: There was no fracture or labrum tear in all patients, and all the incisions healed by first intention. All the 33 patients were followed up 20-31 months, with an average of 24.1 months. During the follow-up, there was no complication such as wound infection and nerve injury. At last follow-up, the range of motion of shoulder flexion, abduction, and external rotation, the rank of internal rotation vertebra, the VAS score, Constant score, and subacromial space were significantly improved when compared with preoperative ones ( <0.05).

Conclusion: Manipulation under anesthesia combined with arthroscopic capsular release and subacromial debridement can achieve a good mid-term effectiveness without complication for primary frozen shoulder.
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http://dx.doi.org/10.7507/1002-1892.201911033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171525PMC
June 2020

A microfluidics-derived growth factor gradient in a scaffold regulates stem cell activities for tendon-to-bone interface healing.

Biomater Sci 2020 Jul 27;8(13):3649-3663. Epub 2020 May 27.

Center of Sports Medicine of Orthopaedic Department, Southwest hospital, Third Military Medical University, Chongqing 400038, China.

Treatment of tendon-to-bone interface injury has long been challenging in sports medicine. The major obstacle lies with the complicated three-layer structure of the tissue that consists of a bone region with osteocytes, a tendon region with tenocytes and a transitional region with chondrocytes. Conventional tissue engineering approaches using simply biomaterial scaffolds, stem cells and combinations of them had limited abilities to reconstruct the gradient structure with normal biomechanical properties. We herein aim to construct a three-layer structure with bone marrow-derived stem cells and tendon stem cells cultured in a decellularized tendon scaffold, through application of a gradient of biological cues in the longitudinal direction of the scaffold that guides the stem cells to differentiate and remodel the extracellular matrix in response to different medium concentrations in different regions. A microfluidic chip, on which a tree-like flow pattern was implemented, was adopted to create the concentration gradient in a dichotomous manner. We screened for an optimized seeding ratio between the two stem cell types before incubation of the scaffold in the medium concentration gradient and surgical implantation. Histology and immunohistochemistry assessments, both qualitatively and semi-quantitatively, showed that the microfluidic system provided desired guidance to the seeded stem cells that the healing at 8-week post-implantation presented a similar structure to that of a normal tendon-to-bone interface, which was outstanding compared to treatments without gradient guidance, stem cells or scaffolds where chaotic and fibrotic structures were obtained. This strategy offers a potentially translational tissue engineering approach for better outcomes in tendon-to-bone healing.
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http://dx.doi.org/10.1039/d0bm00229aDOI Listing
July 2020

[Circular RNA expression pattern and competing endogenous RNA network involved in rotator cuff tendinopathy].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 May;34(5):608-614

Department of Orthopeadics/Sports Medicine Center, the First Affiliated Hospital of the Army Medical University, Chongqing, 400038, P.R.China.

Objective: To detect the differentially expressed circular RNA (circRNA) in rotator cuff tendinopathy and analyze the potential molecular mechanism of these parental genes.

Methods: Ten supraspinatus tendons donated from patients who underwent tendon repair surgery between June 2018 and June 2019 were used for RNA-sequence. All rotator cuff tendinopathy and normal tendon samples were confirmed by MRI, histological staining, and observation by arthroscopy. All pathological tendons were matched with tendon samples for patients' age, gender, body mass index, and Bonar score. The bioinformatic analysis was performed based on the differentially expressed circRNA and their parental genes, including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and competing endogenous RNA (ceRNA) network construction.

Results: There were 94 differentially expressed circRNAs, including 31 up-regulated and 63 down-regulated, detected between the rotator cuff tendinopathy and normal tendon samples with |log2 fold change (FC)| >2, <0.05. GO analysis showed that the genes were mostly enriched in response to cyclic adenosine monophosphate (cAMP). KEGG pathway analysis showed that the most genes were enriched in extracellular matrix-receptor interaction, protein digestion and absorption, cell cycle, and nuclear factor κB signaling pathway. ceRNA networks showed the interactions among circRNAs, mRNAs, and miRNAs. And circRNA.8951-has-miR-6089-DNMT3B was the most sum max energy.

Conclusion: This bioinformatic study reveals several potential therapeutic targets for rotator cuff tendinopathy, which paves the way to better treatment and prevention of this disorder.
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http://dx.doi.org/10.7507/1002-1892.201911094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171857PMC
May 2020

Comparison of dorsal closing wedge calcaneal osteotomy versus posterosuperior prominence resection for the treatment of Haglund syndrome.

J Orthop Surg Res 2020 May 7;15(1):168. Epub 2020 May 7.

Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street 30, Shapingba District, Chongqing, 400038, China.

Background: Haglund syndrome is a common disease that causes posterior heel pain. This study compared the clinical outcomes of dorsal closing wedge calcaneal osteotomy (DCWCO) and posterosuperior prominence resection (PPR) for the treatment of Haglund syndrome.

Methods: This retrospective study included 12 patients who underwent DCWCO and 32 patients who underwent PPR from January 2010 to August 2016. Patients were evaluated using the American Orthopedic Foot Ankle Society ankle-hindfoot scale (AOFAS), Victorian Institute of Sport Assessment Scale for Achilles tendinopathy (VISA-A), Fowler-Philip angle, Bohler's angle, and calcaneal pitch angle preoperatively and postoperatively (at 3 months, 6 months, 1 year, and the latest follow-up).

Results: Both groups exhibited a significant increase in their AOFAS and VISA-A scores after surgery. The DCWCO group had lower AOFAS scores than the PPR group at 6 months (77.6 ± 5.1 vs. 82.8 ± 7.8; P = 0.037) but had higher scores at the latest follow-up (98.2 ± 2.3 vs. 93.4 ± 6.1; P = 0.030). The DCWCO group had lower VISA-A scores at 3 months (56.9 ± 13.9 vs. 65.2 ± 11.0; P = 0.044) but higher scores at the latest follow-up (98.2 ± 2.6 vs. 94.3 ± 5.0; P = 0.010) than the PPR group. Both groups exhibited significant changes in the Fowler-Philip angle and Bohler's angle after surgery. The postoperative Fowler-Philip angle of the DCWCO group was greater than that of the PPR group (35.9° ± 4.9° vs. 31.4° ± 6.2°; P = 0.026). However, there was no statistically significant difference in any other angle of the two groups postoperatively.

Conclusions: Compared to the PPR group, the DCWCO group had poorer short-term clinical outcomes but provide better long-term function and symptom remission. This method can be a good option for those patients with higher functional expectations.
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http://dx.doi.org/10.1186/s13018-020-01687-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206805PMC
May 2020

Exosomes Derived from Bone Marrow Stromal Cells (BMSCs) Enhance Tendon-Bone Healing by Regulating Macrophage Polarization.

Med Sci Monit 2020 May 5;26:e923328. Epub 2020 May 5.

Sports Medicine Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China (mainland).

BACKGROUND Inflammation after tendon-bone junction injury results in the formation of excessive scar tissue and poor biomechanical properties. Recent research has shown that exosomes derived from bone marrow stromal cells (BMSCs) can modulate inflammation during tissue healing. Thus, our study aimed to enhance tendon-bone healing by use of BMSC-derived exosomes (BMSC-Exos). MATERIAL AND METHODS The mouse tendon-bone reconstruction model was established, and the mice were randomly divided into 3 groups: the control group, the hydrogel group, and the hydrogel+exosome group, with 30 mice in each group. At 7 days, 14 days, and 1 month after surgery, tendon-bone junction samples were harvested, and the macrophage polarization and tendon-bone healing were evaluated based on histology, immunofluorescence, and quantitative RT-PCR (qRT-PCR) analysis. RESULTS In the early phase, we observed significantly higher numbers of M2 macrophages and more anti-inflammatory and chondrogenic-related factors in the hydrogel+BMSC-Exos group compared with the control group and the hydrogel group. The M1 macrophages and related proinflammatory factors decreased. Cell apoptosis decreased in the hydrogel+BMSC-Exos group, while cell proliferation increased; in particular, the CD146+ stem cells substantially increased. At 1 month after surgery, there was more fibrocartilage in the hydrogel+BMSC-Exos group than in the other groups. Biomechanical testing showed that the maximum force, strength, and elastic modulus were significantly improved in the hydrogel+BMSC-Exos group. CONCLUSIONS Our study provides evidence that the local administration of BMSC-Exos promotes the formation of fibrocartilage by increasing M2 macrophage polarization in tendon-to-bone healing, leading to improved biomechanical properties. These findings provide a basis for the potential clinical use of BMSC-Exos in tendon-bone repair.
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http://dx.doi.org/10.12659/MSM.923328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218969PMC
May 2020

Conjoint analysis of lncRNA and mRNA expression in rotator cuff tendinopathy.

Ann Transl Med 2020 Mar;8(6):335

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.

Background: Rotator cuff tendinopathy (RCT) is a common musculoskeletal disorder in the shoulder, whose underlying mechanism is unknown. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles in RCT.

Methods: In this study, we profiled lncRNAs and mRNAs involved in RCT in comparison with the normal tendon (NT) by RNA sequencing (RNA-Seq), to identify potential therapeutic targets. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway, competing endogenous RNA (ceRNA), and co-expression network construction were used to identify the potential functions of these RNAs. Three lncRNAs and three mRNAs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Results: In total, 419 lncRNAs and 1,541 mRNAs were differentially expressed between the RCT and NT groups with a fold change of >2 and P of <0.01. The GO and KEGG pathway analyses showed that the differentially expressed mRNAs were mainly enriched in complement activation and involved in the citrate cycle. The ceRNA network showed the interaction of differentially expressed RNAs, comprising 139 lncRNAs, 126 mRNAs, and 35 miRNAs. , , , , , and were validated by PCR. We constructed a co-expressed network of these validated RNAs.

Conclusions: We preliminarily analyzed the profile of lncRNAs and mRNAs in RCT. The bioinformatic analysis revealed several potential therapeutic targets for RCT.
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http://dx.doi.org/10.21037/atm.2020.02.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186612PMC
March 2020

Molecular functions of FSTL1 in the osteoarthritis.

Int Immunopharmacol 2020 Jun 4;83:106465. Epub 2020 Apr 4.

Department of Orthopedics/Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400038, China; College of Basic Medicine, Army Medical University, Chongqing 400038, China. Electronic address:

Follistatin-like protein 1 (FSTL1) showed overexpression in the inflammatory synovial pannus, serum, and synovial tissues of osteoarthritis (OA) patients. However, FSTL1 knock out (KO) embryos exhibited reduced vertebral cartilage cellularity, extensive skeleton defects and reduced MSCs proliferation. Thus, the role of FSTL1 in chondrocyte proliferation is not completely understood. In vitro studies revealed that Human recombinant FSTL1 (hFSTL1) promoted chondrogenic signals in the MSCs and cell viability only at low concentrations. Recent reports suggest that high levels of FSTL-1 are proposed to enhance inflammatory signals which suppress chondrogenesis leading to cartilage destruction. Altogether, FSTL1 has the potential to promote MSC proliferation and chondrogenic differentiation in a low concentration-dependent manner. However, the mechanism by which FSTL-1 affects MSCs chondrogenic differentiation and chondrogenesis remains unknown. Therefore, this review introduces a deep discussion of FSTL1's molecular functions in the OA pathophysiology, which will contribute to the deep understanding of FSTL1 molecular activity in the OA pathogenesis.
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http://dx.doi.org/10.1016/j.intimp.2020.106465DOI Listing
June 2020

Downregulation of type I collagen expression in the Achilles tendon by dexamethasone: a controlled laboratory study.

J Orthop Surg Res 2020 Feb 24;15(1):70. Epub 2020 Feb 24.

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street. 30, Shapingba District, Chongqing, 400038, China.

Background: Spontaneous Achilles tendon rupture associated with long-term dexamethasone (Dex) use has been reported. However, few studies have investigated the potential mechanism. The aim of this study was to evaluate the effects of oral Dex on type I collagen in humans and rats and its association with tendon rupture.

Methods: First, six Achilles tendons from patients who received long-term Dex treatment, and another six normal tendons were harvested for histological evaluation. Secondly, 8-week-old rats (n = 72) were randomly assigned to a Dex group or a control group. Type I collagen was studied at the mechanical, histological, and molecular levels after 3 and 5 weeks. Tenocytes isolated from normal human and rat tendon were used to investigate the effect of Dex on cellular scale.

Results: Histological analysis of human and rat tendon tissue revealed an irregular, disordered arrangement of type I collagen in the Dex group compared with the control group. In addition, In the Dex+ group, type I collagen expression decreased in comparison with the Dex- group in both human and rat tenocytes. The mechanical strength of tendons was significantly reduced in the Dex group (68.87 ± 11.07 N) in comparison with the control group (81.46 ± 7.62 N, P = 0.013) after 5 weeks. Tendons in the Dex group were shorter with smaller cross-sectional areas (10.71 ± 0.34 mm, 1.44 ± 0.22 mm, respectively) after 5 weeks than those in the control group (11.13 ± 0.50 mm, P = 0.050, 2.74 ± 0.34 mm, P < 0.001, respectively).

Conclusions: This finding suggests long-term use of Dex that decreases the expression of type I collagen at molecular and tissue levels both in human and rat Achilles tendons. Furthermore, Dex decreases the mechanical strength of the tendon, thereby increasing the risk of Achilles tendon rupture.
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http://dx.doi.org/10.1186/s13018-020-01602-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038574PMC
February 2020

Co-cultured Bone-marrow Derived and Tendon Stem Cells: Novel Seed Cells for Bone Regeneration.

Open Life Sci 2019 Jan 31;14:568-575. Epub 2019 Dec 31.

Department of Orthopaedics, First Affiliated Hospital, Army Military Medical University, Chongqing 400038, P.R. China.

Tendon-bone healing after injury is an unsolved problem. Several types of stem cells are used as seed cells. However, the optimal co-culture ratio of different types of cells suitable for tissue engineering as well as the stimulator for facilitating the differentiation of stem cells in tendon-bone healing is unclear. In this study, the proliferation of both bone marrow-derived stem cells (BMSCs) and tendon stem cells (TSCs) was increased at a 1:1 co-cultured ratio, and proliferation was suppressed by Tenascin C (TNC). TNC treatment can promote osteogenesis or chondrogenesis of both BMSCs and TSCs under a 1:1 co-cultured ratio. In addition, the expression level of Rho-associated kinase (ROCK) increased in the process of TNC-induced osteogenesis and decreased in the process of TNC-induced chondrogenesis. Furthermore, the level of insulin-like growth factor 1 receptor (IGF-1R) and mitogen-activated protein kinase (MEK) was upregulated during the osteogenesis and chondrogenesis of both BMSCs and TSCs after TNC treatment. Although our study was conducted in rats with no direct evaluation of the resulting cells for tendon-bone healing and regeneration, we show that the proliferation of BMSCs and TSCs was enhanced under a 1:1 co-cultured ratio. TNC has a significant impact on the proliferation and differentiation of co-cultured BMSCs and TSCs. IGF-IR, ROCK, and MEK may become involved in the process after TNC treatment.
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http://dx.doi.org/10.1515/biol-2019-0063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874801PMC
January 2019

Chinese Consensus on Insertional Achilles Tendinopathy.

Orthop J Sports Med 2019 Oct 11;7(10):2325967119879052. Epub 2019 Oct 11.

H.X. and H.L. contributed equally to this work.

Background: Insertional Achilles tendinopathy (IAT) is a common finding in the clinic. However, consensus on its mechanism, pathological process, diagnosis, treatment, and rehabilitation is lacking. Thus, the Chinese Society of Sports Medicine organized and invited experts representing the fields of ankle disease and tendinopathy to jointly develop an expert consensus on IAT.

Study Design: A consensus statement of the Chinese Society of Sports Medicine.

Methods: A total of 34 experts in the field of sports medicine and orthopaedics were invited to participate in the compilation of a consensus statement regarding IAT. Consensus was achieved according to the Delphi method. First, 10 working groups composed of 34 experts were established to compile draft statements about clinical problems related to IAT by reviewing and analyzing the available literature. An expert consensus meeting to discuss drafts was then arranged. Each statement was individually presented and discussed, followed by a secret vote. Consensus was reached when more than 50% of the experts voted in its favor. The strength of the proposed recommendation was classified based on the proportion of favorable votes: consensus, 51% to 74%; strong consensus, 75% to 99%; unanimity, 100%.

Results: Of the 10 expert consensus statements on the clinical diagnosis and treatment of IAT, there was strong consensus for 8 statements and unanimity for 2 statements.

Conclusion: This expert consensus focused on the concepts, causes, pathological process, clinical diagnosis, and treatment of IAT. Accepted recommendations in these areas which will assist clinicians in carrying out standardized management of related diseases.
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http://dx.doi.org/10.1177/2325967119879052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791038PMC
October 2019

[Effectiveness of Tang's arthroscopy approach for anterior and posterior ankle impingement syndrome].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2019 Nov;33(11):1340-1344

Department of Orthopedics/Sports Medicine Center, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Chongqing, 400038,

Objective: To investigate the effectiveness of Tang's arthroscopy approach in treatment of anterior and posterior ankle impingement syndrome.

Methods: Between August 2010 and September 2017, 92 patients with anterior and posterior ankle impingement syndrome were retrospectively analyzed. There were 58 patients were treated with Tang's arthroscopy approach under floating decubitus (group A) and 34 patients were treated with standard anterior and posterior approaches (group B). There was no significant difference in gender, age, body mass index, side, disease duration, preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score, and preoperative visual analogue scale (VAS) score between the two groups ( >0.05).The operation time, AOFAS score, VAS score, and Roles-Maudsley score were recorded to evaluated the pain and function of the ankle, and patient subjective satisfaction. The X-ray film and MRI at 12 months were used to observe the ankle impingement.

Results: Median operation time of group A was 50.5 minutes [95%CI (49.3, 54.6)], which was significantly shorter than that of group B [88.5 minutes, 95%CI (76.5, 92.8)] (Z=-4.685, =0.000). All incisions in group A healed by first intention; while the incisions of 2 cases in group B delayed healed after debridement. The follow-up time of group A was (54.7±18.8) months, while that of group B was (55.4±17.9) months, and there was no significant difference between the two groups ( =-0.178, =0.859). The lateral X-ray films at 12 months showed that the talus process was removed incompletely in 2 cases (3.4%) of group A and 1 case (2.9%) of group B. There was no significant difference in the incidence between the two groups (χ =0.014, =0.699). At last follow-up, the AOFAS scores were 83.1±6.6 in group A and 85.2±6.4 in group B; the VAS scores were 1.3±1.1 in group A and 1.6±1.0 in group B. The AOFAS and VAS scores at last follow-up were superior to preoperative ones ( <0.05), but there was no significant difference between the two groups ( >0.05). The median subjective satisfaction score of group A was 2.0 [95%(1.4, 1.7)], which was better than that of group B [2.0, 95%(1.6, 2.2)] ( =-2.480, =0.013).

Conclusion: Arthroscopic treatment of anterior and posterior ankle impingement syndrome through Tang's approach can shorten the operation time, simplify the procedures, and obtain good effectiveness and patient satisfaction.
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http://dx.doi.org/10.7507/1002-1892.201904129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337454PMC
November 2019

Aspirin promotes tenogenic differentiation of tendon stem cells and facilitates tendinopathy healing through regulating the GDF7/Smad1/5 signaling pathway.

J Cell Physiol 2020 05 21;235(5):4778-4789. Epub 2019 Oct 21.

Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.

Tendinopathy is a common musculoskeletal system disorder in sports medicine, but regeneration ability of injury tendon is limited. Tendon stem cells (TSCs) have shown the definitive treatment evidence for tendinopathy and tendon injuries due to their tenogenesis capacity. Aspirin, as the representative of nonsteroidal anti-inflammatory drugs for its anti-inflammatory and analgestic actions, has been commonly used in treating tendinopathy in clinical, but the effect of aspirin on tenogenesis of TSCs is unclear. We hypothesized that aspirin could promote injury tendon healing through inducing TSCs tenogenesis. The aim of the present study is to make clear the effect of aspirin on TSC tenogenesis and tendon healing in tendinopathy, and thus provide new treatment evidence and strategy of aspirin for clinical practice. First, TSCs were treated with aspirin under tenogenic medium for 3, 7, and 14 days. Sirius Red staining was performed to observe the TSC differentiation. Furthermore, RNA sequencing was utilized to screen out different genes between the induction group and aspirin treatment group. Then, we identified the filtrated molecules and compared their effect on tenogenesis and related signaling pathway. At last, we constructed the tendinopathy model and compared biomechanical changes after aspirin intake. From the results, we found that aspirin promoted tenogenesis of TSCs. RNA sequencing showed that growth differentiation factor 6 (GDF6), GDF7, and GDF11 were upregulated in induction medium with the aspirin group compared with the induction medium group. GDF7 increased tenogenesis and activated Smad1/5 signaling. In addition, aspirin increased the expression of TNC, TNMD, and Scx and biomechanical properties of the injured tendon. In conclusion, aspirin promoted TSC tenogenesis and tendinopathy healing through GDF7/Smad1/5 signaling, and this provided new treatment evidence of aspirin for tendinopathy and tendon injuries.
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http://dx.doi.org/10.1002/jcp.29355DOI Listing
May 2020

Clinical Guidelines for the Surgical Management of Chronic Lateral Ankle Instability: A Consensus Reached by Systematic Review of the Available Data.

Orthop J Sports Med 2019 Sep 23;7(9):2325967119873852. Epub 2019 Sep 23.

Department of Sports Medicine, Huashan Hospital Fudan University, Shanghai, China.

Background: The surgical management of chronic lateral ankle instability (CLAI) has evolved since the 1930s, but for the past 50 years, the modified Broström technique of ligament repair has been the gold standard. However, with the development of arthroscopic techniques, significant variation remains regarding when and how CLAI is treated operatively, which graft is the optimal choice, and which other controversial factors should be considered.

Purpose: To develop clinical guidelines on the surgical treatment of CLAI and provide standardized guidelines for indications, surgical techniques, rehabilitation strategies, and assessment measures for patients with CLAI.

Study Design: A consensus statement of the Chinese Society of Sports Medicine.

Methods: A total of 14 physicians were queried for their input on guidelines for the surgical management of CLAI. After 9 clinical topics were proposed, a comprehensive systematic search of the literature published since 1980 was performed for each topic through use of China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, EMBASE, and the Cochrane Library. The recommendations and statements were drafted, discussed, and finalized by all authors. The recommendations were graded as grade 1 (strong) or 2 (weak) based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) concept. Based on the input from 28 external specialists independent from the authors, the clinical guidelines were modified and finalized.

Results: A total of 9 topics were covered with regard to the following clinical areas: surgical indications, surgical techniques, whether to address intra-articular lesions, rehabilitation strategies, and assessments. Among the 9 topics, 6 recommendations were rated as strong and 3 recommendations were rated as weak. Each topic included a statement about how the recommendation was graded.

Conclusion: This guideline provides recommendations for the surgical management of CLAI based on the evidence. We believe that this guideline will provide a useful tool for physicians in the decision-making process for the surgical treatment of patients with CLAI.
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http://dx.doi.org/10.1177/2325967119873852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757505PMC
September 2019

Aspirin inhibits adipogenesis of tendon stem cells and lipids accumulation in rat injury tendon through regulating PTEN/PI3K/AKT signalling.

J Cell Mol Med 2019 11 26;23(11):7535-7544. Epub 2019 Sep 26.

Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.

Tendon injury repairs are big challenges in sports medicine, and fatty infiltration after tendon injury is very common and hampers tendon injury healing process. Tendon stem cells (TSCs), as precursors of tendon cells, have shown promising effect on injury tendon repair for their tenogenesis and tendon extracellular matrix formation. Adipocytes and lipids accumulation is a landmark event in pathological process of tendon injury, and this may induce tendon rupture in clinical practice. Based on this, it is important to inhibit TSCs adipogenesis and lipids infiltration to restore structure and function of injury tendon. Aspirin, as the representative of non-steroidal anti-inflammatory drugs (NSAIDs), has been widely used in tendon injury for its anti-inflammatory and analgesic actions, but effect of aspirin on TSCs adipogenesis and fatty infiltration is still unclear. Under adipogenesis conditions, TSCs were treated with concentration gradient of aspirin. Oil red O staining was performed to observe changes of lipids accumulation. Next, we used RNA sequencing to compare profile changes of gene expression between induction group and aspirin-treated group. Then, we verified the effect of filtrated signalling on TSCs adipogenesis. At last, we established rat tendon injury model and compared changes of biomechanical properties after aspirin treatment. The results showed that aspirin decreased lipids accumulation in injury tendon and inhibited TSCs adipogenesis. RNA sequencing filtrated PTEN/PI3K/AKT signalling as our target. After adding the signalling activators of VO-Ohpic and IGF-1, inhibited adipogenesis of TSCs was reversed. Still, aspirin promoted maximum loading, ultimate stress and breaking elongation of injury tendon. In conclusion, by down-regulating PTEN/PI3K/AKT signalling, aspirin inhibited adipogenesis of TSCs and fatty infiltration in injury tendon, promoted biomechanical properties and decreased rupture risk of injury tendon. All these provided new therapeutic potential and medicine evidence of aspirin in treating tendon injury and tendinopathy.
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http://dx.doi.org/10.1111/jcmm.14622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815914PMC
November 2019

[Mid-term effectiveness of arthrolysis and hinged external fixation for treatment of stiff elbow caused by heterotrophic ossification].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2019 Oct;33(10):1299-1304

Department of Orthopedics/Sports Medicine Center, the First Affiliated Hospital of Army Medical University of Chinese PLA, Chongqing, 445000,

Objective: To evaluate the mid-term effectiveness of arthrolysis and hinged external fixation for the treatment of stiff elbow caused by heterotrophic ossification.

Methods: Between January 2014 and December 2017, 11 patients with stiff elbow caused by heterotrophic ossification were admitted. There were 9 males and 2 females with an average age of 32 years (range, 14-48 years), and left side in 6 cases and right side in 5 cases. The cause of stiff elbow included humerus fracture in 5 cases, ulna fracture in 2 cases, fracture of capitulum radii in 1 case, dislocation of capitulum radii in 1 case, terrible triad of the elbow in 1 case, and soft tissue injury in 1 case. The disease duration ranged from 7 to 18 months (mean, 11 months). Preoperative active range of motion of elbow was (19.6±17.5)° and Mayo score was 34.1±9.7. All patients received the treatment of arthrolysis and debridement of heterotrophic ossification lesion combining hinged external fixator, and active and passive rehabilitation with the help of hinged external fixator. The hinged external fixators were removed after 2 months.

Results: All patients were followed up 13-36 months (mean, 19.1 months). All incisions healed by first intention, and no complication of infection or nerve lesion occurred postoperatively. At last follow-up, the results of X-ray films showed that no heterotrophic ossification recurred. The active range of motion of elbow was (116.4±16.6)° and Mayo score was 93.2±7.8, showing significant differences when compared with preoperative ones ( =17.508, =0.000; =16.618, =0.000).

Conclusion: The application of arthrolysis and debridement of heterotrophic ossification lesion combining hinged external fixator can improve the elbow's range of motion significantly and obtain a good mid-term effectiveness.
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http://dx.doi.org/10.7507/1002-1892.201902002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337636PMC
October 2019

[Research progress of structured repair of tendon-bone interface].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2019 Sep;33(9):1064-1070

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn, and Combined Injury, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Chongqing, 400038,

In sports system, the tendon-bone interface has the effect of tensile and bearing load, so the effect of healing plays a crucial role in restoring joint function. The process of repair is the formation of scar tissue, so it is difficult to achieve the ideal effect for morphology and biomechanical strength. The tissue engineering method can promote the tendon-bone interface healing from the seed cells, growth factors, and scaffolds, and is a new direction in the field of development of the tendon-bone interface healing.
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http://dx.doi.org/10.7507/1002-1892.201811139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355852PMC
September 2019
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