[Progress and prospect of biological treatment for rotator cuff injury repair].

Objective: To review the research progress in biotherapy of rotator cuff injury in recent years, in order to provide help for clinical decision-making of rotator cuff injury treatment. Methods: The literature related to biotherapy of rotator cuff injury at home and abroad in recent years was widely reviewed, and the mechanism and efficacy of biotherapy for rotator cuff injury were summarized from the aspects of platelet-rich plasma (PRP), growth factors, stem cells, and exosomes. Results: In order to relieve patients' pain, improve upper limb function, and improve quality of life, the treatment of rotator cuff injury experienced an important change from conservative treatment to open surgery to arthroscopic rotator cuff repair. Arthroscopic rotator cuff repair plus a variety of biotherapy methods have become the mainstream of clinical treatment. All kinds of biotherapy methods have ideal mid- and long-term effectiveness in the repair of rotator cuff injury. The biotherapy method to promote the healing of rotator cuff injury is controversial and needs to be further studied. Conclusion: All kinds of biotherapy methods show a good effect on the repair of rotator cuff injury. It will be an important research direction to further develop new biotherapy technology and verify its effectiveness.

Pmepa1 knockdown alleviates SpA-induced pyroptosis and osteogenic differentiation inhibition of hBMSCs via p38MAPK/NLRP3 axis.

BACKGROUND: Osteomyelitis is a refractory bone infectious disease, which usually results in progressive bone destruction and bone loss. The invasion of pathogens and subsequent inflammatory response could damage bone marrow mesenchymal stem cells (BMSCs) and inhibit osteogenic differentiation, and finally aggravate uncontrolled bone remodeling in osteomyelitis by affecting bone formation. Exploring the mechanisms of BMSCs injury and osteogenic differentiation inhibition may would help us to find potential therapeutic targets. METHOD: Firstly, staphylococcal protein A (SpA)-treated human bone marrow mesenchymal stem cells (hBMSCs) were used to construct cell models of osteomyelitis. Secondly, transcriptome sequencing was performed to screen differentially expressed genes and then verified the expression of target genes. Next, in vitro experiments were conducted to explore the functions and mechanisms of prostate transmembrane protein androgen induced 1 (Pmepa1) in SpA-treated hBMSCs. Finally, the rat model of osteomyelitis was established to provide an auxiliary validation of the in vitro experimental results. RESULTS: We found that SpA treatment induced inflammatory injury and inhibited osteogenic differentiation in hBMSCs, then the transcriptome sequencing and further detection results showed that Pmepa1 was significantly upregulated in this process. Functionally, Pmepa1 knockdown alleviated inflammatory injury and promoted osteogenic differentiation in SpA-treated hBMSCs. Among them, it was demonstrated that Pmepa1 knockdown exerted cytoprotective effects by alleviating pyroptosis of SpA-infected hBMSCs. Furthermore, recovery experiments revealed that Pmepa1 knockdown reversed SpA-mediated adverse effects by downregulating the p38MAPK/NLRP3 axis. Finally, the detection results of rat femoral osteomyelitis showed that the expression of Pmepa1 was up-regulated, and the expression trends of other indicators including p38MAPK, NLRP3, and caspase-1 were also consistent with the in vitro model. CONCLUSION: Pmepa1 knockdown alleviates SpA-induced pyroptosis and inhibition of osteogenic differentiation in hBMSCs by downregulating p38MAPK/NLRP3 signaling axis. Modulating the expression of Pmepa1 may be a potential strategy to ameliorate osteomyelitis.

Exploring the molecular mechanisms of the involvement of GZMB-Caspase-3-GSDME pathway in the progression of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease with an unclear pathogenesis. Granzyme B (GZMB) has been reported as a potential therapeutic target for RA treatment, but its mechanism remains unclear. This study aimed to explore the molecular mechanism of the GZMB-Caspase-3-GSDME pathway in the progression of RA. An SD rat model of RA was constructed, and Western blot analysis was used to verify the high expression of the GZMB gene in RA rats. Functional validation was then performed on two common RA cells, HFLS-RA cells and MH7A cells, by inhibiting the GZMB gene with the GZMB siRNA virus. Cell proliferation function was measured by CCK8 and EDU assays; cell pyroptosis markers were detected by the LDH assay; inflammation factor levels were measured by ELISA; and the expression of GZMB and pathway-related genes and proteins was measured by Western blot. After GZMB silencing, cell proliferation was decreased compared to the control group, and the inflammation factors IL-1b and IL-18, as well as the pyroptosis markers LDH, IL-1b, and IL-18, were all reduced. The GZMB-related proteins GZMB, caspase-3, and Gasdermin E (GSDME) were also decreased. Therefore, GZMB silencing reduces pyroptosis by inhibiting caspase-3 and Gasdermin E decomposition. In summary, GZMB silencing inhibits the activation of caspase-3 and Gasdermin E, thereby delaying inflammation in RA. The GZMB gene may be a potential therapeutic target for RA.

[Three-dimensional finite element model construction and biomechanical analysis of customized titanium alloy lunate prosthesis].

Objective: To design customized titanium alloy lunate prosthesis, construct three-dimensional finite element model of wrist joint before and after replacement by finite element analysis, and observe the biomechanical changes of wrist joint after replacement, providing biomechanical basis for clinical application of prosthesis. Methods: One fresh frozen human forearm was collected, and the maximum range of motions in flexion, extension, ulnar deviation, and radialis deviation tested by cortex motion capture system were 48.42°, 38.04°, 35.68°, and 26.41°, respectively. The wrist joint data was obtained by CT scan and imported into Mimics21.0 software and Magics21.0 software to construct a wrist joint three-dimensional model and design customized titanium alloy lunate prosthesis. Then Geomagic Studio 2017 software and Solidworks 2017 software were used to construct the three-dimensional finite element models of a normal wrist joint (normal model) and a wrist joint with lunate prosthesis after replacement (replacement model). The stress distribution and deformation of the wrist joint before and after replacement were analyzed for flexion at and 15°, 30°, 48.42°, extension at 15°, 30°, and 38.04°, ulnar deviation at 10°, 20°, and 35.68°, and radial deviation at 5°, 15°, and 26.41° by the ANSYS 17.0 finite element analysis software. And the stress distribution of lunate bone and lunate prosthesis were also observed. Results: The three-dimensional finite element models of wrist joint before and after replacement were successfully constructed. At different range of motion of flexion, extension, ulnar deviation, and radial deviation, there were some differences in the number of nodes and units in the grid models. In the four directions of flexion, extension, ulnar deviation, and radial deviation, the maximum deformation of wrist joint in normal model and replacement model occurred in the radial side, and the values increased gradually with the increase of the range of motion. The maximum stress of the wrist joint increased gradually with the increase of the range of motion, and at maximum range of motion, the stress was concentrated on the proximal radius, showing an overall trend of moving from the radial wrist to the proximal radius. The maximum stress of normal lunate bone increased gradually with the increase of range of motion in different directions, and the stress position also changed. The maximum stress of lunate prosthesis was concentrated on the ulnar side of the prosthesis, which increased gradually with the increase of the range of motion in flexion, and decreased gradually with the increase of the range of motion in extension, ulnar deviation, and radialis deviation. The stress on prosthesis increased significantly when compared with that on normal lunate bone. Conclusion: The customized titanium alloy lunate prosthesis does not change the wrist joint load transfer mode, which provided data support for the clinical application of the prosthesis.

[Research progress in etiology and clinical diagnosis and treatment of scaphotrapeziotrapezoid osteoarthritis].

Objective: To summarize the research progress of scaphotrapeziotrapezoid osteoarthritis (STT OA) and its etiology and clinical treatment. Methods: The domestic and foreign literature on STT OA in recent years was reviewed and the research progress was summarized. Results: STT OA is a common OA, which is highly prevalent in postmenopausal women and diagnosed by wrist X-ray films. The current treatment methods include conservative treatment and surgery. Among them, the conservative treatment can relieve clinical symptoms, but the long-term effectiveness is not ideal. In surgical treatment, scaphoid arthrodesis can effectively relieve wrist pain, but it sacrifices part of the range of motion and grip strength of the wrist, and there is a risk of fusion failure. Distal scaphoid resection and trapezium resection have the advantages of short operation time, simple operation, less damage to the joint capsule and ligament, and shorter postoperative external fixation time, but they lead to changes in carpal bone alignment and dorsal intercalated segmental instability. Arthroplasty can provide pain relief while restoring grip strength and preserving wrist motion, but there is a risk of dislocation of the prosthesis. Conclusion: At present, there is no gold standard for the STT OA treatment. The short-term effectiveness of arthroplasty and arthroscopic distal scaphoid resection are satisfactory, but the long-term effectiveness needs further study.

Diagnostic signature, subtype classification, and immune infiltration of key m6A regulators in osteomyelitis patients.

Background: As a recurrent inflammatory bone disease, the treatment of osteomyelitis is always a tricky problem in orthopaedics. N6-methyladenosine (m6A) regulators play significant roles in immune and inflammatory responses. Nevertheless, the function of m6A modification in osteomyelitis remains unclear. Methods: Based on the key m6A regulators selected by the GSE16129 dataset, a nomogram model was established to predict the incidence of osteomyelitis by using the random forest (RF) method. Through unsupervised clustering, osteomyelitis patients were divided into two m6A subtypes, and the immune infiltration of these subtypes was further evaluated. Validating the accuracy of the diagnostic model for osteomyelitis and the consistency of clustering based on the GSE30119 dataset. Results: 3 writers of Methyltransferase-like 3 (METTL3), RNA-binding motif protein 15B (RBM15B) and Casitas B-lineage proto-oncogene like 1 (CBLL1) and three readers of YT521-B homology domain-containing protein 1 (YTHDC1), YT521-B homology domain-containing family 3 (YTHDF2) and Leucine-rich PPR motif-containing protein (LRPPRC) were identified by difference analysis, and their Mean Decrease Gini (MDG) scores were all greater than 10. Based on these 6 significant m6A regulators, a nomogram model was developed to predict the incidence of osteomyelitis, and the fitting curve indicated a high degree of fit in both the test and validation groups. Two m6A subtypes (cluster A and cluster B) were identified by the unsupervised clustering method, and there were significant differences in m6A scores and the abundance of immune infiltration between the two m6A subtypes. Among them, two m6A regulators (METTL3 and LRPPRC) were closely related to immune infiltration in patients with osteomyelitis. Conclusion: m6A regulators play key roles in the molecular subtypes and immune response of osteomyelitis, which may provide assistance for personalized immunotherapy in patients with osteomyelitis.

Safety and efficacy of a novel three-dimensional printed microporous titanium prosthesis for total wrist arthroplasty in the treatment of end-stage wrist arthritis.

Background: Total wrist arthroplasty is an effective treatment for end-stage wrist arthritis from all causes. However, wrist prostheses are still prone to complications such as prosthesis loosening and periprosthetic fractures after total wrist arthroplasty. This may be due to the wrist prosthesis imprecise matching with patient's bone. In this study, we designed and developed a personalized three-dimensional printed microporous titanium artificial wrist prosthesis (3DMT-Wrist) for the treatment of end-stage wrist joint, and investigated its safety and effectiveness. Methods: Total wrist arthroplasty was performed using 3DMT-Wrist in 14 cases of arthritis between February 2019 and December 2021. Preoperative and postoperative visual analog scale scores, QuickDASH scores, wrist range of motion, and wrist grip strength were evaluated. Data were statistically analyzed using the paired samples t-test. Results: After 19.7 ± 10.7 months of follow-up, visual analog scale decreased from 66.3 ± 8.9 to 6.7 ± 4.4, QuickDASH scores decreased from 47.4 ± 7.3 to 28.2 ± 7.6, grip strength increased from 5.6 ± 1.4 to 17.0 ± 3.3 kg. The range of motion improved significantly in palmar flexion (30.1° ± 4.9° to 44.9° ± 6.5°), dorsal extension (15.7° ± 3.9° to 25.8° ± 3.3°), ulnar deviation (12.2° ± 3.9° to 20.2° ± 4.3°) and radial deviation (8.2° ± 2.3° to 16.2 ± 3.1). No dislocation or loosening of the prosthetic wrist joint was observed. Conclusion: Total wrist arthroplasty using 3DMT-Wrist is a safe and effective new treatment for various types of end-stage wrist arthritis; it offers excellent pain relief and maintains the range of motion.