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.

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism.

Osteonecrosis of the femoral head (ONFH) is a common disabling disease. Copper has positive effects on cells that regulate bone metabolism. However, the relationship between copper metabolism (CM) and steroid-induced ONFH (SONFH) remains unclear. The GSE123568 dataset was downloaded from the Gene Expression Omnibus. The differentially expressed CM-related SONFH genes (DE-CMR-SONFHGs) were identified via differential analysis and weighted gene coexpression network analysis (WGCNA). Receiver operating characteristic (ROC) analysis was performed for the predictive accuracy of key genes. Targeting drugs and the copper death-related genes (CDRGs) relevant to key genes were investigated. The bioinformatics results were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Two out of 106 DE-CMR-SONFHGs were identified as key genes (PNP and SLC2A1), which had diagnostic value in distinguishing SONFH from control samples and were related to various immune cell infiltrations. Eleven PMP-targeting drugs and five SLC2A1-targeting drugs were identified. The qRT-PCR, as well as WB, results confirmed the downregulation PNP and SLC2A1 and high expression of the CDRGs DLD, PDHB, and MTF1, which are closely related to these two key genes. In conclusion, PNP and SLC2A1 were identified as key genes related to SONFH and may provide insights for SONFH treatment.

Metacarpal Lengthening Using a Mini-Ring Ilizarov Device for Thumb Reconstruction.

PURPOSE: To explore the results of using the mini-ring Ilizarov external fixator for thumb metacarpal lengthening and its compatibility with a simultaneous groin flap. METHODS: From May 2016 to June 2019, 17 adult patients with thumb loss were treated with metacarpal lengthening using a mini-ring Ilizarov device. The device was composed of 2 rings, threaded rods, nuts, and K-wires (diameter, 1.5 mm). Of these patients, 6 also underwent simultaneous groin flap transfer. Lengthening was started 3 days after surgery at a rate of 0.66 mm/d. The pedicle of the groin flap was divided 1 month after the surgery. The healing index (days per cm), which denotes the number of days the external fixator is attached to the bone per centimeter of length gained, was used to evaluate the lengthening efficiency. RESULTS: The patients were observed for 21.9 ± 9.0 months. The lengthening continued for 29.1 ± 4.5 days, resulting in an additional length of 1.9 ± 0.3 cm. CONCLUSIONS: The mini-ring Ilizarov external fixator is a simple device for primary metacarpal lengthening. This device can be used with a groin flap for single-stage lengthening of injured thumbs with bone exposure. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

[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.

ERECTA regulates seed size independently of its intracellular domain via MAPK-DA1-UBP15 signaling.

Seed size is determined by the coordinated growth of the embryo, endosperm, and integument. Growth of the integument is initiated by signal molecules released from the developing endosperm or embryo. Although recent studies have identified many components that regulate seed size by controlling integument growth, the upstream signals and the signal transduction pathway that activate these components after double fertilization are unclear. Here, we report that the receptor-like kinase ERECTA (ER) controls seed size by regulating outer integument cell proliferation in Arabidopsis thaliana. Seeds from er mutants were smaller, while those from ER-overexpressing plants were larger, than those of control plants. Different from its role in regulating the development of other organs, ER regulates seed size via a novel mechanism that is independent of its intracellular domain. Our genetic and biochemical data show that a MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) signaling pathway comprising MAPK-KINASE 4/5, MAPK 3/6 (MPK3/6), DA1, and UBIQUITIN SPECIFIC PROTEASE 15 (UBP15) functions downstream of ER and modulates seed size. MPK3/6 phosphorylation inactivates and destabilizes DA1 to increase the abundance of UBP15, promoting outer integument cell proliferation and increasing seed size. Our study illustrates a nearly completed ER-mediated signaling pathway that regulates seed size and will help uncover the mechanism that coordinates embryo, endosperm, and integument growth after double fertilization.

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.

Feasibility of cortical bone trajectory screws for bridging fixation in revision surgery for lumbar adjacent segment degeneration.

BACKGROUND: To investigate the feasibility of using cortical bone trajectory (CBT) screws for bridging fixation in revision surgery for lumbar adjacent segment degeneration and to provide a reference for clinical practice. METHODS: Computed tomography scans of the lumbar spines of 36 patients in our hospital were used. Sixteen males and 20 females with an average age of 65.5 ±â€Š10.5 years (range: 46 to 83 years) were included. Three-dimensional reconstruction was performed using computer software. Screws with appropriate sizes were selected for the L1 to L5 vertebral segments, and traditional pedicle screws were placed using the standard method. After completing screw placement, simulated placement of CBT screws was performed separately. No overlap occurred between the two screws in the process of CBT screw placement, and the placement point and direction were adjusted until screw placement completion. After all screw placement simulations were complete, according to the contact area of the cortical bone of the screw trajectory and the screw puncture position and distance through the trajectory, the screw placement results were categorized as excellent, good, general, and failure. Excellent and good ratings were considered successful, while a general rating was regarded as acceptable. Then, the success rate and acceptable rate of each segment of the lumbar spine were calculated. RESULTS: Three hundred and sixty screw placement simulations were performed in lumbar pedicles, and 72 CBT screws were implanted in each vertebral body of the lumbar spine. The success rates in the L1 to L5 segments were 73.6%, 80.6%, 83.3%, 88.9%, and 77.8%, respectively, and the acceptable rates were 91.7%, 97.2%, 97.2%, 100%, and 91.7%, respectively. The overall success rate and acceptable rate of CBT screw placement in the lumbar spine were 80.8% and 95.6%, respectively. CONCLUSION: CBT screws are feasible for bridging fixation in lumbar adjacent segment degeneration revision surgery, and the accuracy of screw placement in different lumbar vertebrae varies.

Muscle pedicle bone flap transplantation for treating femoral neck fracture in adults: a systematic review.

BACKGROUND: This systematic review was conducted to gather available evidence on the effectiveness of muscle pedicle bone flap transplantation in adult patients with femoral neck fractures. METHODS: Databases such as PubMed, EMBASE, IEEE, Web of Science, and Cochrane library were searched from their dates of inception until March 2021. Two reviewers independently selected the interventional studies on the assessment of the effectiveness of muscle pedicle bone flap transplantation for femoral neck fractures; data extraction and assessment of the methodological quality as per the Institute of Health Economics quality appraisal checklist were also performed by the reviewers. The effectiveness and complication outcomes were assessed by calculating the average rates. RESULTS: Overall, 20 studies with 1022 patients were included in this review. Notably, the methodologic quality of the included studies was typically poor. The average effective rates were as follows: good, 73.4%; fair, 15.4%; and poor, 10.9%. Moreover, the average nonunion rate, average avascular necrosis rate, average collapse rate, and the overall reoperation rate were 9.0%, 6.7%, 4.7%, and 7.3%, respectively. CONCLUSIONS: This systematic review of heterogeneous studies with varying number of patients and varying surgical techniques indicated that muscle pedicle bone flap transplantation provides promising results with low rates of avascular necrosis and nonunion. Nevertheless, further controlled studies are required to ascertain the effectiveness of muscle pedicle bone flap transplantation in treating femoral neck fracture.

Comparison of the 3D-printed operation guide template technique and the free-hand technique for S2-alar-iliac screw placement.

BACKGROUND: To compare the safety and accuracy of the 3D-printed operation guide template technique and the free-hand technique in the placement of the S2-alar-iliac (S2AI) screw. METHODS: We conducted a retrospective analysis of 47 patients undergoing S2AI screw placement in our hospital, divided into the 3D-printed operation guide template group and the free-hand screw placement group. The duration of single S2AI screw placement was documented in all patients. A postoperative CT scan was performed to assess screw placement effectiveness according to the distance from the screw tip to the breach of the cortical bone wall. RESULTS: In total, 42 screws were placed in the guide template group, with an average screw placement duration of 151.6 ± 44.8 s. Screw placement grading was as follows: 40 screws in grade 0, two in grade 1, and none in grades 2 and 3. This grading resulted in excellent and good rates of 95.2% and 100%, respectively. In total, 52 screws were placed in the free-hand group, with an average screw placement duration of 138.3 ± 45.9 s. Screw placement grading was as follows: 42 screws in grade 0, seven in grade 1, three in grade 2, and none in grade 3. This grading resulted in excellent, good and acceptable rates 80.8%, 94.2% and 100%, respectively. Screw placement duration did not significantly differ between the groups (p > 0.05). The excellent rate of screw placement was greater in the guide template group than in the free-hand group (p < 0.05), but the good and acceptable rates did not significantly differ between the two groups (p > 0.05). CONCLUSION: Both techniques can be applied to S2AI screw placement. The 3D-printed guide technique is superior to the free-hand technique in terms of safety and accuracy.

Clinical Application of 3-Dimensional Printed Navigation Templates in Treating Femoral Head Osteonecrosis With Pedicled Iliac Bone Graft.

OBJECTIVE: The aim of the study was to explore the feasibility and early effect of digital design combined with 3-dimensional (3D) printing technique in the transplantation of vascular pedicled iliac bone flap in the treatment of avascular necrosis of the femoral head. METHODS: The navigation template was designed according to computed tomography scan and printed in 3D printing technique before operation, which was used to guide the localization and clearance of osteonecrosis of the femoral head in vascular pedicled iliac bone flap transplantation. In blank control group, 28 cases (32 hips) of osteonecrosis of the femoral head were treated with vascular pedicled iliac bone flap without the assistance of 3D navigation template from February 2002 to February 2009, including 19 males (21 hips) and 9 females (11 hips), with an average age of 37 years (range, 20-61 years). There were 12 cases of left hip, 16 cases of right hip, and 4 cases of double hip. According to the International Association of Bone Circulation staging, there were 8 hips in stage II B, 9 hips in stage II C, 8 hips in stage III B, and 7 hips in stage III C. In the experimental group, from February 2014 to June 2014, 15 patients (24 hips) with avascular necrosis of the femoral head were treated with vascular pedicled iliac bone flap with the aid of 3D navigation template. There were 11 males (17 hips) and 4 females (7 hips) with an average age of 38 years (range, 18-56 years). There were 2 cases of left hip, 4 cases of right hip, and 9 cases of double hip. According to the International Association of Bone Circulation staging, there were 5 hips in stage II B, 8 hips in stage II C, 6 hips in stage III B, and 5 hips in stage III C. The operation time, bleeding volume, and postoperative Harris score of the experimental group and the control group were statistically analyzed. RESULTS: The incisions in both groups healed in the first stage, and there were no operation-related complications such as deep venous thrombosis and infection of lower extremities. All patients were followed up for 12 to 16 months (with an average of 14 months). On the second day after operation, X-ray and computed tomography showed that the necrotic focus of the femoral head and the surrounding sclerotic bone was completely removed, and the position of the vascular pedicled iliac bone flap was satisfactory and did not penetrate the articular surface. The iliac bone flap and bone graft achieved bony fusion. In the navigation template group, the mean ± SD operation time was 135.38 ± 9.49 minutes, the mean ± SD blood loss was 225.13 ± 13.41 mL, the mean ± SD postoperative Harris score was 89.53 ± 5.83, 12 hips were excellent, 10 hips were good, and 2 hips were moderate, whereas in the group without navigation template, the mean ± SD operation time was 151.00 ± 15.28 minutes, the mean ± SD blood loss was 283.56 ± 30.60 mL, the mean ± SD postoperative Harris score was 83.32 ± 3.75, 15 hips were excellent, 14 hips were good, and 3 hips were fair. By independent sample t test, there were significant differences in average operation time, average blood loss, and postoperative Harris score between the 2 groups (P < 0.05). CONCLUSIONS: Compared with not using navigation template, vascular pedicled iliac bone flap combined with navigation template in the treatment of osteonecrosis of femoral head could locate the area of osteonecrosis of femoral head more accurately, shorten the time of operation, and reduce the amount of bleeding during operation. Postoperative hip joint function recovery was better, and the early effect was satisfactory.

[Research progress of artificial wrist joint prosthesis].

Objective: To summarize the research progress of the artificial wrist joint prosthesis. Methods: Domestic and abroad literature concerning artificial wrist joint prosthesis was reviewed and analyzed thoroughly. Results: Artificial wrist joint prosthesis has been developed to the 4th generation. The artificial wrist joint arthroplasty has advantages of pain relief and functional improvement and can achieve ideal short-term effectiveness. But there are some problems, such as loosening, subsidence, fracture, and dislocation of prosthesis. The long-term effectiveness of the 3rd and 4th generation prosthesis still need to be followed up. Conclusion: The biomechanics of wrist joint is extremely complicated, which results in less application and slow development of artificial wrist joint prosthesis. Early-term effectiveness of artificial wrist joint arthroplasty is basically satisfactory, but there are still some long-term complications. So the artificial wrist joint prosthesis remains to be developed.

The Brassinosteroid-Activated BRI1 Receptor Kinase Is Switched off by Dephosphorylation Mediated by Cytoplasm-Localized PP2A B' Subunits.

Brassinosteroid (BR) binding activates the receptor kinase BRI1 by inducing heterodimerization with its co-receptor kinase BAK1; however, the mechanisms that reversibly inactivate BRI1 remain unclear. Here we show that cytoplasm-localized protein phosphatase 2A (PP2A) B' regulatory subunits interact with BRI1 to mediate its dephosphorylation and inactivation. Loss-of-function and overexpression experiments showed that a group of PP2A B' regulatory subunits, represented by B'η, negatively regulate BR signaling by decreasing BRI1 phosphorylation. BR increases the expression levels of these B' subunits, and B'η interacts preferentially with phosphorylated BRI1, suggesting that the dynamics of BR signaling are modulated by the PP2A-mediated feedback inactivation of BRI1. Compared with PP2A B'α and B'ß, which promote BR responses by dephosphorylating the downstream transcription factor BZR1, the BRI1-inactivating B' subunits showed similar binding to BRI1 and BZR1 but distinct subcellular localization. Alteration of the nuclear/cytoplasmic localization of the B' subunits revealed that cytoplasmic PP2A dephosphorylates BRI1 and inhibits the BR response, whereas nuclear PP2A dephosphorylates BZR1 and activates the BR response. Our findings not only identify the PP2A regulatory B subunits that mediate the binding and dephosphorylation of BRI1, but also demonstrate that the subcellular localization of PP2A specifies its substrate selection and distinct effects on BR signaling.