Causal association of genetically determined plasma metabolites with osteoarthritis: a two-sample Mendelian randomization study.

Background: We aimed to elucidate the causal relationship between plasma metabolites and the vulnerability to Osteoarthritis (OA), encompassing both hip OA and knee OA. Methods: We conducted a two-way two-sample Mendelian randomization (MR) analysis to investigate the association of 1,400 plasma metabolites with OA. The Inverse Variance Weighted (IVW) model served as the primary two-sample MR Analysis method, with supplementary analysis using the Weighted Median (WM) and MR Egger methods. To ensure the robustness of our findings, sensitivity analyses were performed, incorporating Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and Leave-One-Out analyses. To validate the identified metabolites, we utilized the Steiger test and linkage disequilibrium score regression. Results: A total of 94 plasma metabolites were associated with osteoarthritis, with 60 associated with hip OA and 106 associated with knee OA. IVW analysis revealed that tryptophan levels showed the strongest positive association with hip OA (OR [95% CI]: 1.119 [1.024, 1.223]), while X-24757 levels exhibited the highest positive association with knee osteoarthritis (OR [95% CI]: 1.095 [1.032, 1.162]). Ethylparaben sulfate levels were found to have the greatest positive association with hip OA (OR [95% CI]: 1.118 [1.015, 1.231]). Notably, the plasma metabolite X-2475 showed a strong robust random effect across all three types of osteoarthritis. Metabolic pathway analysis revealed that the pathogenesis of osteoarthritis in the hip was mediated by acetylarginine, specifically in four important metabolic pathways: ethanol degradation (p = 0.044), amino sugar metabolism (p = 0.090), fatty acid biosynthesis (p = 0.095), and aspartate metabolism (p = 0.097816). Conclusion: There is a significant association between tryptophan levels and the risk of hip OA, as well as X-24757 levels and the risk of knee osteoarthritis. Additionally, X-24757 levels are also linked to the risk of hip OA. Moreover, this study has identified four crucial metabolic pathways in hip osteoarthritis, which are all regulated by acetylarginine. These findings provide valuable insights into potential biomarkers for OA and highlight potential pathways for its prevention and clinical intervention.

[A new fluoroscopic view to evaluate the medial and lateral articular reduction quality in patella fractures during internal fixation].

Objective: To introduce a new fluoroscopic method for assessing the quality of medial and lateral joint surface reduction during internal fixation of patellar fractures and to summarize the clinical outcomes of patients treated using this method. Methods: A retrospective analysis was conducted on the clinical data of 52 patients with patellar fractures treated between January 2018 and January 2022 who met the inclusion criteria. There were 27 male and 25 female patients, aged 21-75 years, with an average age of 62 years. The types of patellar fractures included 9 transverse fractures, 37 comminuted fractures, and 6 longitudinal fractures. According to the AO/Orthopaedic Trauma Association (AO-OTA)-2018 fracture classification, there were 21 cases of type 34A, 6 cases of type 34B, and 25 cases of type 34C. The time from injury to operation ranged from 1 to 5 days, with an average of 2.3 days. Treatments included internal fixation with hollow screws or hollow screw tension bands, with or without anchor repair. During operation, the medial and lateral joint surfaces of the patella were observed using the tangential fluoroscopic method to assess the smoothness of reduction of the median ridge, lateral joint surface, medial joint surface, and lateral joint edge. Patients were followed up regularly, and X-ray films were taken to observe fracture healing. Knee joint range of motion, Böstman score, and Lysholm score were used to evaluate functional recovery. Results: The tangential fluoroscopic method for the medial and lateral joint surfaces of the patella during operation showed satisfactory reduction of the joint surfaces and good positioning of the implants. All patients were followed up 12-16 months, with an average of 13.4 months. During the follow-up, fracture displacement occurred in 1 case and titanium cable breakage in 1 case. All patella fractures healed successfully, with a healing time of 8-16 weeks (mean, 11.4 weeks). At last follow-up, knee joint range of motion ranged from 120° to 140°, with an average of 136°. The Böstman score ranged from 20 to 30, with an average of 28, yielding excellent results in 45 cases and good results in 7 cases. The Lysholm score ranged from 88 to 100, with an average of 93, yielding excellent results in 40 cases and good results in 12 cases. Conclusion: The intraoperative application of the tangential fluoroscopic method for the medial and lateral joint surfaces of the patella can quickly determine the fluoroscopic plane of the patella, accurately assess the quality of fracture reduction and the position of internal fixator, thereby improving effectiveness.

[Surgical treatment methods and classification of proximal clavicle fracture].

OBJECTIVE: To summarize the surgical treatment of different proximal clavicle fractures, and discuss the classification of proximal clavicle fractures. METHODS: Total of 24 patients with displaced proximal clavicle fractures were treated from January 2017 to December 2020 including 16 males and 8 females, aged 28 to 66 years old. Among them, 20 cases were fresh fractures and 4 cases were old fractures. According to the Edinburgh classification, 14 cases were type 1B1 fractures and 10 cases were type 1B2 fractures. The different internal fixation methods were selected for internal fixation treatment according to different fracture types.The operation time, blood loss, preoperative and postoperative displacement difference, fracture healing time and Rockwood scoring system were recorded. RESULTS: All patients were followed up for 12 to 24 months. There were no patients with infection or loss of reduction after the operation. Three patients had internal fixation failure after operation, and the internal fixation device was removed. Results The operation time was 30 to 65 min, and the blood loss was 15 to 40 ml. No important nerves, blood vessels, or organs were damaged. The imaging healing time was 3 to 6 months. According to the Rockwood functional score, the total score was (13.50±1.86), pain (2.57±0.50), range of motion (2.78±0.41), muscle strength (2.93±0.28), restricted daily activity (2.85±0.35), subjective results (2.63±0.61);the results were excellent in 20 cases, good in 3 cases, fair in 1 case. CONCLUSION: Proximal clavicular fracture is a type of fracture with low incidence. According to different fracture types, different internal fixation methods and treatment methods can be selected, and satisfactory surgical results can be achieved.

[Finite element analysis of PMMA bone cement reinforced screw plate fixation for osteoporotic proximal humeral fracture].

OBJECTIVE: With the help of finite element analysis, to explore the effect of proximal humeral bone cement enhanced screw plate fixation on the stability of internal fixation of osteoporotic proximal humeral fracture. METHODS: The digital model of unstable proximal humeral fracture with metaphyseal bone defect was made, and the finite element models of proximal humeral fracture bone cement enhanced screw plate fixation and common screw plate fixation were established respectively. The stress of cancellous bone around the screw, the overall stiffness, the maximum stress of the plate and the maximum stress of the screw were analyzed. RESULTS: The maximum stresses of cancellous bone around 6 screws at the head of proximal humeral with bone cement enhanced screw plate fixation were 1.07 MPa for No.1 nail, 0.43 MPa for No.2 nail, 1.16 MPa for No.3 nail, 0.34 MPa for No.4 nail, 1.99 MPa for No.5 nail and 1.57 MPa for No.6 nail. These with common screw plate fixation were:2.68 MPa for No.1 nail, 0.67 MPa for No.2 nail, 4.37 MPa for No.3 nail, 0.75 MPa for No.4 nail, 3.30 MPa for No.5 nail and 2.47 MPa for No.6 nail. Overall stiffness of the two models is 448 N/mm for bone cement structure and 434 N/mm for common structure. The maximum stress of plate appears in the joint hole:701MPa for bone cement structure and 42 0MPa for common structure. The maximum stress of screws appeared at the tail end of No.4 nail:284 MPa for bone cement structure and 240.8 MPa for common structure. CONCLUSION: Through finite element analysis, it is proved that the proximal humerus bone cement enhanced screw plate fixation of osteoporotic proximal humeral fracture can effectively reduce the stress of cancellous bone around the screw and enhance the initial stability after fracture operation, thus preventing from penetrating out and humeral head collapsing.

[CT imaging measurement of sacral related anatomical parameters].

OBJECTIVE: To investigate the CT measurement of sacral anatomical parameters and understand the safe nail placement channel of DenisⅠ area with a new sacral butterfly plate. METHODS: The CT data of 101 normal adult sacrum from January 2020 to June 2020 were retrospectively analyzed, including 49 females and 52 males, aged(49.11±15.02) years old. Firstly, the three-dimensional model of sacrum was reconstruct, the three-dimensional model according to the plane was re segment to be measured, and data measurement and statistical analysis were carried out. RESULTS: The vertical distance from the lower edge of superior sacral articular process to the lower edge of S2 posterior sacral foramen was (42.55±4.73) mm;The horizontal distance from the lateral sacral crest of S1, S2 and S3 hole plane to the sacroiliac joint surface was (19.09±3.07) mm, (15.34±2.69) mm and (8.29±2.48) mm respectively;The plane of S1 hole moves forward from the lateral sacral ridge, the inner and outer angles are (7.49±7.49)° and (24.07±4.89)° respectively;The inside and outside angles of S2 hole plane are (-3.10±8.95)° and (24.95±5.74)° respectively. There were significant differences between different genders except S1 horizontal distance and S1 medial angle, and there was no correlation between age and all data. CONCLUSION: The new sacral butterfly plate has enough safe nail placement range in DenisⅠ area;There are differences in sacral morphology among adults. The differences are mainly related to gender but not age.

miR­204­5p inhibits the occurrence and development of osteoarthritis by targeting Runx2.

One of the hallmarks of osteoarthritis (OA) development is endochondral ossification, in which Runt­related transcription factor­2 (Runx2) is aberrantly expressed. Runx2 was previously identified to be regulated by microRNA­204­5p (miR­204­5p). The aim of the present study was to investigate the potential function of miR­204­5p regulating Runx2 during the development of OA and the underlying molecular mechanism. The expression levels of miR­204­5p and Runx2 were determined in tissue specimens. Rat OA models were established by transecting the anterior and posterior cruciate ligaments and removing the meniscus. Rats were treated with miR­204­5p agomir and miR­204­5p negative control (NC). All in vitro experiments were performed using rat primary chondrocytes and the SW­1353 human bone chondrosarcoma cell line. It was identified that the expression of miR­204­5p was significantly decreased, whereas Runx2 was significantly increased, in human OA tissues compared with in non­OA tissues, and levels were inversely associated with each other in primary chondrocytes and chondrosarcoma cells. Overexpression of miR­204­5p decreased the proliferation of chondrocytes and SW­1353 cells. Using a luciferase reporter assay, Runx2 was identified to be a direct target of miR­204­5p in chondrocytes and overexpressed miR­204­5p altered the expression of collagens II, X and matrix metalloproteinase (MMP)­1 and MMP­13 in primary chondrocytes and SW­1353 cells. Histological analysis revealed that miR­204­5p treatment ameliorated the OA­like phenotype that is reflected by assessment of cartilage thickness and Mankin's score. Runx2 expression was gradually increased as the rats increased in age. At 10 weeks of miR­204­5p agomir treatment, altered expression levels of collagens II and X, cartilage oligomeric matrix protein fragment, aggrecan, MMP­1 and MMP­13 were observed in the treatment group compared with the NC group. In conclusion, the results of the present study indicated that miR­204­5p decreases chondrocyte proliferation and ameliorates the OA­like phenotype in rats with surgically induced OA by targeting Runx2.

TUG1 promotes osteosarcoma tumorigenesis by upregulating EZH2 expression via miR-144-3p.

lncRNA-TUG1 (Taurine upregulated 1) is up-regulated and highly correlated with poor prognosis and disease status in osteosarcoma. TUG1 knockdown inhibits osteosarcoma cell proliferation, migration and invasion, and promotes apoptosis. However, its mechanism of action has not been well addressed. Growing evidence documented that lncRNA works as competing endogenous (ce)RNAs to modulate the expression and biological functions of miRNA. As a putative combining target of TUG1, miR-144-3p has been associated with the progress of osteosarcoma. To verify whether TUG1 functions through regulating miR-144-3p, the expression levels of TUG1 and miR-144-3p in osteosarcoma tissues and cell lines were determined. TUG1 was upregulated in osteosarcoma tissues and cell lines, and negatively correlated with miR-144-3p. TUG1 knockdown induced miR-144-3p expression in MG63 and U2OS cell lines. Results from dual luciferase reporter assay, RNA-binding protein immuno-precipitation (RIP) and applied biotin-avidin pull-down system confirmed TUG1 regulated miR-144-3p expression through direct binding. EZH2, a verified target of miR-144-3p was upregulated in osteosarcoma tissues and negatively correlated with miR-144-3p. EZH2 was negatively regulated by miR-144-3p and positively regulated by TUG1. Gain-and loss-of-function experiments were performed to analyze the role of TUG1, miR-144-3p and EZH2 in the migration and EMT of osteosarcoma cells. EZH2 over-expression partly abolished TUG1 knockdown or miR-144-3p overexpression induced inhibition of migration and EMT in osteosarcoma cells. In addition, TUG1 knockdown represses the activation of Wnt/ß-catenin pathway, which was reversed by EZH2 over-expression. The activator of Wnt/ß-catenin pathway LiCl could partially block the TUG1-knockdown induced osteosarcoma cell migration and EMT inhibition. In conclusion, our results showed that TUG1 plays an important role in osteosarcoma development through miRNA-144-3p/EZH2/Wnt/ß-catenin pathway.

Synthesis of higher alcohols over highly dispersed Cu-Fe based catalysts derived from layered double hydroxides.

Highly dispersed Cu-Fe based catalysts with Fe/Cu molar ratios ranging from 0.2 to 1 were prepared via thermal decomposition of layered double hydroxides (LDHs) precursors and tested for higher alcohol synthesis (HAS) via CO hydrogenation. The catalysts were characterized using different techniques such as XRD, TEM, XPS, and H2-TPR. It was demonstrated that the Cu and Fe ions were highly dispersed in the brucite-like layers of the LDHs. With increased Fe/Cu atomic ratio, the tetrahedrally coordinated Cu ion content, Cu reduction temperatures, and the spacing of layers initially increase until the Fe/Cu ratio reaches 0.5 and then decrease. In addition to the catalytic evaluation for CO hydrogenation and catalyst characterization, the relationships between the physical-chemical properties of the catalysts and their catalytic performances were also investigated. It was also found that the alcohols/hydrocarbons ratios correlate linearly with the tetrahedrally coordinated Cu ion content. Moreover, higher reduction temperatures of Cu species as well as larger spacing between the layers in the catalyst are favorable for the synthesis of alcohols. The incorporation of a suitable amount of Fe is beneficial for the production of higher alcohols, with the best catalytic performance (alcohol selectivity of 20.77% and C2+ alcohol selectivity of 48.06%) obtained from a Fe/Cu atomic ratio of 0.5.