BACKGROUND:The reasonable implantation range of femoral prosthesis in unicompartmental knee arthroplasty in patients with osteoporosis has not been investigated,and previous studies have often been based on unicompartmental knee arthroplasty models in normal bone,with fewer mechanical studies in models with non-normal bone.Complications after unicompartmental knee arthroplasty have been shown to be highly associated with osteoporosis. OBJECTIVE:To analyze the biomechanical effects of the coronal inclination of the Sled fixed platform femoral prosthesis on unicompartmental knee arthroplasty in patients with osteoporosis and to find the correlation between osteoporosis and mid-and long-term complications after unicompartmental knee arthroplasty. METHODS:Based on the digital imaging technology to obtain the data of the knee joint and prosthesis,a normal bone knee model is then created by using specialized software such as Mimics and Geomagic studio.Based on a validated normal bone knee model,an osteoporotic knee model was created by changing the material parameters.Totally 14 unicompartmental knee arthroplasty finite element models were created using Sled fixed platform femoral prosthesis:standard position(0°),varus and valgus angles:3°,6°,9° in the normal bone and osteoporosis groups.Stress changes on the surface of polyethylene liner,cancellous bone under tibial prosthesis,and cortical bone were calculated and analyzed in all unicompartmental knee arthroplasty models. RESULTS AND CONCLUSION:(1)In the osteoporotic models,the high stress values of the polyethylene liner surface and the cancellous bone under the tibial prosthesis increased with the increase of the tilt angle of the femoral prosthesis,and the high stress values of the cortical bone surface under the tibial prosthesis increased with the increase of the prosthesis valgus angles and decreased with the increase of the varus angles.(2)For the polyethylene liner surface as well as the subcortical bone surface of the tibial prosthesis,the high stress values of the models for each inclination angle in the osteoporosis group were greater than those of the corresponding models in the normal bone group.For the surface of the cancellous bone under the tibial prosthesis,the high stress values of the tilt angle models of the osteoporosis groups were smaller than those of the normal bone groups.(3)Osteoporosis may cause biomechanical abnormalities in the internal structures of the knee after unicondylar replacement,increasing the potential risk of postoperative aseptic loosening of the prosthesis and periprosthetic fractures.Varus and valgus of the femoral prosthesis in the coronal plane should be avoided as much as possible when performing medial unicompartmental knee arthroplasty with a Sled fixation platform in osteoporotic knees.

BACKGROUND:Ferroptosis is strongly associated with the occurrence and progression of osteoarthritis,but the specific characteristic genes and regulatory mechanisms are not known. OBJECTIVE:To identify osteoarthritis ferroptosis signature genes and immune infiltration analysis using the WGCNA and various machine learning methods. METHODS:The osteoarthritis dataset was downloaded from the GEO database and ferroptosis-related genes were obtained from the FerrDb website.R language was used to batch correct the osteoarthritis dataset,extract osteoarthritis ferroptosis genes and perform differential analysis,analyze differentially expressed genes for GO function and KEGG signaling pathway.WGCNA analysis and machine learning(random forest,LASSO regression,and SVM-RFE analysis)were also used to screen osteoarthritis ferroptosis signature genes.The in vitro cell experiments were performed to divide chondrocytes into normal and osteoarthritis model groups.The dataset and qPCR were used to verify expression and correlate immune infiltration analysis. RESULTS AND CONCLUSION:(1)12 548 osteoarthritis genes were obtained by batch correction and PCA analysis,while 484 ferroptosis genes were obtained,resulting in 24 differentially expressed genes of osteoarthritis ferroptosis.(2)GO analysis mainly involved biological processes such as response to oxidative stress and response to organophosphorus,cellular components such as apical and apical plasma membranes,and molecular functions such as heme binding and tetrapyrrole binding.(3)KEGG analysis exhibited that differentially expressed genes of osteoarthritis ferroptosis were related to signaling pathways such as the interleukin 17 signaling pathway and tumor necrosis factor signaling pathway.(4)After using WGCNA analysis and machine learning screening,we obtained the characteristic gene KLF2.After validation by gene microarray,we found that the gene expression of KLF2 was higher in the test group than in the control group in the meniscus(P=0.000 14).(5)In vitro chondrocyte assay showed that type Ⅱ collagen and KLF2 expression was lower in the osteoarthritis group than in the control group in chondrocytes(P<0.05),while in osteoarthritis ferroptosis,mast cells activated was closely correlated with dendritic cells(r=0.99);KLF2 was closely correlated with natural killer cells(r=-1,P=0.017)and T cells follicular helper(r=-1,P=0.017).(6)The findings indicate that using WGCNA analysis and machine learning methods confirmed that KLF2 can be a characteristic gene for osteoarthritis ferroptosis and may improve osteoarthritis ferroptosis by interfering with KLF2.

BACKGROUND:Hypoxia is strongly associated with the development and progression of osteoarthritic chondrocyte injury,but the specific targets and regulatory mechanisms are unclear. OBJECTIVE:A machine learning approach was used to identify KDEL(Lys-Asp-Glu-Leu)receptor 3(KDELR3)as a characteristic gene for osteoarthritis hypoxia and immune infiltration analysis,to provide new ideas and methods for the treatment of osteoarthritis. METHODS:The osteoarthritis-related datasets were downloaded from the GEO database and the GSEA website to obtain hypoxia-related genes.The osteoarthritis datasets were batch-corrected and immune infiltration analyzed using R language,and osteoarthritis hypoxia genes were extracted for differential analysis.Differentially expressed genes were analyzed for GO function and KEGG signaling pathway.Weighted correlation network analysis(WGCNA)and machine learning were also used to screen osteoarthritis hypoxia signature genes,and in vitro cellular experiments were performed to validate expression and correlate immune infiltration analysis using the datasets and qPCR. RESULTS AND CONCLUSION:(1)8492 osteoarthritis genes were obtained by batch correction and principal component analysis,mainly strongly associated with immune cells such as Macrophages M2 and Mast cells resting;200 hypoxia genes were also obtained,resulting in 41 osteoarthritis hypoxia differentially expressed genes.(2)GO analysis involved mainly biological processes such as response to nutrient levels and glucocorticoids;cellular components such as lysosomal lumen and Golgi lumen;and molecular functions such as 14-3-3 protein binding and DNA-binding transcriptional activator activity.(3)KEGG analysis of osteoarthritis hypoxia differentially expressed genes was associated with signaling pathways such as PI3K-Akt,FoxO,and microRNAs in cancer.(4)The characteristic gene KDELR3 was obtained after using WGCNA analysis and machine learning screening.(5)The gene expression of KDELR3 was found to be higher in the test group than in the control group in the synovium(P=0.014)but lower in the meniscus(P=0.024)after validation by gene microarray.(6)In vitro chondrocyte assay showed that the expression of KDELR3 was higher in cartilage than in the control group(P=0.005),while KDELR3 was closely associated with Macrophages M0(P=0.014)and T cells follicular helper(P=0.014).Using a machine learning approach,we confirmed that KDELR3 can be used as a hypoxic signature gene for osteoarthritis and may intervene in osteoarthritis pathogenesis by improving hypoxia,expecting to provide a new direction for better treatment of osteoarthritis.

Objective To investigate the mechanism of inducing macrophage polarization induced by acupoint effect of electroacupuncture to promote the repair of acute skeletal muscle injury.Methods 45 SD rats were randomly divided into blank group,model group,electroacupuncture group(EA group),sodium chrominate group (DSCG group) and electroacupuncture+sodium chrominate group (hereinafter referred to as EA+DSCG group),with 9 rats in each group. The rats in the EA group and the EA+DSCG group were subjected to EA intervention at the right "Chengshan" (BL57) and "Yanglingquan"(GB34),with a frequency of 2 Hz/100 Hz. The gait changes of rats were recorded by animal gait analyzer. The morphological changes of the right gastrocnemius were observed by HE staining. The changes of mast cell aggregation and degranulation in local skin muscles of "chengshan" point were observed by toluidine blue staining. The expressions of Pax7,MyoD and skin mast cells and 5-HT in the right gastrocnemius were detected by immunofluorescence method. The positive expressions of CD68 and CD206 in right gastrocnemius macrophage was observed by immunohistochemical staining.Results Compared with blank group,the wiggle time of the right hind leg in model group and DSCG group increased,stride length decreased,HE staining showed inflammatory cell infiltration,myocyte enlargement,degeneration and necrosis. The degranulation rate of local skin mast cells in "Chengshan" (BL57) area increased,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD,CD68 and CD206 increased (P<0.05). Compared with model group,the wiggle time of the right hind leg in EA group and EA+DSCG group decreased,stride length increased,HE staining showed that inflammatory cell infiltration was reduced,muscle cells were uniform in size and arranged neatly. Mast cell degranulation rate increased significantly in EA group,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased (P<0.05). Compared with EA+DSCG group,the degranulation rate of mast cells and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased in EA group (P<0.05). Conclusion EA "Chengshan" (BL57) and "Yanglingquan" (GB34) can stimulate acupuncture points to locally induce mast cell degranulation,promote the polarization of macrophages,and then activate muscle satellite cells to play the regulatory process of repairing skeletal muscle injury.

Objective This study aims to elucidate the structure-activity domain of LBP1C-2 targeting Kvβ.2 through an exploration of the structure-activity relationship.This study may also provide the scientific basis for the development of drug candidate with anti-early-onset dementia activity.Methods After partial acid hydrolysis,various structural fragments were obtained and subjected to monosaccharide composition and molecular weight analysis.Potential target proteins were selected using a protein chip,followed by validation of the targeting specificity of each structural fragment using surface plasmon resonance(SPR)technology.Results Through high-throughput screening using the HuProtTM human protein array,potential target protein Kvβ.2 was identified for LBP1C-2.SPR experiments revealed a strong binding affinity between LBP1C-2 and Kvβ.2 protein,with a binding constant(KD)of 1.9×10-7 M.The various structural fragments of LBP1C-2 exhibited different binding strengths with the target protein Kvβ.2.Among them,the segment LBP1C-2-1I(18.1 k Da)with a molar ratio of rhamose to galecturonic acid of 1:1 showed a binding strength to Kvβ.2 similar to that of the polysaccharide LBP1C-2,with a KD of approximately 3.3×10-7 M.Structural analysis indicates that the structure of LBP1C-2-1I contains 1,2-linked Rha and 1,4-linked GalA which are alternatively linked.The acid-hydrolyzed extracellular portion corresponding to this segment,LBP1C-2-1O may also bind to Kvβ.2.However,compared to other segments,it demonstrated a higher tendency to dissociate from the protein.Knockdown of the KCNAB2 gene(Kvβ.2)in BV2 cells inhibited the uptake of Aβ in BV2 cells,suggesting that protein Kvβ.2 may be a functional protein in the development of Alzheimer's disease.Conclusion LBP1C-2-1I has been identified as the primary active domain through which LBP1C-2 targets Kvβ.2.This suggests that the active domain of LBP1C-2 predominantly resides on the main chain rather than the side chain.This study provides crucial insights for a deeper understanding of the anti-early-onset dementia activity of LBP1C-2 and lays an experimental foundation for the design and development of targeted drugs for anti-early-onset dementia based on Lycium barbarum polysaccharides.

Acute liver failure(ALF)is one of the most critical liver diseases in clinical practice and seriously affects the life and health of Chinese people.Due to its high morbidity and mortality rates,unclear pathogenesis,and limited treatment methods,ALF has become a major problem that needs to be solved urgently in the field of liver diseases.In recent years,more and more studies have shown that endoplasmic reticulum stress is a key biological process in the progression of ALF,and the IRE1α/TRAF2/JNK pathway,as a part of endoplasmic reticulum stress signaling,plays a role in amplifying inflammatory response,promoting hepatocyte apoptosis,and inhibiting liver regeneration ability during the progression of diseases.As a traditional treasure of China,traditional Chinese medicine has become a research hotspot in search for effective prevention and treatment drugs for ALF from monomers of Chinese herbs.This article elaborates on the mechanism of action of the IRE1α/TRAF2/JNK pathway in the progression of ALF and summarizes the potential value of several monomers of Chinese herbs in regulating this pathway,such as salidroside,Fructus Broussonetiae,Fructus Psoraleae+Schisandra chinensis,baicalein,genipin,kaempferol,resveratrol,sea buckthorn polysaccharide extract,and luteol,in order to provide a reference for further research and clinical practice of ALF.

Objective:To explore influencing factors of the self-reported brief life quality satisfaction score(Brief-QoL) in patients with acromegaly and understand the persistent low Brief-QoL scores in cases achieving biochemical remission.Methods:This study included 836 acromegaly patients who were hospitalized at Peking Union Medical College Hospital between January 2012 and December 2020. We retrospectively examined how clinical characteristics, biochemical parameters, comorbidities, and symptoms influenced Brief-QoL. Among patients who achieved biochemical remission, differences in clinical symptoms and comorbidities were analyzed between the high and low quality of life groups.Results:Patients with well-controlled biochemical indicators at the last follow-up had generally high Brief-QoL. However, patients with symptoms such as headaches (47.8% in the low-score group vs 14.9% in the high-score group, P<0.001) and joint pain (69.6% in the low-score group vs 19.0% in the high-score group, P<0.001) had low Brief-QoL despite biochemical remission. Receiving combined treatment(52.4% in the low-score group vs 27.5% in the high-score group, P=0.030) and having comorbid diabetes or hyperlipidemia were significant factors leading to decreased quality of life. Conclusion:Brief-QoL is suitable for follow-up of outpatient patients. Early identification of factors affecting quality of life and timely intervention can facilitate the realization of standardized management.

PURPOSE: This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury. METHODS: AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis. RESULTS: The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11. CONCLUSION EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.
Humans ; Rats ; Animals ; Alveolar Epithelial Cells ; Lung ; Lung Injury ; Cell Movement/physiology*

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.
Male ; Mice ; Animals ; Testis/metabolism* ; Ferroptosis ; Semen ; Oxidative Stress

Objective:To investigate the efficacy of open exploration, ulnar osteotomy and annular ligament reduction (three-in-one surgery) in the treatment of chronic Monteggia fracture in children.Methods:The data were analyzed retrospectively of the 35 children with chronic Monteggia fracture who had been admitted to Department of Pediatric Orthopaedics, Tianjin University from June 2017 to September 2021. There were 22 boys and 13 girls, and 19 left and 16 right sides, with an age of (6.8±2.5) years. Anterolateral dislocation of the radial head occurred in 30 cases and anterolateral dislocation in 5 ones. The time from injury to operation was (17.9±9.9) months. All patients were treated with three-in-one surgery. The elbow flexion and extension, forearm rotation and The Hospital for Special Surgery (HSS) elbow score were measured and compared in all patients at 12 months after operation. Their complications were also recorded.Results:All children were followed up for 12 months. The osteotomy ends of the ulna achieved bony union 1.5 to 4.0 months after operation. The elbow extension (-1.0°±5.9°) and flexion (128.5°±4.9°) at 12 months after operation were significantly improved compared with those before operation (-9.3°±18.0° and 108.4°±17.3°) ( P<0.05). The forearm pronation (61.5°±19.4°) at 12 months after operation was significantly limited compared with that before operation (72.7°±22.4°) ( P<0.05). There was no significant difference between the forearm supination (86.7°±4.5°) at 12 months after operation and that before operation (81.0°±17.4°) ( P>0.05). The HSS elbow score at 12 months after operation (93.5±5.2) was significantly higher than that (80.6±9.3) before operation ( P<0.05). The efficacy evaluated by the HSS elbow score at 12 months after operation was excellent in 21 cases, good in 12 cases, and fair in 2 cases, giving an excellent and good rate of 94.3% (33/35). Postoperative re-subluxation was observed in one patient. Conclusion:Open exploration, ulnar osteotomy and annular ligament reduction are a safe and effective three-in-one surgery for chronic Monteggia fracture in children, because it may lead to significantly improved elbow flexion and extension after operation, though the forearm pronation may be limited.