Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis.

OBJECTIVE: Ferroptosis has been reported to play a role in rheumatoid arthritis (RA). Sulfasalazine, a common clinical treatment for ankylosing spondylitis, also exerts pathological influence on the progression of rheumatoid arthritis including the induced ferroptosis of fibroblast-like synoviocytes (FLSs), which result in the perturbated downstream signaling and the development of RA. The aim of this study was to investigate the underlying mechanism so as to provide novel insight for the treatment of RA. METHODS: CCK-8 and Western blotting were used to assess the effect of sulfasalazine on FLSs. A collagen-induced arthritis mouse model was constructed by the injection of collagen and Freund's adjuvant, and then, mice were treated with sulfasalazine from day 21 after modeling. The synovium was extracted and ferroptosis was assessed by Western blotting and immunofluorescence staining. RESULTS: The results revealed that sulfasalazine promotes ferroptosis. Compared with the control group, the expression levels of ferroptosis-related proteins such as glutathione peroxidase 4, ferritin heavy chain 1, and solute carrier family 7, member 11 (SLC7A11) were lower in the experimental group. Furthermore, deferoxamine inhibited ferroptosis induced by sulfasalazine. Sulfasalazine-promoted ferroptosis was related to a decrease in ERK1/2 and the increase of P53. CONCLUSIONS: Sulfasalazine promoted ferroptosis of FLSs in rheumatoid arthritis, and the PI3K-AKT-ERK1/2 pathway and P53-SLC7A11 pathway play an important role in this process.

Gene expression of Postn and FGF7 in canine chordae tendineae and their effects on flexor tenocyte biology.

Chordae tendineae, referred to as heart tendinous cords, act as tendons connecting the papillary muscles to the valves in the heart. Their role is analogous to tendons in the musculoskeletal system. Despite being exposed to millions of cyclic tensile stretches over a human's lifetime, chordae tendineae rarely suffer from overuse injuries. On the other hand, musculoskeletal tendinopathy is very common and remains challenging in clinical treatment. The objective of this study was to investigate the mechanism behind the remarkable durability and resistance to overuse injuries of chordae tendineae, as well as to explore their effects on flexor tenocyte biology. The messenger RNA expression profiles of chordae tendineae were analyzed using RNA sequencing and verified by quantitative reverse transcription polymerase chain reaction  and immunohistochemistry. Interestingly, we found that periostin (Postn) and fibroblast growth factor 7 (FGF7) were expressed at significantly higher levels in chordae tendineae, compared to flexor tendons. We further treated flexor tenocytes in vitro with periostin and FGF7 to examine their effects on the proliferation, migration, apoptosis, and tendon-related gene expression of flexor tenocytes. The results displayed enhanced cell proliferation ability at an early stage and an antiapoptotic effect on tenocytes, while treated with periostin and/or FGF7 proteins. Furthermore, there was a trend of promoted tenocyte migration capability. These findings indicated that Postn and FGF7 may represent novel cytokines to target flexor tendon healing. Clinical significance: The preliminary discovery leads to a novel idea for treating tendinopathy in the musculoskeletal system using specific molecules identified from chordae tendineae.

Low albumin-to-fibrinogen ratio predicts adverse clinical outcomes after primary total joint arthroplasty: A retrospective observational investigation.

Nutritional markers for adverse clinical outcomes following total joint arthroplasty (TJA) remain controversial. This study attempted to explore the validity of the albumin-to-fibrinogen ratio (AFR) in nutritional assessment and assess its predictive value for adverse postoperative outcomes in patients receiving TJA. 2137 patients who underwent primary TJA between January 2016 and June 2021 were screened. We performed receiver operating characteristic curves and area under the curve (AUC) to assess predictive value and establish optimal thresholds. Multivariate regression models were then used to assess potential associations between AFR and adverse postoperative outcomes. AFR might predict postoperative deep surgical site infections (AUC = 0.699, P = .023). The optimal threshold for wound complications, determined by the Youden index, was 12.96. Compared with patients with reduced AFR, patients with high AFR exhibited an enhanced risk of adverse postoperative outcomes (adjusted OR: 4.010-8.832, all P < .05). Using multivariate Cox regression analysis, we further confirmed a higher risk of adverse postoperative outcomes in patients with low AFR (adjusted HR: 3.733-7.335, all P < .05). Reduced preoperative AFR markedly enhanced adverse postoperative outcomes. Hence, AFR may serve as a potential biomarker for nutritional assessment, and may predict postoperative wound complications following primary TJA.

Nutritional Risk Screening 2002 predicts surgical outcomes in 1532 patients undergoing total joint arthroplasty: A retrospective cohort study.

BACKGROUND: Limited information exists about the predictive effect of Nutritional Risk Screening (NRS) 2002 on orthopedic surgery. The aim of the present study is to explore the role of NRS 2002 in postoperative complications and resource utilization in patients with total joint arthroplasty (TJA). METHODS: We retrospectively collected the demographics and surgical results of nearly 2000 TJA patients admitted from 2016 to 2020 and assessed the differences in short- and long-term complications and resource utilization parameters. Multivariate linear, logistic regression, and subgroup analysis were subsequently used to control for potential confounders. Survival analysis was performed to further verify the cumulative incidence of postoperative complications. RESULTS: We identified 1532 patients receiving TJA, 8.7% of which were at nutrition risk (NRS 2002 score ≥3 out of 7). Preoperative nutrition risk was associated with an increased risk of systemic complications, incisional complications, surgical site infection (SSI), incisional SSI, periprosthetic joint infection, dislocation, and periprosthetic fracture after TJA (odds ratio [OR], 3.62-31.99; all P < 0.05). Preoperative nutrition risk was further associated with an increased risk of cardiac complications, respiratory complications, urinary complications, and arthroplasty-related reoperation (OR, 3.16-12.29; all P < 0.01). Moreover, preoperative nutrition risk was associated with increased costs and length of stay, and increased risk of unplanned intensive care unit admission, arthroplasty-related readmission, infection-related readmission, and SSI-related readmission. CONCLUSIONS: NRS 2002 is associated with an elevated risk of postoperative complications and increased resource utilization, following TJA. Thus, routine screening is recommended to identify nutrition risk statuses of patients undergoing elective TJA.

Theaflavin-3,3'-Digallate Inhibits Erastin-Induced Chondrocytes Ferroptosis via the Nrf2/GPX4 Signaling Pathway in Osteoarthritis.

There is evidence that osteoarthritis (OA) is associated with ferroptosis which is a kind of lipid peroxidation-related cell death. Theaflavin-3,3'-digallate(TF3), a polyphenol compound extracted from black tea, possesses antioxidative and anti-inflammatory properties, but its effects on chondrocyte ferroptosis in osteoarthritis (OA) remain unclear. Our present study aims at exploring the protective role and underlying mechanisms of TF3 against erastin-induced chondrocyte ferroptosis in OA. In human primary chondrocytes treated with erastin alone or combined with different doses of TF3, cell viability was assessed by MTS. Ferroptosis-related proteins, including Gpx4, HO-1, and FTH1, were detected by western blot. The levels of lipid peroxidation and Fe2+ were determined by fluorescence staining. Meanwhile, the change of related proteins in the Nrf2/Gpx4 signaling pathway was determined by western blot. siRNA-mediated Nrf2 knockdown and the Gpx4 inhibitor RSL3 were used to explore molecular mechanisms for TF3-induced ferroptosis in OA chondrocyte. The magnetic resonance imaging (MRI), HE staining, Masson's staining, and immunohistochemistry were used to evaluate articular cartilage damages in the rat OA model. The results showed that Gpx4 expression was markedly downregulated in the chondrocytes of OA patients. TF3 reversed erastin-induced ferroptosis of human cultured chondrocytes, lipid ROS, and Fe2+ production in mitochondria. Moreover, the expression of Gpx4, HO-1, FTH1, and Nrf2 was markedly induced by TF3 in the erastin-treated chondrocytes. The antiferroptotic effect of TF3 was related to enhance Nrf2/Gpx4 signaling pathway. Finally, TF3 inhibited OA progression by alleviating in vivo cartilage damage related to chondrocyte ferroptosis. Thus, TF3 significantly inhibits chondrocyte ferroptosis by activating the Nrf2/Gpx4 signaling pathway, suggesting that TF3 serves as a potential therapeutic supplement for OA treatment.

Harmine Alleviates Titanium Particle-Induced Inflammatory Bone Destruction by Immunomodulatory Effect on the Macrophage Polarization and Subsequent Osteogenic Differentiation.

Peri-prosthetic osteolysis (PPO) and following aseptic loosening are regarded as the prime reasons for implant failure after joint replacement. Increasing evidence indicated that wear-debris-irritated inflammatory response and macrophage polarization state play essential roles in this osteolytic process. Harmine, a ß-carboline alkaloid primitively extracted from the Peganum harmala seeds, has been reported to have various pharmacological effects on monoamine oxidase action, insulin intake, vasodilatation and central nervous systems. However, the impact of harmine on debris-induced osteolysis has not been demonstrated, and whether harmine participates in regulating macrophage polarization and subsequent osteogenic differentiation in particle-irritated osteolysis remains unknown. In the present study, we investigated the effect of harmine on titanium (Ti) particle-induced osteolysis in vivo and in vitro. The results suggested harmine notably alleviated Ti particle-induced bone resorption in a murine PPO model. Harmine was also found to suppress the particle-induced inflammatory response and shift the polarization of macrophages from M1 phenotypes to M2 phenotypes in vivo and in vitro, which improved anti-inflammatory and bone-related cytokines levels. In the conditioned medium from Ti particle-stimulated murine macrophage RAW264.7 cells treated with harmine, the osteoblast differentiation ability of mouse pre-osteoblastic MC3T3-E1 cells was greatly increased. And we also provided evidences that the immunomodulatory capacity of harmine might be attributed to the inhibition of the c-Jun N-terminal kinase (JNK) in wear particle-treated macrophages. All the results strongly show that harmine might be a promising therapeutic agent to treat PPO.

Polysaccharide from Angelica sinensis attenuates SNP-induced apoptosis in osteoarthritis chondrocytes by inducing autophagy via the ERK1/2 pathway.

OBJECTIVE: Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism. METHOD: Human primary chondrocytes isolated from the articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3) II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localization, and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of the ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-methyladenine (3-MA), chloroquine (CQ), and a specific inhibitor of ERK1/2, SCH772984, were used to confirm the autophagic effect of ASP. RESULTS: The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocyte proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of the ERK1/2 pathway. CONCLUSION: ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP as a potential therapeutic supplementation for OA treatment.

The Effects of Interleukin-33 (IL-33) on Osteosarcoma Cell Viability, Apoptosis, and Epithelial-Mesenchymal Transition are Mediated Through the PI3K/AKT Pathway.

BACKGROUND Osteosarcoma is the most common primary tumor of bone. Interleukin-33 (IL-33) is a pro-inflammatory cytokine that also participates in tumor progression. This study aimed to investigate the role of IL-33 in human osteosarcoma cell viability, proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) in vitro and the molecular mechanisms involved. MATERIAL AND METHODS The normal osteoblast cell line, hFOB 1.19, and the human osteosarcoma cell lines SOSP-9607, SAOS2, MG63, and U2OS were studied. The expression of IL-33 mRNA and protein in human osteosarcoma cell lines were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. The effects of IL-33 on human osteosarcoma cell viability, apoptosis, EMT, and the signaling pathways were studied using the MTT assay, flow cytometry, qRT-PCR, and Western blot. RESULTS IL-33 was upregulated in human osteosarcoma cell lines, including U2OS cells. The use of an IL-33 gene plasmid promoted osteosarcoma cell viability, inhibited cell apoptosis, increased the expression of Bcl-2, and reduced the expression of Bax. IL-33 reduced the level of E-cadherin and increased the levels of N-cadherin and matrix metalloproteinase-9 (MMP-9) in osteosarcoma cells at the mRNA and protein level. The use of the IL-33 plasmid increased the protein expression levels of p-AKT and the p-AKT/AKT ratio in osteosarcoma cells, and IL-33 siRNA reversed these findings. CONCLUSIONS IL-33 was highly expressed in human osteosarcoma cells. Down-regulation of IL-33 reduced cell viability and EMT of osteosarcoma cells, and induced cell apoptosis through activation of the PI3K/AKT signaling pathway.

LncRNA LUADT1 regulates miR-34a/SIRT1 to participate in chondrocyte apoptosis.

It is known that miR-34a can promote the apoptosis of chondrocytes, which directly contribute to osteoarthritis (OA). Through bioinformatics analysis, we found that long noncoding RNA LUADT1 may interact with miR-34a. We, therefore, further investigate the interactions between them in osteoarthritis. We found that LUADT1 was downregulated, while miR-34a was upregulated in OA synovial fluid. Correlation analysis revealed no significant correlation between them. Overexpression experiment also revealed no significant effects of LUADT1 and miR-34a on the expression of each other. However, the dual-luciferase assay showed that LUADT1 and miR-34a can directly interact with each other. Moreover, LUADT1 overexpression led to the upregulation of SIRT1, which is a downstream target of miR-34a. Cell apoptosis showed that LUADT1 and SIRT1 overexpression led to decreased, while miR-34a led to increased apoptotic rates of chondrocytes. Therefore, LUADT1 regulates miR-34a/SIRT1 to participate in chondrocyte apoptosis.

Using the anterior capsule of the hip joint to protect the tensor fascia lata muscle during direct anterior total hip arthroplasty: a randomized prospective trial.

BACKGROUND: The direct anterior approach for total hip arthroplasty (THA) has specific advantages, but injury to the tensor fasciae lata muscle (TFLM) remains a concern. This injury in part negates some of the advantages of the intermuscular approach, because injury of the muscle fibers of the TFLM can lead to less satisfactory clinical results. Thus, in this study, we propose an intraoperative method to protect the TFLM and demonstrate its feasibility. METHODS: Fifty-six patients undergoing THA by the direct anterior approach were divided randomly into two groups. In group A, the TFLM was protected by an autogenous tissue "pad" created from the anterior capsule of the joint which protect the TFLM from direct contact with the retractors. In group B, the operation was carried out with no protection of the TFLM except the attempt by the surgeons to consciously avoid injury of the TFLM. We evaluated magnitude of changes in the muscle cross-sectional area (MSCA) and fatty atrophy (FA) by magnetic resonance imaging. The differences in blood hemoglobin and serum levels of myoglobin, lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were compared at different time, postoperatively. The Harris hip score, postoperative drainage volume and visual analogue scores (VAS) were compared between the two groups. RESULTS: LDH, CPK and myoglobin in group B were significantly higher than group A at 8, 24, and 48 h after the surgery. (p < 0.05) Compared to the group A, the decrease of hemoglobin in group B displayed significantly at 24 and 48 h after surgery. (P < 0.05) The significantly increased MSCA and FA of TFLM were demonstrated in group B. The PDV and VAS in group B were significantly higher than group A. (P < 0.05) The Harris score in group A was significantly higher than group B (P < 0.05) one month after surgery, but there was no significant difference six months later. CONCLUSIONS: Using the anterior capsule of the hip joint as an autogenous, protective capsular tissue pad to limit the trauma to the TFLM during a direct anterior approach to THA is an effective method to protect the TFLM and improve the clinical effect. TRIAL REGISTRATION: ChiCTR: ChiCTR1900025173. Retrospectively registered August 15, 2019.

FSTL1 promotes nitric oxide-induced chondrocyte apoptosis via activating the SAPK/JNK/caspase3 signaling pathway.

OBJECTIVE: Previous studies have shown that follistatin-like protein 1 (FSTL1) is elevated in the synovial fluid of osteoarthritis and is associated with disease activity. The experiment was performed to stuy the effect and mechanism of FSTL1 on chondrocyte apoptosis in osteoarthritis. DESIGN: After the isolation of human normal and osteoarthritis (OA) chondrocytes, the expression of FSTL1 was detected by Q-PCR and western blot analyses. Chondrocytes were pre-transfected with FSTL1 overexpression plasmids then treated with SNP, and chondrocyte viability and apoptosis levels were detected by MTS and flow cytometry, respectively. Cartilage matrix gene expression was measured by Q-PCR and signal pathway-related proteins were assessed by western blot. RESULTS: The expression of FSTL1 in OA chondrocytes was markedly up-regulated compared with normal human chondrocytes (P < 0.05). The apoptosis rate of chondrocytes in the FSTL1 overexpression groups was highly elevated in the comparison with the negative control groups (P < 0.05). Additionally, FSTL1 potentiated protein abundances of MMP1, MMP3, MMP-9, and Bax as well as reduced Coll2a1 and Aggrecan and Bcl-2 expression. Furthermore, western blot results showed that the SAPK/JNK/Caspase3 signal pathway was significantly activated and the Ac-DEVD-FMK impaired FSTL1 induced chondrocyte apoptosis. CONCLUSION: FSTL1 promoted SNP-induced chondrocytes apoptosis by activating the SAPK/JNK/Caspase3 signal pathway.

The effect of different cross-linking conditions of EDC/NHS on type II collagen scaffolds: an in vitro evaluation.

The purpose of this paper is to analyze the properties of porcine cartilage type II collagen scaffolds crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxy-succinamide (EDC/NHS) under different conditions. The porous EDC/NHS-crosslinked scaffolds were obtained through a two-step freeze-drying process. To determine the optimal crosslinking condition, we used different solvents and various crosslinking temperatures to prepare the scaffolds. Three crosslinking solutions were prepared with different solvents, photographs were taken with a flash in the darkroom, and light transmission was observed. Type II collagen was crosslinked on a horizontal shaker at a speed of 60 r/min according to the above grouping conditions, and then the structural change of the scaffold in each group was observed. To investigate the swelling ratio and the in vitro degradation of the collagen scaffold, tests were also carried out by immersion of the scaffolds in a PBS solution and digestion in type II collagenase, respectively. The influence of the scaffolds on the proliferation of chondrocytes was assessed by the methyl thiazolyl tetrazolium colorimetric assay. The morphology of the crosslinked scaffolds cocultured with chondrocytes was characterized by a scanning electron microscope. The results proved that 75% alcohol and a crosslinking temperature of 37 °C are recommended. Collagen fibrils are more densely packed after crosslinking with EDC/NHS and have a more uniform structure than that of noncrosslinked ones. The EDC-crosslinked scaffolds possessed excellent mechanical property and biocompatibility.

Dissection and ligation of the lateral circumflex femoral artery is not necessary when using the direct anterior approach for total hip arthroplasty.

BACKGROUND: Branches of the lateral circumflex femoral artery (LCFA) stretch across the surgical field during a direct anterior total hip arthroplasty. It is an anatomical marker in direct anterior approach. As an important vessel around the hip joint, this vessel was ligated in most situations. Although ligation of the vascular pedicle of the LCFA is a common, traditional procedure used to decrease bleeding, the ligation of the pedicle of the vessel is tedious and time-consuming. AIM: To explore whether this ligation is truly necessary in a direct anterior approach to total hip arthroplasty. METHODS: This single-center, single-surgeon, prospective study was performed to compare patients' bleeding undergoing ligation of the branches of the LCFA pedicle (group A) vs those treated with electrocautery from the branches of the LCFA (group B). In both groups, the pedicles were identified in the intermuscular plane between the tensor fasciae lata and the rectus femoris muscles. In group A, the pedicles were ligated with a silk ligature. In group B, the branches coming off the LCFA were controlled with electrocautery. We compared preoperative vs postoperative changes in blood hemoglobin levels, intraoperative blood loss, operative time, rates of transfusion, re-bleeding, and hematoma between the two groups. RESULTS: The reduction of hemoglobin in group A was 20.9 ± 7.0, and in group B it was 21.2 ± 4.9. There was no statistically significant difference between the two groups (P > 0.05). The actual calculated blood loss in group A was 784 ± 125 mL, and in group B it was 722 ± 153 mL. There was a trend in group A having more blood loss (P = 0.078). The estimated blood loss in group A was 344 ± 88 mL, and in group B it was 346 ± 73 mL. There was no statistically significant difference between the two groups (P = 0.883). In addition, there were no significant differences in the rates of postoperative transfusion (10% vs 6.7%, P > 0.05), postoperative hematomas (6.7% vs 13.3%, P > 0.05), or re-bleeding (13.3% vs 20%, P > 0.05) between the two groups. CONCLUSION: Ligation of the pedicle of the LCFA has no advantage in preventing or decreasing bleeding during or after a total hip arthroplasty using the direct anterior approach. Ligation of the pedicle of the vessel is a cumbersome, unnecessary procedure and can be replaced by electrocautery control of the branches off this artery that course through the surgical field.

Soft tissue restrictors of femoral elevation in direct anterior approach-an anatomic study.

BACKGROUND: With the patient in a constant supine position, elevation of the femur in THA (DAA) provides a more intuitive and conducive location of the acetabulum for the correct placement of the acetabular prosthesis, but elevation of the femur for broaching becomes more challenging. The purpose of this study is to analyze the restriction of the ischiofemoral ligament and short external rotation muscles, and its effect on the elevation of the proximal femur in the DAA. METHODS: The study subjects comprised 5 freshly frozen cadavers with 10 normal hips. All of the anatomic dissections of all of the hips were performed through the DAA. The ischiofemoral ligament, piriformis, conjoint tendon, and external obturator were successively resected. All of the proximal femurs of the specimens were levered by a point tip curved retractor that was connected with a dynamometer. Through preliminary measurements, an applied force of 80 N was adopted and maintained on the curved retractor. The experiment was repeated to measure the displacement of the proximal femur being raised after the posterior structures of the hip joint had been resected in a stepwise fashion. The displacement of the retractor was recorded, and the data were then analyzed. RESULTS: The distance significantly increased after the ischiofemoral ligament was severed (P < 0.001). A prominent increase was demonstrated after the conjoint tendons were severed (P < 0.001). The distance insignificantly increased after the piriformis was severed (P > 0.05). After the obturator externus was cut off, the distance increased by an insignificant amount (P > 0.05). CONCLUSION: In DAA, the ischiofemoral ligament contributed stability when the femur was being raised. The main contribution of restriction was provided by the conjoint tendon. The tendons of the obturator externus muscle and piriformis muscle did not provide any significant restriction when the femur was being raised.

A new technique for arthroscopic reduction and fixation of displaced tibial intercondylar eminence fractures, using suture anchor and EndoButton system.

AIM: The study aims to describe a less invasive technique for displaced tibial intercondylar eminence fractures, using only one bone tunnel with suture anchor and EndoButton system. METHODS: Seventeen patients were followed up after arthroscopic fixation for tibial eminence fractures using suture anchor and EndoButton. The patients were followed with clinical examinations such as Lysholm, Tegner, and International Knee Documentation Committee (IKDC) rating scales. Radiographic assessments were also performed during the follow-up for evaluating the healing of the fracture. RESULTS: There were 14 male patients and 3 female patients with 10 right knees, and 7 left knees included. All the fractures healed anatomically at final follow-up. Also, no clinical signs of anterior cruciate ligament deficiency were detected. The mean Lysholm score improved significantly from 74.72 ± 3.24 (range from 70 to 79) to 96.2 ± 2.54 (range from 89 to 98) ( p < 0.001). The IKDC category was abnormal or severely abnormal preoperatively and all the patients improved to normal or nearly normal at final follow-up. The Tegner score also improved significantly postoperatively from 3.45 ± 1.02 to 6.34 ± 1.22 ( p < 0.001). CONCLUSION: The study demonstrated that the procedure is safe and effective, which can be another option for tibial intercondylar eminence fractures.

IRAK1 rs3027898 C/A polymorphism is associated with risk of rheumatoid arthritis.

IRAK1 and miR-499 play an important role in the etiology of rheumatoid arthritis. Few studies to date have focused on the influence of the IRAK1 rs3027898 C/A and hsa-mir-499 rs3746444 T/C polymorphisms in the susceptibility of the Chinese population to rheumatoid arthritis. We hypothesized that these polymorphisms may contribute to rheumatoid arthritis susceptibility. We studied IRAK1 rs3027898 C/A and hsa-mir-499 rs3746444 T/C gene polymorphisms in 214 rheumatoid arthritis cases and 478 controls in a Chinese population. Genotyping was performed by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the IRAK1 rs3027898 CC homozygote genotype was used as the reference group, the AA genotype was associated with significantly increased risk of rheumatoid arthritis (odds ratio (OR) = 1.91, 95 % confidence interval (CI) = 1.12-3.26, p = 0.017). A significantly increased risk of RA associated with the IRAK1 rs3027898 AA genotype was more evident among females, younger patients, CRP negative patients and both anti-CCP positive and negative patients compared with the IRAK1 rs3027898 CC/CA genotypes. The hsa-mir-499 rs3746444 T/C single nucleotide polymorphism (SNP) was not significantly associated with the risk for rheumatoid arthritis. Our findings suggest that the functional SNP IRAK1 rs3027898 C/A variant allele is associated with the development of rheumatoid arthritis. However, the hsa-mir-499 rs3746444 T/C polymorphism may not be associated with susceptibility to rheumatoid arthritis.

[Study on the preparation and application of individual artificial bone with carbon/carbon composites].

The present paper is aimed to study the preparation and application of individual artificial bone of carbon/carbon composites. Using computer tomography images (CT), we acquired a three-dimensional image. Firstly, we described bone contour line outlined with manual and automatic method by the binary volume data. Secondly, we created 3D object surface information by marching cubes. Finally, we converted this information to non-uniform rational B-spine (NURBS) by using geomagic software. Individual artificial bone with carbon/carbon composite was prepared through the CNC Machining Center. We replaced the humeral head of the tested rabbit, and then observed the effects of implantation in neuroimaging and pathological section. Using this method, we found that the bone shape processed and bone shape replaced was consistent. After implantation, the implant and the surrounding bone tissue bound closely, and bone tissue grew well on the surface of the implant. It has laid a sound foundation of the preparation using this method for individual artificial bone of carbon/carbon composite material.

Influence of BLK polymorphisms on the risk of rheumatoid arthritis.

B cell lymphocyte kinase (BLK) encodes a member of the Src kinase family and thus may influence the proliferation and differentiation of cells. A single nucleotide polymorphism (SNP) located in the first intron of BLK has shown that the risk C allele of rs2248932 is associated with lower levels of messenger RNA expression of BLK. We hypothesized that this polymorphism may contribute to rheumatoid arthritis (RA) susceptibility. We studied BLK rs2248932 T/C gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). When the BLK rs2248932 TT homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk of RA. In the recessive model, when the BLK rs2248932 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased susceptibility to RA. In stratification analyses, a significantly increased risk for RA associated with the BLK rs2248932 CC genotype was evident among younger patients, CRP-negative patients and anti-CCP-positive patients compared with the BLK rs2248932 TT/TC genotype. The risk was also significantly evident among RF-positive patients, patients with lower ESR levels, patients with lower or higher DAS28 score and patients with a lower functional class. These findings suggested that the functional SNP BLK rs2248932 T/C variant allele was associated with RA development. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. Validation in a larger study from a more diverse ethnic population is needed to confirm these findings.

Influence of MIF, CD40, and CD226 polymorphisms on risk of rheumatoid arthritis.

Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory mediator. It plays an important role part in the pathogenesis of several inflammatory and immune diseases. A functional single nucleotide polymorphism (SNP) of MIF -173 G/C is known to influence MIF promoter activity in T lymphoblast cell lines and is associated with a higher serum MIF level. The CD40 is also crucial for some relevant functions of the immune system and may be related to rheumatoid arthritis (RA). And CD226 is an important cell-surface receptor molecule involved in the adhesion and activation of T-cell. We hypothesized that these polymorphisms may contribute to RA susceptibility. We studied MIF -173 G/C, CD40, and CD226 gene polymorphisms in 214 patients with RA and 478 controls in a Chinese population. Genotyping was done by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the MIF -173 GG homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk for RA. In the recessive model, when the MIF -173 GG/GC genotypes were used as the reference group, the CC homozygote genotype was associated with a significant 1.56-fold increased susceptibility to RA. None of the CD40 rs1883832 C/T and CD226 rs763361 C/T polymorphisms achieved a significant difference in genotype distributions between cases and controls. In the stratification analyzes, a significantly increased risk for RA associated with the MIF -173 CC genotype was evident among CRP-negative patients compared with the MIF -173 GG/GC genotype. For the CD40 rs1883832 C/T variant, the risk effects of CD40 rs1883832 TT versus CD40 rs1883832 CC/CT were significant in men. These findings suggested that the functional SNP MIF -173 G/C variant allele was associated with the development of RA. However, CD40 and CD226 gene polymorphisms may not be associated with RA susceptibility. Due to the limitation of sample size, this study should be considered preliminary.