Comparison between infrapatellar and suprapatellar approaches for intramedullary nailing for the fractures of the tibial shaft.

INTRODUCTION: This study aimed to compare the outcomes at the clinical and functional levels of suprapatellar (SP) and infrapatellar (IP) approaches for intramedullary nailing in treating tibial shaft fracture. METHODS: Patients who underwent tibial shaft fracture intramedullary nailing by the SP approach or IP approach in a trauma center were retrospectively reviewed. The demographics, intraoperative fluoroscopy time, operation time, blood loss, irrigation volume, postoperative X-ray alignment, and complications of patients were compared between the two groups under different approaches. Lysholm knee score, visual analog score (VAS), and incidence of anterior knee pain (AKP) were assessed 1 year after surgery. RESULTS: The study finally included well-documented 81 patients (38 SP versus 43 IP). The SP group exhibited significantly shorter intraoperative fluoroscopy time than that of the IP group (81.7 ± 14.5 s vs. 122.0 ± 24.3 s, P < 0.001). Both aspects recorded a precise reduction of the fracture: angulation (2.1 ± 1.2° vs 3.1 ± 1.5°, P < 0.05) and translation (0.6 ± 0.8 mm vs 1.4 ± 1.5 mm, P < 0.05) in the coronal plane in the SP group. However, the sagittal plane recorded no such change (P > 0.05). The Lysholm knee score was higher in the SP group than that of the IP group (87 ± 8 vs. 80 ± 15, P < 0.05). The SP group displayed an evidently lower average VAS score than that of the IP approach group (0.3 ± 0.8 vs 1.3 ± 1.4, P < 0.001). Six cases (16%) in the SP group and 16 cases (37%) in the IP group experienced AKP 1-year post-operation (P < 0.05). As far as complications are concerned, neither group showed any significant difference (P > 0.05). CONCLUSION: Compared with the IP approach, the application of intramedullary nailing through the SP approach in treating tibial shaft fractures can effectively shorten the intraoperative fluoroscopy time, correct coronal plane angulation and translation deformity, reduce the incidence of AKP and improve postoperative function.

Capsular Healing in Interportal and Periportal Capsulotomy Methods of Hip Arthroscopy.

OBJECTIVE: To evaluate the midterm outcomes and the capsular healing in patients who had interportal capsulotomy versus periportal capsulotomy of hip arthroscopy. METHODS: Retrospectively reviewed 33 patients with labral tear received hip arthroscopy, with an average age of 41 (27-67) years, including 13 cases of Cam deformity and three cases of Pincer deformity. All patients had positive sign of flexion adduction internal rotation or flexion abduction external rotation. With MRI and radiographic (CT, X plain) imageological examination. MRI showed that all patients had labral tear. Radiographic finding (CT, X plain) showed the pathological changes of acetabular and femoral neck osteophyte. One group with 23 patients were treated with periportal capsulotomy. Another group with 10 patients were treated with interportal capsulotomy. All patients did not close the capsule. Clinical outcomes were measured with the Hip Outcome Score Activities of Daily Living (HOS-ADL) and the modified Harris Hip Score (mHHS), patient satisfaction measured with visual analogue scale (VAS). The healing of the capsule was evaluated by MRI. MRI showed continuous capsular indicated healing, discontinuous capsular indicated unhealing. Postoperatively 6 months, mHHS and HOS-ADL were obtained. Randomized controlled trials were used in this study for analysis. RESULTS: All patients were followed up with average time of 9.3 months(3-29 months). The postoperative symptoms were obviously relieved, the VAS decreased from (4.9 ± 0.6) to (1.2 ± 0.2) after 3 months postoperative. Follow up 6 months post-operation, patients in the interportal group, the mHHS and HOS-ADL scores improvement were respectively 69.4 ± 9.3 & 70 ± 8.8 pre-operation, and 92.5 ± 5.0 & 86.6 ± 5.4 post-operation (P < 0.05); Patients in the periportal group, the mHHS and HOS-ADL scores improvement were respectively 69.9 ± 15.8, 68.1 ± 15.0 pre-operation, and 90.1 ± 9.3 & 86.7 ± 7.9 post-operation (P < 0.05).The differences were statistically significant. Six months after operation, MRI showed that 23 patients with periportal capsulotomy, the capsule have healed, without other complications. Three of the ten patients with interportal capsulotomy were healed and seven were not. CONCLUSION: Interportal and periportal capsulotomy had good outcomes. The technique of periportal capsulotomy had little damage to the joint capsule. Although the capsule did not close, the capsule healed well in postoperative follow-up. The nonunion rate of the joint capsule was high in the interportal capsulotomy without close the capsule.

[Pressure side and tension side comminution of femoral neck cortex are independent risk factors for aseptic necrosis after femoral neck fracture surgery].

OBJECTIVE: To investigate the related factors of aseptic necrosis of femoral head after closed reduction and internal fixation of femoral neck fracture. METHODS: From January 2009 to January 2016, 236 patients with femoral neck fracture were treated with closed reduction and internal fixation with 3 hollow lag screws, including 111 males and 125 females, aged from 19 to 89 (50.17±12.88) years. According to the follow-up results, the correlation of aseptic necrosis of femoral head was analyzed. Univariate analysis of age, gender, injured side, body weight, injury mechanism, preoperative waiting time, Garden classification and whether there was comminution of femoral neck cortex was conducted to obtain the independent variables with significant difference. Then binary logistic regression analysis was conducted to explore the independent risk factors of avascular necrosis of femoral head. RESULTS: The average follow-up period of 236 cases was 4.58 years. There were significant differences in the range of injury (24.69% vs. 5.16%, χ2=19.405, P=0.000), operation waiting time>48 hours (20.00% vs. 6.38%, χ2=10.065, P=0.002), Garden type Ⅲ/Ⅳ (18.52% vs. 2.97%, χ2=13.357, P=0.000), femoral neck cortex comminution (66.67% vs. 4.88%, χ2=39.968, P=0.000). Multivariate logistic regression analysis showed that:injury mechanism [high energy injury, Exp (B)=4.397, 95%CI=(1.672-11.562), P=0.003], preoperative waiting time >48 h [Exp (B)= 3.060, 95%CI=(1.176-7.966), P=0.022], comminution of femoral neck cortex [comminution of femoral neck pressure side cortex, Exp (B)=3.944, 95%CI=(1.245-12.494), P=0.020;comminution of femoral neck pressure side and tension side cortex, Exp(B)= 23.761, 95%CI=(3.805-148.374), P=0.001) were independent risk factors for avascular necrosis after internal fixation of femoral neck fracture. Garden type Ⅲ/Ⅳ was not an independent risk factor in this study [Exp (B) = 1.985, 95%CI=(0.436-9.032), P=0.375]. CONCLUSION: High energy injury, preoperative waiting time (>48 h) and comminution of femoral neck cortex were independent risk factors for aseptic necrosis of femoral head. In addition, cortical comminution on the pressure side and tension side of the femoral neck is a strong prognostic risk factor for aseptic necrosis of the femoral head, because it indicates a more serious and complex injury mechanism.

LncRNA MEG3 Inhibits the Degradation of the Extracellular Matrix of Chondrocytes in Osteoarthritis via Targeting miR-93/TGFBR2 Axis.

BACKGROUND: As a degenerative joint disease, osteoarthritis (OA) is characterized by articular cartilage degradation. Long noncoding RNAs (lncRNAs) act critical roles in the regulation of OA development, including affecting the proliferation, apoptosis, extracellular matrix (ECM) degradation, and inflammatory response of chondrocytes. The current study's aim was to investigate the regulatory function and the underlying molecular mechanism of lncRNA MEG3 in ECM degradation of chondrocytes in OA. METHODS: In the current study, chondrocytes were induced by interleukin-1ß (IL-1ß) to simulate OA condition, and further assessed cell viability, lncRNA MEG3 and miR-93 expression levels. Overexpression or knockdown of lncRNA MEG3 in chondrocytes treated with IL-1ß were performed to investigate the function of MEG3 in regulating cell proliferation, apoptosis and ECM degradation using EdU assay, flow cytometry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot. The interaction between MEG3 and miR-93 was assessed using qRT-PCR. Furthermore, overexpression of miR-93 was performed as recovery experiment to explore the functional mechanism of MEG3. RESULTS: MEG3 was significantly downregulated in chondrocytes treated with IL-1ß, whereas miR-93 was upregulated concomitantly. Overexpression of MEG3 induced the proliferation, suppressed the apoptosis, and relieved the degradation of ECM in IL-1ß-induced chondrocytes. By contrast, knockdown of MEG3 suppressed the proliferation, promoted the apoptosis, and aggravated ECM degradation in IL-1ß induced chondrocytes. In addition, MEG3 was found to relieve the inhibitive expression of TGFBR2 as a competitive endogenous RNA (ceRNA) of miR-93, and then activated transforming growth factor-ß (TGF-ß) signaling pathway, regulated chondrocytes ECM degradation in IL-1ß induced chondrocytes subsequently. CONCLUSION: LncRNA MEG3 targeted miR-93/TGFBR2 axis, regulated the proliferation, apoptosis and ECM degradation of chondrocytes in OA.

Early complications of preoperative external traction fixation in the staged treatment of tibial fractures: A series of 402 cases.

BACKGROUND: Different external skeletal fixators have been widely used in preoperative traction of high-energy tibial fractures prior to a definitive surgical treatment. However, the early complications associated with this staged treatment for traction and soft tissue injury recovery have rarely been discussed. AIM: To analyze the early complications associated with preoperative external traction fixation in the staged treatment of tibial fractures. METHODS: A total of 402 patients with high-energy tibial fractures treated using preoperative external traction fixation at a Level 1 trauma center from 2014 to 2018 were enrolled in this retrospective study. Data regarding the demographic information, Tscherne soft tissue injury, fracture site, entry point placement, and duration of traction were recorded. Procedure-related complications such as movement and sensation disorder, vessel injury, discharge, infection, loosening, and iatrogenic fractures were analyzed. RESULTS: The mean patient age was 42.5 (18-71) years, and the mean duration of traction was 7.5 (0-26) d. In total, 19 (4.7%) patients presented with procedure-related complications, including technique-associated complications in 6 patients and nursing-associated complications in 13. Differences in the incidence of complications with respect to sex, affected side, soft tissue injury classification, and fracture sites were not observed. However, the number of complications due to hammer insertion was significantly reduced than those due to drill insertions (2.9% vs 7.4%). CONCLUSION: We found a low incidence of early complications related to the fixation. Furthermore, the complications were not significantly associated with the severity of the soft tissue injury and fracture site. Although relatively rough and more likely to cause pain, the number of complications associated with hammer insertion was significantly smaller than that of complications associated with drill insertion.

MicroRNA-675-3p regulates IL-1ß-stimulated human chondrocyte apoptosis and cartilage degradation by targeting GNG5.

Growing evidence has indicated that microRNAs (miRNAs) are modulators of osteoarthritis (OA) development and progression. In this study, we first evaluated the anti-apoptosis and chondroprotective effects of microRNA-675-3p (miR-675-3p) on interleukin-1ß (IL-1ß)-stimulated human chondrocytes. The overexpression of miR-675-3p inhibited apoptosis and cartilage matrix degradation and promoted cell proliferation in human chondrocytes. Target gene prediction and luciferase reporter assays suggested that G-protein subunit γ 5 (GNG5) may be the target gene of miR-675-3p. The overexpression of miR-675-3p inhibited IL-1ß-stimulated chondrocyte apoptosis, and this effect was reversed by the overexpression of GNG5. Finally, we used bioinformatic tools and biological methods to show that the long noncoding RNA X-inactive specific transcript (lncRNA XIST) could bind to miR-675-3p, which affects the expression of GNG5 mRNA. Our findings may substantiate miR-675-3p as a new treatment for OA.

A comparison of the use of a suprapatellar Chinese Aircraft-shaped Sleeve System versus suprapatellar intramedullary nailing for tibial shaft fractures: Outcomes over a one-year follow-up.

INTRODUCTION: This study aimed to investigate the effectiveness and safety of the Chinese Aircraft-shaped Sleeve (CASS) system on the clinical outcomes of tibial intermedullary nailing using a suprapatellar approach for the treatment of tibial fractures in a cohort of adult Chinese patients over a minimum one-year follow-up. METHODS: After institutional review board approval, skeletally mature patients with Orthopaedic Trauma Association (OTA) type 42 tibial shaft fractures were randomized into either a SP approach using CASS group or a conventional SP approach group after informed consent was obtained. The operations were performed by a single senior orthopaedic surgeon according to group assignments. A group of 33 patients were treated using the CASS system and the other group of 34 patients were treated using a conventional SP approach. Both groups fully complied with research requirements and completed 12 months of follow-up. Magnetic resonance images (MRI) were obtained for the evaluation of the patellofemoral joint (PFJ) and residual debris preoperatively, as well as one week and 12 months postoperatively. Radiographs were used to assess alignment and union, visual analog scores (VAS) were used to assess anterior knee pain, and range of motion (ROM) and the Lysholm knee scoring scales were used for evaluating the operated knee at the 12-month follow-up. RESULTS: Differences in cartilage lesion changes observed by MRI between the two groups were statistically significant (P = 0.030 at 1 week postoperatively; P = 0.025 at 12 months postoperatively). No significant differences were evident with respect to debris residue, malalignments, nonunion, VAS, ROM and Lysholm knee scoring scale with the exception of stair climbing (P = 0.02). CONCLUSION: Based on the data of this one-year clinical follow-up study, the SP approach using the CASS system offers the potential to benefit patients suffering from tibial shaft fractures, who will be treated with intramedullary nailing especially for smaller patients.

Anatomical Risk Factors of Anterior Cruciate Ligament Injury.

BACKGROUND: Nowadays, the anterior cruciate ligament (ACL) injury has been one of the most common diseases of the knee joint. The relationships between the ACL injury and the anatomical structures are still controversial. This study aimed to identify the anatomical risk factors of ACL injury by magnetic resonance imaging (MRI) of the knee. METHODS: This was a retrospective study of 125 patients undergoing primary ACL reconstruction between July 2013 and May 2017. Another 125 patients without any organic knee joint injury were served as controls. The shape of intercondylar notch, the intercondylar notch width index, the intercondylar notch height index, the α angle, the ß angle, and the medial and lateral tibial plateau slope were measured with MRI and compared. The data were compared by binary logistic regression to find the risk factors. RESULTS: The two groups differed in the proportion of male patients (70.4% vs. 52.0%, χ2 = 8.911, P = 0.003), but gender was excluded as a risk factor for ACL injury with regression analysis (odds ratio = 1.476, 95% confidence interval [CI]: 0.689-3.160, P = 0.317). The injured group was found to have a smaller notch width index (95% CI = 7.960E-23-2.154E-9, P < 0.001), a larger ß angle (95% CI = 1.311-1.785, P < 0.001), and a larger lateral tibial plateau slope (95% CI = 1.201-1.683, P < 0.001). The cutoff values of notch width index, ß angle, and the lateral tibial plateau slope were 0.252, 38.5°, and 7.5°, respectively. CONCLUSIONS: In this study, a narrow intercondylar notch (intercondylar notch width index <0.252), a larger lateral tibial slope (>7.5°), and larger ß angle (>38.5°) might be the factors associated with ACL injury. TRIAL REGISTRATION: ChiCTR-RRC-17014116; http://www.chictr.org.cn/showproj.aspx?proj=24119.

Application of the Chinese Aircraft-shaped Sleeve system in the treatment of tibial shaft fractures using a suprapatellar approach for tibial intramedullary nailing: a randomised controlled trial.

BACKGROUND: The use of the suprapatellar approach for intramedullary nailing has recently become popular for the treatment of tibial fractures. This study aimed to investigate the effectiveness of using the Chinese Aircraft-shaped Sleeve (CASS) system on the clinical outcomes of tibial intermedullary nailing using a suprapatellar approach for the treatment of tibial fractures in a cohort of adult Chinese patients. METHODS: Magnetic resonance images (MRI) of the knee joints of 212 healthy adults with normal lower limb function from May 2011 to May 2015 were obtained from a level I Chinese regional trauma centre. Sixty inpatients at the same trauma centre who underwent treatment for tibial shaft fractures from June 2015 to June 2018 were enrolled. Tibial intramedullary nailing fixation of tibial shaft fractures via the suprapatellar approach was performed with either a CASS system or a conventional sleeve. The measurements of patellofemoral joint anatomy, the surgical time, the assessments of the patellofemoral joint cartilage conditions, and information of residual debris based on arthroscopic analysis were subsequently collected. RESULTS: The mean patellar angle (PA), sulcus angle (SA), sulcus width (SW) and sulcus depth (SD) were 135.40 ± 6.20°, 142.37 ± 5.33°, 33.37 ± 2.73 mm, and 4.29 ± 0.63 mm, respectively. The surgical time until entry reaming commencement and the irrigation time were significantly lower in the CASS group (P < 0.001). The difference in cartilage damage rate between groups was statistically significant (P = 0.031); the difference in residual debris conditions was not statistically significant (P = 0.1967). CONCLUSION: The use of the CASS system could improve clinical outcomes of intramedullary nailing via suprapatellar approach for patients with a small patellofemoral joint space.

[Clinical study of the application of enhanced recovery after surgery in cervical spondylotic myelopathy].

OBJECTIVE: To evaluate the role of enhanced recovery after surgery in treating cervical spondylotic myelopathy. METHODS: The clinical data of 55 patients with cervical spondylotic myelopathy underwent surgical treatment from January 2012 to December 2015 were retrospectively analyzed. There were 30 males and 25 females, age from 36 to 71 years old with an average of (45.2±3.2) years, course of disease was for 1 to 12 months with an average of (4.5±1.8) months. The concept of enhanced recovery after surgery and perioperative management were applied to surgical treatment in 35 patients (study group), and the same period, 20 patients without strategy of enhanced recovery after surgery (control group). Thirty-eight patients were treated by anterior cervical discectomy decompression and fixation(ACDF), 17 patients were treated by posterior single-open door laminoplasty decompression. The activity time out of bed, hospitalization days after surgery were compared between two groups. Japanese Orthopaedic Association (JOA) score and visual analogue score(VAS) before operation, after operation at 1, 7, 30 days and 6, 12 months was respectively used to evaluate the neurological function and pain. RESULTS: All the patients were followed up for 12 to 18 months with an average of (14.3±1.5) months. There was no significant difference in age, gender, surgical methods, preoperative VAS, JOA score between two groups (P>0.05). The activity time out of bed was 3 to 8 h with an average of (5.54±1.54) h, postoperative hospitalization time was 3 to12 d with an average of (5.62±1.59) d in study group, while in control group, the activity time out of bed was 24 to 48 h with an average of (18.80±4.78) h, and postoperative hospitalization time was 7 to 17 d with an average of (9.85±1.94) d; there was significant difference between two groups (P<0.01). There was significant difference in VAS and JOA scores between two groups at 1, 7, 30 d after operation (P<0.01), and there was no significant difference at 6, 12 months after operation(P>0.05). There were no neurologic function deterioration, hematoma, wound infection, internal fixation loosening and other complications in study group during hospitalization and following-up;there were 2 cases of superficial wound infection in the control group, who healed by dressing change for 2 weeks;there was no significant difference between two groups(P>0.05). CONCLUSIONS: The strategy of enhanced recovery after surgery in treating cervical spondylotic myelopathy can promote the early recovery, shorten the length of stay and improve the patient's degree of satisfaction.

Association between expression of nuclear receptor co-activator 5 protein and prognosis in postoperative patients with osteosarcoma.

The aim of the present study was to investigate the association between the expression of nuclear receptor co-activator 5 protein (NCOA5) and the prognosis of postoperative patients with osteosarcoma. Human osteosarcoma samples were collected from 145 patients and normal bone tissues were collected from 100 individuals as controls. Immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) were employed to measure the levels of NCOA5 protein in cases of human osteosarcoma. The results from the RT-PCR analysis demonstrated that the positive rate of NCOA5 mRNA expression in human osteosarcoma was 17.24% (25/145). The positive rate in normal bone tissues was 84.00% (84/100), which was significantly higher compared with that of human osteosarcoma tissues (χ2=33.166; P<0.001). IHC staining indicated that the positive rate of NCOA5 protein in the osteosarcoma samples was 26.21% (38/145). The positive rate in normal bone tissues was 82.00% (82/100), which was significantly increased compared with that of human osteosarcoma tissues (χ2=28.166; P<0.001). NCOA5 mRNA and protein expression levels were consistent in human osteosarcoma tissues, and were lower than in control tissues. The expression of NCOA5 was low in human osteosarcoma tissues, while it was high in normal bone tissues. These low NCOA5 expression levels were associated with postoperative survival of human osteosarcoma.

Effects of low-dose X-ray irradiation on activated macrophages and their possible signal pathways.

Low-dose irradiation (LDI) has been used in clinics to treat human diseases, including chronic inflammation. This study assessed the effects of LDI on the inflammatory response of activated mouse primary peritoneal macrophages, and the underlying signal pathways. Primary peritoneal macrophages were isolated from mice and then incubated with lipopolysaccharide (LPS)-coated Ti microparticles (Ti-positive control) with or without brief exposure to LDI (X-ray, 0.5 Gy) 1 h later (Ti-LDI group) or left untreated in culture medium (Ti-negative control). The macrophages were then subjected to qRT-PCR, Western blot, cell viability CCK-8 assay, and ELISA. qRT-PCR analysis revealed the Ti-LDI group expressed significantly lower levels of IL-1ß, IL-6, and TNF-α mRNA than those of the Ti-positive control group, while the ELISA data showed that Ti-LDI group had significantly lower secretion of IL-1ß, IL-6, and TNF-α proteins. The most significant reduction associated with LDI was the secretion TNF-α protein, which barely increased from 13 to 25 h after treatment. Western blot data demonstrated that phosphorylation of p65 and ERK was much lower in the Ti-LDI group than in the controls. The data from the current study suggests that LDI of activated mouse macrophages was associated with significantly lower inflammation responses, compared with non-exposed activated macrophages, which was possibly through inhibition of the NF-κB and ERK pathways.

Expression of the NRF2 Target Gene NQO1 Is Enhanced in Mononuclear Cells in Human Chronic Kidney Disease.

Reduced nuclear factor erythroid 2-related factor 2 (NRF2) pathway activity was reported in models of chronic kidney disease (CKD). Pharmacological activation of NRF2 is supposed to improve renal function, but data concerning the NRF2 activity in human CKD are lacking. We investigated the NRF2 target NAD(P)H:quinone oxidoreductase 1 (NQO1) as a readout parameter for NRF2 activity in monocytes of CKD patients (n = 63) compared to those of healthy controls (n = 16). The NQO1 gene expression was quantified using real-time PCR and the protein content by in-cell Western assays. We found a 3-4-fold increase in NQO1 gene expression in CKD 1-5 (n = 29; 3.5 for NQO1/ribosomal protein L41; p < 0.001). This was accompanied by a 1.1-fold increase in NQO1 protein (p = 0.06). Cardiovascular disease prevalence was higher in CKD 1-5 patients with higher compared to those with lower NQO1 gene expression (p = 0.02). In advanced uremia, in dialysis patients (n = 34), NQO1 gene expression was less robustly upregulated than that in CKD 1-5, while NQO1 protein was not upregulated. We conclude that in mononuclear cells of CKD patients, the NRF2 pathway is activated by coexisting pathogenic mechanisms, but in advanced uremia, the effectiveness of this upregulation is reduced. Both processes could interfere with pharmacological NRF2 activation.

Ellipticine inhibits the proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via the STAT3 pathway.

OBJECTIVE: Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an alkaloid isolated from Apocyanaceae plants. This study was designed to investigate the effects of ellipticine on the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). METHODS: RA-FLSs were exposed to different concentrations of ellipticine (i.e., 0.5, 1, 2, 4 and 8 µM) for 24-72h and measured for viability, proliferation and apoptosis. The involvement of signal transducer and activators of transcription 3 (STAT3) signaling in the action of ellipticine was determined by Western blot analysis, luciferase reporter assay and rescue experiments. RESULTS: Ellipticine treatment significantly inhibited the viability and proliferation of RA-FLSs in a concentration-dependent manner. In contrast, ellipticine exposure did not alter the viability of normal human FLSs. Moreover, ellipticine triggered significant apoptosis and increased caspase-3 activity in RA-FLSs. Mechanistically, ellipticine reduced the phosphorylation of STAT3 and downregulated the expression of Mcl-1, cyclin D1 and Bcl-2. Luciferase reporter assay demonstrated that ellipticine treatment led to a significant inhibition of STAT3-mediated transcriptional activity in RA-FLSs. Overexpression of constitutively active STAT3 reversed the suppressive effects of ellipticine on RA-FLSs, which was accompanied by restoration of Mcl-1, cyclin D1 and Bcl-2. DISCUSSION AND CONCLUSIONS: Ellipticine shows anti-proliferative and pro-apoptotic effects on RA-FLSs through inhibition of the STAT3 pathway and may have therapeutic potential in RA.

Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response.

We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R) induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2-alpha (eIF2α) and activating transcription factor 4 (ATF4). We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 µM) treatment. We found that 100 µM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p)-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

Effect of low-dose X-ray irradiation and Ti particles on the osseointegration of prosthetic.

Low-dose irradiation (LDI) exhibits a positive effect on osteoblasts and inhibitory effect of inflammation. Here, we test the hypothesis that LDI can promote osseointegration and inhibit the inflammatory membrane formation in the presence of titanium (Ti) particles. Endotoxin-free titanium particles were injected into rabbit, prior to the insertion of a Ti6-Al-4-V sticks pre-coated with hydroxyapatite. Two days after operation, both distal femurs of the animal were exposed to 0.5 Gy X-ray irradiation. All ani-mals were euthanized 8 weeks after the operation. The PINP concentration was determined at day 0, 2, 4, and 8 weeks after operation. Trabecular morphology around the implants 8 weeks after operation was assessed using micro-CT, then the maximum push out force of simples was assessed using biomechanics test. Five samples in each group were chosen for bone histomorphology study without decalcification 8 weeks after operation. The results confirmed that the LDI can significantly improve ingrowth of bone into the prosthetic interface and stability of the prosthesis when there was no wear particles. Although promotion effects for bone formation induced by LDI can be counteracted by wear particles, LDI can significantly inhibit the interface membrane formation around the implant induced by wear particles. Based on these results, we conclude that LDI may be useful for enhancing the stability of prosthesis when there are no wear particles and for inhibiting the interface membrane formation during the early stage of aseptic loosening in the presence of wear particles. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1688-1696, 2016.