Lipoxin A4-Mediated p38 MAPK Signaling Pathway Protects Mice Against Collagen-Induced Arthritis.

The aim of the article was to study the mechanism of Lipoxin A4 (LXA4)-mediated p38 MAPK pathway protecting mice against collagen-induced arthritis (CIA). The impact of LXA4 (0, 5, 10, 15 nM) on synoviocytes proliferation of CIA mice was detected using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. CIA mice were treated with LXA4, SB203580 (a p38 inhibitor), and/or anisomycin (a p38 agonist), and the arthritis severity score in each mouse was determined. The gene or protein expressions were detected with Western Blotting, ELISA, or qRT-PCR. LXA4 inhibited the synoviocytes proliferation of CIA mice with decreased levels of TNF-α, IL-6, IL-1ß, and IFN-γ and reduced p-p38/total p38 expression in synoviocytes in a dose-dependent manner. LXA4 levels were decreased in synovial tissues and plasma of CIA mice, but p-p38/total p38 expression was increased in synovial tissues. LXA4 could downregulate p-p38/total p38 expression in synovial tissues of CIA mice. Both LXA4 and SB203580 reduced arthritis severity score of CIA mice with the reduction of synovial tissue hyperplasia and inflammatory cell infiltration. CIA mice treated with LXA4 and SB203580 had lower levels of TNF-α, IL-6, IL-1ß, and IFN-γ, accompanying decreased MDA as well as increased SOD, CAT,and GPx. However, anisomycin could reverse the protect effects of LXA4 on CIA mice regarding the abovementioned inflammatory factors and oxidative stress indexes. LXA4 protected mice against collagen-induced arthritis via inhibiting p38 MAPK signaling pathway, which may be a potential new therapeutic target for rheumatoid arthritis.

Raloxifene improves TNF-α-induced osteogenic differentiation inhibition of bone marrow mesenchymal stem cells and alleviates osteoporosis.

Effect of raloxifene (RLF) on the improvement of inhibited osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) resulted from tumor necrosis factor-α (TNF-α) induction, thus alleviating the progression of osteoporosis (OP), was investigated. An in vivo OP rat model was constructed by performing the procedures of ovariectomy (OVX). Rats were randomly divided into sham group, OVX group and RLF+OVX group. BMSCs were extracted from healthy rats, and randomly divided into control group, TNF-α group, RLF group and TNF-α+RLF group. Viability and cellular calcification ability in each group were detected. The relative levels of osteocalcin (OCN), Runx2 and NF-κB in cells with different treatments were determined. The body weight of rats in the OVX group and RLF+OVX group gradually increased compared with that in the sham group on the 8th week. No significant difference in body weight was observed between the rats of the OVX group and RLF+OVX group. Bone metabolism index (BMD) in the rats of the RLF+OVX group was higher than that of the OVX group, and lower compared with that of the sham group. Compared with the sham group, the elastic/max radial degree and elastic/max load of femora were reduced in the OVX group and RLF+OVX group, especially in the OVX group. The relative levels of OCN and Runx2, as well as the ALP activity and calcification ability, were decreased in the OVX group compared with the sham group, and the effect was partially reversed by the RLF treatment. After osteogenic differentiation of BMSCs, the viability and calcification ability were markedly reduced in TNF-α group, which was reversed by RLF treatment. Moreover, TNF-α induction downregulated the relative levels of OCN and Runx2, and RLF treatment could enhance their levels. The upregulated NF-κB protein level, induced by TNF-α, was reduced after RLF treatment. TNF-α induction inhibits osteogenic differentiation of BMSCs, which could be remarkably alleviated by RLF. It is suggested that RLF contributes to the alleviation of OP progression.

Long noncoding RNA XIST regulates osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting miR-9-5p.

This study aimed to investigate whether X inactivate-specific transcript (XIST) regulated the expression of tissue non-specific alkaline phosphatase (ALPL) through miR-9-5p to promote osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). We elucidated the molecular regulation mechanisms of XIST underlying osteogenic differentiation of hBMSCs. In osteoporotic patients with hBMSCs, the expression of miR-9-5p was upregulated and the expression of XIST was downregulated. When hBMSCs were treated with osteogenic induction, the expression of XIST was increased and the expression of miR-9-5p was decreased. The osteogenic differentiation of hBMSCs was significantly decreased after knocking down XIST. Luciferase analysis revealed that XIST could directly bind to miR-9-5p and exert a negative regulatory effect on its expression. MiR-9-5p could bind directly to the 3'-UTR of ALPL and inhibit the expression of ALPL. Knockout of XIST reduced the expression of ALPL, while co-transfection of the miR-9-5p inhibitor could reverse the expression of the ALPL gene. In hBMSCs, overexpression of XIST upregulated the expression of ALPL, but the miR-9-5p mimic could reverse the expression of ALPL. Furthermore, silencing of ALPL could downregulate the expression of osteopontin(OPN) and osteocalcin(OCN) induced by miR-9-5p inhibitors. In conclusion, XIST regulated the expression of ALPL by targeting miR-9-5p. It could be used as a positive regulator of osteogenic differentiation of hBMSC.

Comparison of intravenous, topical or combined routes of tranexamic acid administration in patients undergoing total knee and hip arthroplasty: a meta-analysis of randomised controlled trials.

OBJECTIVE: This study aimed to compare the effects of intravenous, topical and combined routes of tranexamic acid (TXA) administration on blood loss and transfusion requirements in patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA). DESIGN: This was a meta-analysis of randomised controlled trials (RCT) wherein the weighted mean difference (WMD) and relative risk (RR) were used for data synthesis applied in the random effects model. Stratified analyses based on the surgery type, region, intravenous and topical TXA dose and transfusion protocol were also conducted. The main outcomes included intraoperative and total blood loss volume, transfusion rate, low postoperative haemoglobin (Hb) level and postoperative Hb decline. However, the secondary outcomes included length of hospital stay (LOS) and/or occurrence of venous thromboembolism (VTE). SETTING: We searched the PubMed, Embase and Cochrane CENTRAL databases for RCTs that compared different routes of TXA administration. PARTICIPANTS: Patients undergoing TKA or THA. INTERVENTIONS: Intravenous, topical or combined intravenous and topical TXA. RESULTS: Twenty-six RCTs were selected, and the intravenous route did not differ substantially from the topical route with respect to the total blood loss volume (WMD=30.92, p=0.31), drain blood loss (WMD=-34.53, p=0.50), postoperative Hb levels (WMD=-0.01, p=0.96), Hb decline (WMD=-0.39, p=0.08), LOS (WMD=0.15, p=0.38), transfusion rate (RR=1.08, p=0.75) and VTE occurrence (RR=1.89, p=0.15). Compared with the combined-delivery group, the single-route group had significantly increased total blood loss volume (WMD=198.07, p<0.05), greater Hb decline (WMD=0.56, p<0.05) and higher transfusion rates (RR=2.51, p<0.05). However, no significant difference was noted in the drain blood loss, postoperative Hb levels and VTE events between the two groups. The intravenous and topical routes had comparable efficacy and safety profiles. CONCLUSIONS: The combination of intravenous and topical TXA was relatively more effective in controlling bleeding without increased risk of VTE.

[Effect of Bryan cervical disc replacement on cervical curvature and replacement segment in treating cervical spondylosis].

OBJECTIVE: To investigate the effect of Bryan cervical disc replacement on cervical curvature and replacement segment in the treatment of cervical spondylosis, and analyze its clinical efficacy. METHODS: Forty-nine patients underwent Bryan artificial cervical disc replacement from August 2010 to August 2013 were retrospectively analyzed. There were 26 males and 23 females, aged from 27 to 66 years old with an average of 48.5 years. Including 21 cases of nerve root type, 16 cases of spinal cord type, 12 cases of mixed type. And 21 cases were single segment replacement, 28 cases were double segments replacement. Preoperative and postoperative pain was compared using visual analogue scale(VAS);cervical function was observed by Japanese Orthopedic Association Scores (JOA) and Neck Disability Index (NDI);cervical lordosis curvature, function spinal unit(FSU) curvature, activities of replacement and adjacent segment, FSU activity were measured by cervical X-rays. Clinical effects were evaluated by the Odom method. RESULTS: All the patients were followed up for 18.5 to 37.3 months with an average of 33.1 months. Pvoperative VAS, JOA, NDI scores were 7.08±1.55, 5.2±1.9, 39.96±7.06 before operation, 3.76±2.33, 13.20±1.20, 25.20±6.64 at 3 months after operation, and 2.80±1.50, 14.3±1.6, 24.24±7.89 at the last follow-up. Patients at three months and the last follow-up after operation were obviously improved in their VAS, JOA, and NDI scores (P<0.05). There was no significant difference between the scores at last follow-up and 3 months after operation. Cervical lordosis changed from (10.64±4.26)° preoperatively to (13.68±4.56) ° at the last follow-up;the FSU curvature from (5.40±0.41) °to (9.92±2.00) °at the last follow-up (P<0.05). The range of motion of the cervical spine preoperatively, 3 month postoperatively, and at the last follow-up were(70.84±6.17)°, (60.00±6.58)°, (71.48±4.61)°; FSU activities were(12.00±0.49)°, (9.36±0.26)°, (12.52±0.33)°;the activities of replacement segment were (10.48±0.67)°, (7.24±0.34)°, (9.28±0.36)°;the activities of upper segment of replacement were (10.52±0.60)°, (8.60±0.30)°, (10.44±0.43)°;the activities of lower segment of replacement were (8.48±0.40)°, (6.56±0.36)°, (9.60±0.39)°;there were significant differences in above items preoperatively and 3 months postoperatively(P<0.05); and there were no significant difference preoperatively and at the last follow-up(P>0.05). Pharyngeal discomfort and hoarseness occurred in 5 cases, and were recovered within 2 weeks after operation;heterotopic ossification occurred in 1 case at 6 months after operation;displacement of prosthesis occurred in 1 case at 12 months after operation. Based on Odom standard to evaluate the clinical outcome, 20 cases obtained excellent results, with 27 good, 2 general. CONCLUSIONS: Bryan artificial cervical disc replacement not only generate good clinical effects, but may also restore the cervical lordosis and FSU curvature, while retaining the activities of replacement segment, and restoring overall cervical biomechanical functions.

Cervical anterior hybrid technique with bi-level Bryan artificial disc replacement and adjacent segment fusion for cervical myelopathy over three consecutive segments.

This study aimed to assess the preliminary clinical efficacy and feasibility of the hybrid technique for multilevel cervical myelopathy. Considering the many shortcomings of traditional treatment methods for multilevel cervical degenerative myelopathy, hybrid surgery (bi-level Bryan artificial disc [Medtronic Sofamor Danek, Memphis, TN, USA] replacement and anterior cervical discectomy and fusion) should be considered. Between March 2006 and November 2012, 108 patients (68 men and 40 women, average age 45years) underwent hybrid surgery. Based on the Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), and Odom's criteria, the clinical symptoms and neurological function before and after surgery were evaluated. Mean surgery duration was 90minutes, with average blood loss of 30mL. Mean follow-up duration was 36months. At the final follow-up, the mean JOA (± standard deviation) scores were significantly higher compared with preoperative values (15.08±1.47 versus 9.18±1.22; P<0.01); meanwhile, NDI values were markedly decreased (12.32±1.03 versus 42.68±1.83; P<0.01). Using Odom's criteria, the clinical outcomes were rated as excellent (76 patients), good (22 patients), fair (six patients), and poor (four patients). These findings indicate that the hybrid method provides an effective treatment for cervical myelopathy over three consecutive segments, ensuring a good clinical outcome.

[Clinical study of a cervical anterior Hybrid technique with posterior longitudinal ligament retained for cervical spondylosis].

OBJECTIVE: To explore the clinical effects and significances of a cervical anterior Hybrid technique with posterior longitudinal ligament retained in treating cervical spondylosis. METHODS: The clinical data of 138 patients with cervical spondylosis underwent cervical anterior Hybrid surgery were retrospectively analyzed from March 2009 to March 2013. There were 52 males and 86 females,the age ranged from 36 to 58 years old with an average of 45.3 years. Course of disease was from 3 to 16 months. Cervical spondylosis classification included 22 cases with nerve root type, 68 cases with myelopathic type, 48 cases with mixed type. All patients were treated with the primary Hybrid surgery and their cervical posterior longitudinal ligaments were retained in anterior decompression. JOA score and image examination were used to evaluate clinical effect, and image examination included range of motion of the replacement segment, range of motion of the whole cervical spine, the sagittal diameter of the spinal cord before and after operation. RESULTS: All operations were successful and operation time was 60 to 125 min (averaged 90.6 min), perioperative bleeding was 10 to 60 ml (averaged 30.1 ml). All patients were followed up from 12 to 48 months with an average of 22.2 months. All pathological segments obtained fully decompression, reserved posterior longitudinal ligament had no obvious hypertrophy, proliferation and calcification. The prosthesis had good location and the incision healed well without complications. Upper limbs root symptoms were completely relieved in the patients with cervical spondylotic radiculopathy, muscle strengths and sensations got different recovery in the patients with cervical spondylotic myelopathy. JOA score was increased from preoperative 8.62±1.22 to final follow-up 14.26±1.47 (P<0.05). Artificial intervertebral discs were stabilized in the patients, the replacement segment and range of motion of whole cervical spine were respectively (14.2± 5.6)° and (33.8±10.3)°, there was no significant differences between preoperative and postoperative (P>0.05). Spinal cord sagittal diameter was increased from preoperative (5.2±1.3) mm to postoperative (8.8±0.5) mm (P<0.05). CONCLUSION: Anterior cervical Hybrid surgery with posterior longitudinal ligament retained can achieve fully decompression and good clinical efficacy, we recommend retaining the normal posterior longitudinal ligament in surgery as complete as possible.

Multivariate analysis of risk factors for predicting supplementary posterior instrumentation after anterolateral decompression and instrumentation in treating thoracolumbar burst fractures.

BACKGROUND: Although anterolateral decompression and instrumentation has several advantages in treating thoracolumbar burst fractures, the risk factors for supplementary posterior instrumentation are still unclear. METHODS: We retrospectively reviewed 238 patients who underwent anterolateral decompression and instrumentation for single-level thoracolumbar burst fractures from January 2010 and March 2012. The influences of several potential risk factors that might affect supplementary posterior instrumentation were assessed using univariate and multivariate analyses. RESULTS: Twenty seven patients who developed worsening back pain without neurological deterioration after the anterolateral approach treatment need further posterior instrumentation fixation. The univariate analysis showed that age, disruption of the posterior longitudinal ligament complex (PLC), and fracture level were the risk factors for supplementary posterior instrumentation. However, age and integrity of the PLC were the independent risk factors for supplementary posterior instrumentation by multivariate analyses. CONCLUSIONS: Supplemental posterior instrumentation was necessary in 11.3% of cases following anterolateral decompression and instrumentation in the present study. Older age and disruption of the PLC were the independent risk factors in prediction of supplementary posterior instrumentation in treating thoracolumbar burst fractures.

[Application of exercise therapy on rehabilitation after selective posterior rhizotomy (SPR) in children with cerebral palsy].

OBJECTIVE: To observe the clinical effect of exercise therapy on rehabilitation after selective posterior rhizotomy (SPR) in children with cerebral palsy, so as to provide reliable rehabilitation method for children with cerebral palsy. METHODS: Two hundred and twenty-six children with cerebral palsy were treated in the study during September 2003 to April 2007. All the patients were randomly divided into the training and control groups. There were 113 patients in the treatment group, including 66 males and 47 females, ranging in age from 3 to 8 years, with an average of (6.5 +/- 1.2) years, and the patients were treated with SPR as well as exercise therapy. Among 113 patients in the control group, 59 patients were male and 54 patients were female, ranging in age from 3 to 10 years, with an average of (6.9 +/- 1.5) years, and the patients were treated with SPR simply. Gross Motor Function Measure (GMFM), passive range of motion and muscle tension were used to evaluate therapeutic effects before and after treatment for both groups. RESULTS: All the patients were followed up for 6 to 18 months (averaged 8 months). There were significant improvements in training group compared with the control group on GMFM (134.29 +/- 46.43, P < 0.05), passive range of motion (dorsiflexion of the ankle 14.2 +/- 3.1 degree, P < 0.05) and muscle tension (1.27 +/- 0.42, P < 0.05). CONCLUSION: Physical therapy has more effective on rehabilitation after SPR for children with cerebral palsy, which can decrease spasticity and muscle tension and improve motor function.

[Treatment of equinovarus caused by cerebral palsy with neurotomy of muscular branch of tibial nerve].

OBJECTIVE: To evaluate clinical effect of neurotomy of muscular branch of tibial nerve for the treatment of equinovarus caused by cerebral palsy. METHODS: Fifty-two cases of equinovarus caused by cerebral palsy were treated with neurotomy of muscular branch of tibial nerve. The male was 33 (38 feet) and the female 19 (26 feet) with the average age of 7.8 years old (from 6 to 10). The muscular tension according to Ashworsh grade, 34 cases were grade III and 18 cases were grade IV. The ankle clonus was positive in 42 cases. RESULTS: All cases were followed up for 1-3 years with the average of 2.6 years. The spastic gait of cases had obviously improved and abnormity had no recurred. According to corrective degree of abnormity and satisfactive condition of patients, evaluation of the effect were excellent in 32 cases, good in 14, poor in 6. CONCLUSION: Neurotomy of muscular branch of tibial nerve is the safe and effective method for the treatment of equinovarus caused by cerebral palsy.