Inhibition of the PI3K/AKT pathway reduces tumor necrosis factor-alpha production in the cellular response to wear particles in vitro.

Joint replacement is the most effective treatment for end-stage osteoarticular disease. However, macrophage-mediated aseptic loosening of joint prosthesis severely hampers the clinical effects of joint replacement. Until now, the mechanism by which macrophages regulate the secretion of inflammatory cytokines after particle stimulation is not clear. It is well known that the PI3K/AKT pathway participates in multiple cellular processes, including cell growth, survival, and inflammation. However, whether the PI3K/AKT pathway participates in the proinflammatory response of macrophages after particle stimulation and secondary aseptic loosening is still unknown. In this study, ceramic and titanium particles of different sizes were prepared to stimulate macrophages. LY294002, a specific inhibitor of PI3K, was pretreated prior to particle stimulation. The expression of tumor necrosis factor-alpha (TNF-α) and all the subunits of PI3K and AKT were detected by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot. The result showed that LY294002 could suppress the RNA and protein expression of TNF-α in RAW264.7 cells after stimulation of different particles. The subunits of PI3K (p110ß and p85ß), followed by activation of phosphor-AKT (Ser473), participated in the regulation of activating macrophages by wear particles, ultimately resulting in the secretion of TNF-α.

[Case-control study on comprehensive rehabilitation for postoperative pain after spinal surgery].

OBJECTIVE: To evaluate the effect of interferential electrical stimulation (IES) in pain relief after spine surgery. METHODS: From January 2004 to December 2008, 166 patients after spine operation received pain treatment. All the patients were divided into two groups: the drug treatment group, which was the control group, including 46 cases, 22 patients were male and 24 patients were female, with an average age of (51.0 +/- 6.5) years; and the IES treatment group, including 120 cases, 50 patients were male and 70 patients were female, with an average age of (48.0 +/- 5.6) years. Before treatment, there were 4 patients with pain of Grade III in the control group, in which 3 patients had stenosis, 1 patient had spondylolisthesis; 42 patients had Grade II pain. In the IES group before treatment,17 patients had Grade II pain, in which 13 patients had stenosis, 4 patients had spondylolisthesis; 103 patients had Grade II pain. The preoperative and postoperative pains were evaluated and compared by the WHO Pain Criteria. RESULTS: The composing of IES group with pain grade III, II and I were 1/96/23, 0/17/103, 0/0/ 120 at the 3rd day, the 7th day and the 14th day after treatment respectively, while in the control group they were 4/42/0, 2/ 44/0, 0/4/42 respectively. There were statistical differences between the two groups with Kruskal-Wallis test. The percent of mid and severe grade pain decreased much faster in IES group. CONCLUSION: Interferential electrical stimulation (IES) therapy can improve patients' postoperative pain relief more quickly and reduce duration of hospitalization.

[Association of 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist gene with lumbar disc disease].

OBJECTIVE: To investigate the association of 86 bp variable number tandem repeat (VNTR) polymorphism of interleukin-1 receptor antagonist (IL-1Ra) gene with lumbar disc disease and intervertebral disc degeneration. METHODS: The 86 bp VNTR polymorphism of IL-1Ra gene was analyzed with PCR and electrophoresis for 81 patients with lumbar disc disease and 101 volunteers without sciatica (control). The grade of intervertebral disc degeneration was determined with magnetic resonance imaging, and the association of 86 bp VNTR polymorphisms with lumbar disc disease and intervertebral disc degeneration in those younger than 45 years was assessed. RESULTS: The presence of 86bp VNTR polymorphisms of IL-1Ra gene was detected in both patients with lumbar disc disease and the control subjects. The distribution of 86 bp VNTR polymorphisms of IL-1Ra gene showed no significant difference between the two groups, but the distributions of 1/1, 1/2 and 2/2 or 1, 2 genotypes differed significantly. The current data did not support a significant association between the distribution of IL-1Ra gene 86bp VNTR polymorphism and lumbar disc degeneration. CONCLUSIONS: IL-1Ra gene 86bp VNTR polymorphism is present among Chinese population in association with lumbar disc disease, but not with lumbar disc degeneration.

[The vitamin D receptor gene Tru I polymorphisms and its effect on the detection of Bsm I polymorphisms in Han nationality].

OBJECTIVE: To explore the polymorphisms of vitamin D receptor (VDR) gene Tru I polymorphisms and the influence of this variation on Bsm I polymorphisms in Han nationality. METHODS: Venous blood samples from 80 healthy individuals of Han nationality were collected and genomic DNA was extracted, VDR Bsm I and Tru I were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze the polymorphisms of VDR gene; After using another primers to test VDR Bsm I in the same samples, the consistence of each method was assessed. RESULTS: The frequencies of the VDR Tru I genotype in the groups were: TT 68.7%, Tt 26.3%, tt 5.0%; VDR Bsm I were: BB 6.2%, Bb 52.5%, bb 41.3%; Both polymorphisms were under Hardy-Weinberg equilibrium. After using another pair of primer, the frequencies of Bsm I genotype were BB 20.0%, Bb 26.2%, bb 53.8%, 22 genotype Bb changed to genotype BB or genotype bb in comparison with the result of first detection. CONCLUSION: The VDR Tru I polymorphism is found in the Han nationality, the distribution of this site's polymorphism is different from that of other nationalities. The presence of Tru I variation can result in some allele of Bsm I genotype drop-out in some study.

[The risk factors and preventive strategies of heterotopic ossification after artificial disc replacement in lumbar spine].

OBJECTIVE: To analyze the risk factors of heterotopic (HO) ossification after total lumbar disc replacement and probe the preventive strategies for it. METHODS: The radiographs and clinical data of 78 discs in 65 patients who received artificial lumbar disc replacement (ADR) from April 1998 to December 2003 were analyzed retrospectively by two radiologists and one orthopaedic surgeon and then postoperative HO were graded according to McAfee system. The bony formations in disc spaces, time of HO were found, and range of motion (ROM) of the operated levels were measured on radiographic films. In addition, the risk factors such as preoperative peri-annulus ossification, bony endplates injuries, and subsided or mal-position of the prostheses were also analyzed by Logistic regression analysis. RESULTS: Postoperative HO was found in 10 spaces of 9 cases. Class I of HO were occurred in 7 patients at means 2.1 years postoperatively with normal range of motion preserved. Three of them turned into class II or III with 10 degrees of mean ROM in the following 2.5 years. Another 2 (2/9) cases with preoperative peri-annulus ossification had bridging trabecular bone (class III) between the endplates and 9 degrees of ROM 2 years after surgery, then turned into class IV at 6 years with 0 degrees and 4 degrees of motion in the operated levels. As the risk factors of HO, preoperative annulus ossification (2 cases), bony endplates injuries (5 cases), mal-positioned prostheses (2 cases) and subsided prostheses (2 cases) were found simultaneity with significant positive relation to HO occurred (P < 0.05). CONCLUSIONS: Factors such as preoperative ossification of annulus, endplate injuries, prosthesis subsided and mal-position would have higher risks to have HO occurred after ADR, but ROM of most affected levels are preserved. Strict control indication and avoid all above risk factors can prevent HO occurring effectively.

[The role of artificial disc replacement in restoring lumbar segment motion and intervertebral height].

OBJECTIVE: To investigate the role of artificial disc replacement (ADR) in restoring lumbar segment motion and intervertebral height (IH). METHODS: Seventy-five patients with intervertebral disc diseases underwent artificial disc replacement and were divided into 3 groups to be followed up for 2 years (group A, n = 32), 3 years (group B, n = 27), and 5 years (group C, n = 19) respectively. Before the operation and during the follow-up the range of motion (ROM) of the involved lumbar segments and IH were assessed. RESULTS: The mean ROM and IH of the group A were 15 degrees and 14.1 mm respectively during the follow-up 2 years after operation. The mean ROM and IH of the group B were 14.2 degrees and 13.8 mm respectively during the follow-up 2 years after the operation and 13.7 degrees and 13.4 mm respectively during the follow-up 3 years after operation. The mean ROM and IH of the group C were 9.1 degrees and 11.5 mm respectively during the follow-up 2 years after the operation and 8.8 degrees and 11.0 mm respectively during the follow-up 3 years after operation, and 8.0 degrees and 10.3 mm respectively during the follow-up 5 years after operation. No significant differences in ROM and IH were found among different groups at any time point (all P > 0.05). Malposition was found in immediately after operation in 11 patients, all of the group C. During the follow-up, 3 cases of prostheses subsidence and 3 cases of annular ossification were found. No severe complications appeared. CONCLUSION: ADR is effective in restoring the ROM and IH of vertebrae suffering from intervertebral disc diseases.