TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-κB/CXCL3 axis.

Objective: Osteoarthritis (OA) is the most prominent chronic arthritic disease, affecting over 3 billion people globally. Synovial macrophages, as immune cells, play an essential role in cartilage damage in OA. Therefore, regulating macrophages is crucial for controlling the pathological changes in OA. Triggering receptor expressed on myeloid cells 2 (TREM2), as expressed on immune cell surfaces, such as macrophages and dendritic cells, has suppressed inflammation and regulated M2 macrophage polarization but demonstrated an unknown role in synovial macrophage polarization in OA. This study aimed to investigate TREM2 expression downregulation in OA mice macrophages. Furthermore, the expression trend of TREM2 was associated with polarization-related molecule expression in macrophages of OA mice. Results: We used TREM2 knockout (TREM2-KO) mice to observe that TREM2 deficiency significantly exacerbated the joint inflammation response in OA mice, thereby accelerating disease progression. Separating macrophages and chondrocytes from TREM2-KO mice and co-cultivating them significantly increased chondrocyte apoptosis and inhibited chondrocyte proliferation. Further, TREM2 deficiency also significantly enhanced phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway activation, increasing nuclear factor kappa light chain enhancer of activated B cells (NF-κB) signaling and C-X-C Motif Chemokine Ligand 3 (CXCL3) expression. Furthermore, NF-κB signaling pathway inhibition significantly suppressed arthritis inflammation in OA mice, thereby effectively alleviating TREM2 deficiency-related adverse effects on chondrocytes. Notably, knocking down CXCL3 of TREM2-KO mice macrophages significantly inhibits inflammatory response and promotes chondrocyte proliferation. Intravenous recombinant TREM2 protein (soluble TREM2, sTREM2) injection markedly promotes macrophage polarization from M1 to M2 and improves the joint tissue pathology and inflammatory response of OA. Conclusion: Our study reveals that TREM2 promotes macrophage polarization from M1 to M2 during OA by NF-κB/CXCL3 axis regulation, thereby improving the pathological state of OA.

NAMPT-Improved Mitochondrial Function Alleviates Degenerative Rotator Cuff Tendinopathy in Aged Mice.

BACKGROUND: Age-related rotator cuff tendinopathy (RCT) is associated with increased rotator cuff tear and postoperative retear rates. This study aimed to determine whether nicotinamide phosphoribosyltransferase (NAMPT) can alleviate degenerative RCT and prevent postoperative retears by reversing mitochondrial dysfunction in aged mice. METHODS: We assigned 32 young (4 months) and 64 aged (19 to 20 months) male wild-type C57BL/6 mice to young, aged, and aged NAMPT-treated (ANAMPT) groups (n = 32 each). Mice in the ANAMPT group underwent subacromial injection with NAMPT-loaded fibrin gel, whereas the other 2 groups were injected with fibrin gel alone. Histological staining and each of the biomechanical and mitochondrial function tests were performed using 8 samples each. RESULTS: Histological staining in the aged group revealed decreased cellularity, disrupted fiber architecture, and reduced type-I collagen content inside tendon tissues proximal to the enthesis, demonstrating the spontaneous development of age-related degenerative RCT. Compared with the young group, the maximum tendon-to-bone failure load (4.22 ± 0.81 versus 5.52 ± 0.81 N, p = 0.0106) and maximum suture cut-through force (0.83 ± 0.08 versus 1.07 ± 0.10 N, p = 0.0006) of degenerated tendon tissues in the aged group were significantly lower. Significantly reduced nicotinamide adenine dinucleotide (NAD + ) levels, adenosine triphosphate (ATP) production, and citrate synthase activity indicated that mitochondrial dysfunction was closely related to the development of the degenerative RCT. Furthermore, NAMPT-improved mitochondrial function alleviated age-induced degenerative histological changes and increased the maximum failure load (5.32 ± 0.68 N, p = 0.0375) and maximum suture cut-through force (0.99 ± 0.13 N, p = 0.0285). CONCLUSIONS: Spontaneously developed degenerative RCT in aged mice mimicked the clinical situation in elderly patients. NAMPT-improved mitochondrial function could alleviate age-induced degenerative RCT and prevent postoperative suture cut-through of tendons with degenerative RCT. CLINICAL RELEVANCE: This study confirmed the spontaneous development of degenerative RCT in aged mice, which will facilitate future studies of this condition. The results also suggest that NAMPT offers a novel therapeutic approach for treating age-related degenerative RCT.

Nicotinamide Phosphoribosyltransferase-elevated NAD+ biosynthesis prevents muscle disuse atrophy by reversing mitochondrial dysfunction.

BACKGROUND: It is well known that muscle disuse atrophy is associated with mitochondrial dysfunction, which is implicated in reduced nicotinamide adenine dinucleotide (NAD+ ) levels. Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in NAD+ biosynthesis, may serve as a novel strategy to treat muscle disuse atrophy by reversing mitochondrial dysfunction. METHODS: To investigate the effects of NAMPT on the prevention of disuse atrophy of skeletal muscles predominantly composed of slow-twitch (type I) or fast-twitch (type II) fibres, rabbit models of rotator cuff tear-induced supraspinatus muscle atrophy and anterior cruciate ligament (ACL) transection-induced extensor digitorum longus (EDL) atrophy were established and then administered NAMPT therapy. Muscle mass, fibre cross-sectional area (CSA), fibre type, fatty infiltration, western blot, and mitochondrial function were assayed to analyse the effects and molecular mechanisms of NAMPT in preventing muscle disuse atrophy. RESULTS: Acute disuse of the supraspinatus muscle exhibited significant loss of mass (8.86 ± 0.25 to 5.10 ± 0.79 g; P < 0.001) and decreased fibre CSA (3939.6 ± 136.1 to 2773.4 ± 217.6 µm2 , P < 0.001), which were reversed by NAMPT (muscle mass 6.17 ± 0.54 g, P = 0.0033; fibre CSA, 3219.8 ± 289.4 µm2 , P = 0.0018). Disuse-induced impairment of mitochondrial function were significantly improved by NAMPT, including citrate synthase activity (40.8 ± 6.3 to 50.5 ± 5.6 nmol/min/mg, P = 0.0043), and NAD+ biosynthesis (279.9 ± 48.7 to 392.2 ± 43.2 pmol/mg, P = 0.0023). Western blot revealed that NAMPT increases NAD+ levels by activating NAMPT-dependent NAD+ salvage synthesis pathway. In supraspinatus muscle atrophy due to chronic disuse, a combination of NAMPT injection and repair surgery was more effective than repair in reversing muscle atrophy. Although the predominant composition of EDL muscle is fast-twitch (type II) fibre type that differ from supraspinatus muscle, its mitochondrial function and NAD+ levels are also susceptible to disuse. Similar to the supraspinatus muscle, NAMPT-elevated NAD+ biosynthesis was also efficient in preventing EDL disuse atrophy by reversing mitochondrial dysfunction. CONCLUSIONS: NAMPT-elevated NAD+ biosynthesis can prevent disuse atrophy of skeletal muscles that predominantly composed with either slow-twitch (type I) or fast-twitch (type II) fibres by reversing mitochondrial dysfunction.

Research on the Influence of the Allogeneic Bone Graft in Postoperative Recovery After MOWHTO: A Retrospective Study.

Purpose: To compare the effects of an allogeneic bone graft and a non-filled bone graft on the rate of osteotomy gap union in medial opening wedge high tibial osteotomy (MOWHTO) with an opening width less than 10 mm. Methods: A total of 65 patients undergoing MOWHTO between January 2018 and December 2020 were enrolled in this retrospective study. The patients were divided into two groups: the allograft group (MOWHTO with allogeneic bone grafting, 30 patients) and the non-filling group (MOWHTO without bone void fillers, 35 patients). The clinical outcomes, including the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC), Lysholm score, and post-operative complications, were compared. The radiographic evaluation included changes in hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), femorotibial angle (FTA), and weight-bearing line ratio (WBLR) at pre-operation, at two-day post-operation, and the last follow-up. Radiographs were obtained at three, six and twelve months post-surgery, and at the time of the last follow-up to assess the fill area of the osteotomy gap. The union rate of the osteotomy gap was calculated and compared, and risk factors that may affect the rate of osteotomy gap union were also discussed. Results: The rate of osteotomy gap union at 3 and 6 months after the operation in the allograft group was significantly higher compared with the non-filling group (all P<0.05), while no significant difference was found after the 1-year post-operative and at the last follow-up. Also, the WOMAC and Lysholm scores of the allograft group were significantly higher than those of the non-filling group (all P<0.05), and there was no significant difference between the two groups at the last follow-up. Conclusion: Filling the gaps with the allograft bones may accelerate the union of osteotomy gap, improve clinical outcomes, and have important implications for patient rehabilitation in the early post-operative course. Bone grafting did not affect the final rate of osteotomy gap union and the clinical score of patients.

Effect of Partial Fibula Osteotomy Combined with Arthroscopic Debridement Surgery in the Treatment of Medial Compartment Knee Osteoarthritis.

This study aimed to investigate the effect of partial fibula osteotomy combined with arthroscopic debridement surgery on the treatment of medial compartment knee osteoarthritis. From January 2013 to June 2016, 17 patients who suffered from medial compartment knee osteoarthritis were assigned to two groups: groups A (n = 5) and B (n = 12). Group A patients were treated with arthroscopic debridement surgery only, while group B patients received additional fibula osteotomy in addition to arthroscopic debridement operation. Visual analogue score (VAS) and hospital for special surgery (HSS) knee score were evaluated and compared between the two groups. Group B had significant reduction in the VAS after the procedure (3.1 ± 0.8) compared with that before the procedure (6.9 ± 1.0) or group A after surgery (5.4), respectively, p < 0.05. In contrast, the HSS knee score increased significantly in group B after the procedure (83.6 ± 2.5) compared with that before the procedure (63.0 ± 3.8) or group A after the surgery (68.2 ± 2.8), respectively, p < 0.05. Partial fibula osteotomy combined with arthroscopic debridement surgery is superior to arthroscopic debridement surgery only in the treatment of medial compartment knee osteoarthritis.

Effect of arthroscopic resection for discoid lateral meniscus on the axial alignment of the lower limb.

PURPOSE: This study was designed to investigate the changes in the lower limb axial alignment and knee joint function after arthroscopic resection of discoid lateral menisci. METHODS: Pre-operative and post-operative full-length weight-bearing radiographs of the lower limb were obtained from 60 patients with discoid lateral menisci from August 2015 to August 2016. Twenty-four patients were treated with meniscectomy and 36 cases were treated with meniscoplasty. The axial alignment of the lower limb was measured, and changes in the lower limb axial alignment before and after surgery were analyzed. The effects of differing degrees of meniscal resection on the lower limb axial alignment were compared and analyzed. Knee joint function on the affected side was scored using the Lysholm knee scoring, Tegner activity, and International Knee Documentation Committee (IKDC) subjective scales before surgery and one, six and 12 months after surgery. RESULTS: There were apparent changes in the lower limb axial alignment after surgery (p < 0.01). The changes were more conspicuous after a total meniscectomy than a meniscoplasty but were insignificant (p > 0.05). Intragroup comparisons of the Lysholm knee, IKDC, and Tegner scores before and after surgery revealed significant differences (p < 001). However, the differences were not significant between the two surgical approaches (p > 0.05). CONCLUSION: For those with considerable genu varum or genu valgum after surgery, individualized therapy should be developed to correct the lower limb axial alignment and to prevent articular cartilage degeneration. Arthroscopic resection of a discoid lateral meniscus greatly improves knee joint function.

[Arthroscopic treatment of tibial intercondylar eminence fractures in children with single Kirschner wire and suture avoiding epiphyseal line fixation technique].

OBJECTIVE: To discuss arthroscopic technique of single Kirschner wire and suture avoiding epiphyseal line fixation for tibial intercondylar eminence fracture and its clinical results. METHODS: From May 2008 to December 2012, 21 patients (13 males, 8 females, ranging in age from 6 to 14 years old) with tibial intercondylar eminence fracture were treated arthroscopically with single Kirschner wire and suture avoiding epiphyseal line fixation technique. According to Meyers and McKeever classification, 7 patients were type II, 10 patients were type III, and 4 patients were type IV. Active rehabilitation began at one week after operation. The patients were followed up for 10 to 30 months. X-ray films were taken to evaluate fracture healing at 1, 3, 6 months after operation; range of motion, the anterior drawer test, the lachman test and the Lysholm knee score were used to evaluate clinical effects. RESULTS: All fractures were healed without displacement at 6 weeks after operation. Anterior drawer test and the lachman test were both negative in all patients at 3 months after operation. Lysholm knee score was 95.5 ±2.5 at 6 months after operation, and postoperative X-ray film did not find epiphyseal line broadening or narrowing. CONCLUSION: Arthroscopic treatment for tibial eminence intercondylar fracture with single Kirschner wire and 8-shaped suture avoiding epiphyseal line fixation technique has many advantages, such as firm fixation,early mobilization, less invasive, less injury of physis and satisfactory effect.

Gene expression analysis in response to osmotic stimuli in the intervertebral disc with DNA microarray.

BACKGROUND: Intervertebral disc (IVD) cells experience a broad range of physicochemical stimuli under physiologic conditions, including alterations in their osmotic environment. At present, the molecular mechanisms underlying osmotic regulation in IVD cells are poorly understood. This study aims to screen genes affected by changes in osmotic pressure in cells of subjects aged 29 to 63 years old, with top-scoring pair (TSP) method. METHODS: Gene expression data set GSE1648 was downloaded from Gene Expression Omnibus database, including four hyper-osmotic stimuli samples, four iso-osmotic stimuli samples, and three hypo-osmotic stimuli samples. A novel, simple method, referred to as the TSP, was used in this study. Through this method, there was no need to perform data normalization and transformation before data analysis. RESULTS: A total of five pairs of genes ((CYP2A6, FNTB), (PRPF8, TARDBP), (RPS5, OAZ1), (SLC25A3, NPM1) and (CBX3, SRSF9)) were selected based on the TSP method. We inferred that all these genes might play important roles in response to osmotic stimuli and age in IVD cells. Additionally, hyper-osmotic and iso-osmotic stimuli conditions were adverse factors for IVD cells. CONCLUSIONS: We anticipate that our results will provide new thoughts and methods for the study of IVD disease.

Meta-analysis of Factor V Leiden G1691A polymorphism and osteonecrosis of femoral head susceptibility.

Testing for genetic risk associations between Factor V Leiden (FVL) and the osteonecrosis of femoral head (ONFH) is common, however, inconsistent results have been previously obtained. To summarize results on the association of FVL mutation polymorphism with ONFH in various populations and to calculate the overall genetic risk factors, we performed a search of electronic databases including PubMed, Elsevier Science Direct, Chinese National Knowledge Infrastructure and the Chinese Biomedical Database to identify published studies correlating the FVL mutation with ONFH. Statistical analysis was performed using Review Manager (RevMan) version 5.0 and Stata statistical software (version 10). We identified 57 titles and included 7 studies comprising 481 cases and 867 controls in this meta-analysis. The groups were pooled, and a significant association between FVL mutation and increased ONFH was found (OR=4.55, 95% CI, 2.75-7.52, P<0.00001). This meta-analysis demonstrated that FVL plays an important role in non-Asian populations. Large sample studies including different ethnic groups and age- and gender-matched groups, as well as multiple gene polymorphism detection should be considered to clarify the association of FVL mutation polymorphism and ONFH susceptibility in the future.

siRNAs target sites selection of ezrin and the influence of RNA interference on ezrin expression and biological characters of osteosarcoma cells.

Ezrin, one of the ezrin/radixin/moesin (ERM) protein family which act as membrane organizers and linkers between plasma membrane and cytoskeleton, has attracted much attention as a crucial factor for tumor metastasis. Overexpression of ezrin has been correlated with the metastatic potential of several cancers especially for osteosarcoma. Short interfering RNA (siRNA) downregulate gene expression through an enzyme-mediated process named RNA interference (RNAi). RNAi has rapidly come to be recognized as a powerful tool for the study of gene function and a potential target therapy. In the present study, the human osteosarcoma cell line MG63 was cultured. Three siRNAs targeting ezrin mRNA were designed by the multiple computational methods and then were sythesized. These siRNAs were transfected into osteosarcoma cells. Then the expression of ezrin mRNA and protein in osteosarcoma cells was detected. The cellular proliferation and apoptosis was evaluated. C726­U730, C1653­A1661 and G1749­A1771 were selected to be the suitable target sites through the multiple computational methods because of their ideal secondary structures and hybridization thermodynamics. siRNAs against G1749­A1771 downregulated the expression level of ezrin mRNA and protein, inhibit the cellular proliferation and promoted the cellular apoptosis effectively. There is a significant correlation between the multiple computational methods and the efficacy of the corresponding siRNAs. siRNAs targeting ezrin may have therapeutic potential as inhibitors of osteosarcoma metastasis.

[Total hip replacement with collum femoris preserving for the treatment of advanced stage of femoral head necrosis of young patients: a report of results of more than five years follow-up].

OBJECTIVE: To observe the results of total hip replacement with collum femoris preserving for the treatment of advanced stage of femoral head necrosis of youth. METHODS: From August 2002 to November 2009, 21 patients (28 hips) with advanced stage of femoral head necrosis were treated with total hip replacement with collum femoris preserving. Sixteen males (22 hips) and 5 females (6 hips) with an average age of 36 years (range from 26 to 51 years) were included. All patients were evaluated clinically using Harris score, the prosthesis components were assessed for position, loosening, bone resorption and other conditions with radiographs. RESULTS: Nineteen patients (26 hip) were followed up for mean 5 years and 7 months (ranging 5 years and 3 months to 7 years and 1 month), 2 patients were missed. The average Harris score increased from the preoperative average 48.5 to 90.2. The leg-length discrepancy (the difference was less than 2 cm) occurred in 3 cases. No thigh pain and revision. CONCLUSION: Total hip arthroplasty with collum femoris preserving is one of the best choices for the treatment of advanced stage of femoral head necrosis of young patients with good midterm outcome.

Preparation of amide-amine bifunctionalized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) films to improve chondrocyte adhesion.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) films were covalently functionalized with amide and amine domains, with the aim to improve chondrocyte adhesion. X-ray photoelectron spectroscopy spectra confirmed that amide and amine groups were present on the film surface. Scanning electron microscopy results showed that the amide-amine bifunctionalized PHBV films possessed a loose layer on the surface or formed pore structure. The crystallization properties were characterized by differential scanning calorimetry and wide-angle X-ray diffraction. The amide-amine bifunctionalized PHBV films had two endotherm peaks in the 60-80 degrees C and 130-170 degrees C regions, which suggested that imperfect PHBV crystals were formed owing to the penetration of the grafted amide-amine chains. Water-swelling percentage of the amide-amine bifunctionalized PHBV films increased with increasing polyacrylamide grafting percentage, especially the ability to hold water inside films. Sheep chondrocytes were cultured on the amide-amine bifunctionalized PHBV film and the PHBV film, respectively. Cell studies revealed that the bifunctionalized PHBV film was more favourable for chondrocytes adhesion than the PHBV film. These results suggest promising application of the amide-amine bifunctionalized PHBV film in cartilage tissue engineering.

Surface engineering of PHBV by covalent collagen immobilization to improve cell compatibility.

Covalent immobilization of collagen onto poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) film was achieved to improve its cell compatibility. Amide groups photografted on PHBV films were initially converted into amine groups through Hofmann degradation and collagen was then chemically bonded to amine groups, consequently forming the amide, amine, and collagen-modified PHBV. The structures of these modified PHBV films were confirmed by ATR-FTIR, XPS, and SEM analyses. Compared with that of PHBV film, surface wettability of the modified PHBV films enhanced remarkably. In particular, water contact angle of the collagen-modified PHBV film decreased from 65.0 degrees to 2.1 degrees within 130 s. Sheep chondrocytes cultured on PHBV and modified PHBV films were evaluated by cell adhesion test, MTT assay, and morphological observation under SEM. Results showed that the collagen-modified PHBV film had better cell adhesion and proliferation than other modified PHBV films and PHBV film. Chondrocytes on the collagen-modified PHBV film adhered through filopodia, spread by cytoplasmic webbing, and formed cells layer earlier than other modified ones, indicating that the collagen-modified PHBV is a promising biomaterial for cartilage tissue engineering.

[Arthroscopic diagnosis and treatment of posttraumatic chronic ankle pain].

OBJECTIVE: To evaluate the arthroscopic diagnosis and treatment of the chronic ankle pain after injury. METHODS: From April 1999 to June 2008, 39 patients with posttraumatic chronic ankle pain were treated. The mean duration between the initial injury and treatment was 18 months (2 months to 11 years). There were 15 males and 24 females with a mean age of 32 years (15 to 58 years). All the patients were treated with arthroscopic debridement. The preoperative and postoperative ankle functions were evaluated by the AOFAS (the American Orthopaedic Foot and Ankle Society) Clinical Rating System for the ankle-hindfoot. RESULTS: Twenty-six patients had osteochondral lesions. Impingement syndrome in ankle was observed in 21 patients. The impingement tissue included synovial hypertrophy in 3 patients, ligament injury in 10 patients (7 patients had anterior talofibular ligament injury and 3 patients had anteroinferior tibiofibular ligament injury), meniscoid tissue in 6 patients, pathological labrum in 3 patients. All the patients were followed up with an average of (14.2+/-8.4) months (ranged from 5 to 36 months). The AOFAS scores increased significantly from pre-operative (59.7+/-16.9) to post-operative (68.8+/-21.2), and it was obvious in relieving pain, which was pre-operative (22.8+/-10.0) and post-operative (29.5+/-12.1). CONCLUSION: Arthroscopy can be used to diagnose the cause of chronic ankle pain after injury. Furthermore, arthroscopic debridement was useful to relieve the pain and improve the joint function, and it is appropriate for patients who had no fractures and dislocations.

[Different adhesion rate of sheep BMSCs on copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate before and after photografting modification in vitro].

OBJECTIVE: To evaluate the biocompatibility of the sheep BMSCs cultured on the surface of photografting modified copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV). METHODS: BMSCs were isolated from bone marrow of the posterior iliac crest of a 6-month old sheep by whole marrow adherent culture method. The 3rd passage BMSCs were seeded onto modified PHBV and conventional PHBV films, or three-dimension scaffolds. Cell-adhesion rates were calculated by hemocytometer at 1, 2 and 6 hours after seeded. Cell morphology was examined by scanning electron microscope when the BMSCs were cultured for 3 days, 1 week and 3 weeks. Cell cycle was analyzed by flow cytometry at 5 days after seeded. The content of protein in BMSCs was determined by BCA assay and the content of DNA was quantified by Hoechst 33258 assay at 4, 8 and 12 days after seeded. RESULTS: At 1 hour after seeded, cell-adhesion rate on modified PHBV films (52.7% +/- 6.0%) was significantly higher than that of conventional PHBV films (37.5% +/- 5.3%) (P < 0.05); At 2 and 6 hours after seeded, cell-adhesion rate of modified PHBV films was similar to that of PHBV films (P > 0.05). The surface of modified PHBV film was rougher. In the early culture stage, more cells adhered to modified PHBV and the cells displayed much greater spreading morphology. Furthermore, ECM on modified PHBV were richer. There were no significant differences between the trial team and the control on the cell cycle and the content of DNA and protein of BMSCs (P > 0.05). CONCLUSION: Photografting modification on PHBV can promote BMSCs' adhesion and enhance their biocompatibility.

Comparative analysis of serum proteomes: discovery of proteins associated with osteonecrosis of the femoral head.

No means exist to evaluate the activity status, turnover, and prognosis of idiopathic osteonecrosis of the femoral head (IONFH) except for X-ray evidence of segmental collapse as a very good marker for prognosis. Moreover, the only current method for diagnosis of this disease is through physical examination and diagnostic imaging results, and no serum biochemical markers exist. A comparative analysis of serum proteomes was performed to discover proteins associated with osteonecrosis of the femoral head. Two-dimensional electrophoresis (2-DE) patterns of human sera from 10 patients with IONFH and 10 normal subjects were analyzed. The differentially expressed spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and 7 proteins were found. The expression levels of tissue-type plasminogen activator (t-PA), bone-carboxyglutamate protein (BGP), c-sis, and an unknown protein were downregulated in the sera of patients with IONFH, whereas the other 3 proteins, including plasminogen activator inhibitor type 1 (PAI-1), crosslaps, and anti-p53 antibody, were upregulated. To examine their applicability as diagnostic markers, levels of the 6 identified proteins in serum were validated from patients with IONFH, osteoarthritis (OA), rheumatoid arthritis (RA), and fracture using the enzyme-linked immunosorbent assay (ELISA) method. It was found that only serum levels of t-PA, PAI-1, crosslaps, and anti-p53 antibody in patients with IONFH were always significantly different from those in patients with OA, RA, and fracture. These results suggest that serum levels of t-PA, PAI-1, crosslaps, and anti-p53 antibody could be used as noninvasive diagnostic biomarkers for IONFH.

[Surgical treatment of lumbar spinal stenosis associated with unstable degenerative spondylolisthesis].

OBJECTIVES: To assess surgical treatment of lumbar spinal stenosis associated with unstable degenerative spondylolisthesis. METHODS: In 86 patients with lumbar spinal stenosis associated with unstable degenerative spondylolisthesis. (30 men and 56 women, aged from 30 to 77 years), 63 patients complained of lower back pain with both lower extremity pain, 10 patients pain in one leg, and 13 patients only lower back pain. Seventy-two of these patients complained of intermittent claudication, with a walking distance ranging from 10 to 1 000 m. Thirty-two patients had some changes in sensation, motion and reflexes of the foot. According to White' critera, all patients showed dynamic instability of the lesion. Meyerding criteria showed degree 1 in 79 patients, and degree 2 in 7. CT scan was made in 56 patients, MRI in 24 and MRM in 6 before operation. Myelography was performed in 61 patients, and CTM in 6. Stenosis and spondylolisthesis located between L(4) and L(5) in 49 patients, between L(3) and L(4) in 6, between L(5) and S(1) in 25, between L(3) and L(4) and between L(4) and L(5) in 2, and from L(3) to S(1) in 4. The patients with pathological spondylolisthesis were excluded. Lateral recess stenosis of one leg was observed in 10 patients, lateral recess of both legs in 22, and central canal stenosis in 54, of whom 12 patients were associated with protrusion of the lumbar disc. Decompression and autograft with iliac bone and various internal fixation were performed in all patients. RESULTS: The patients were followed up from 8 months to 13 years, longer than 1 year (average 5.6 years) in 81 patients. According to Amundsen et al, excellent results were obtained in 78 patients, good in 5, and fair in 3. Spondylolisthesis was completely reduced in 70 patients of degree 1 (89.9%), and in 6 patients of degree 2 (85.7%). No patient showed slippage aggravated. 74 patients gained bone graft fusion within 3 months and 10 patients within 6 months. Two patients showed pseudoarthrosis during the follow-up. Complications included internal fixation breakage in 1 patient, and delayed infection in 1. CONCLUSIONS: Complete decompression and bone graft fusion are the key to treatment. Decompression and internal fixation improve the symptoms of patients with lumbar spinal stenosis associated with spondylolisthesis. Transpedicle instrumentation can reduce spondylolisthesis and maintain the physical curve of the lumbar.

[Diagnosis and treatment of cervical disc calcification in children].

OBJECTIVES: To investigate the diagnosis and treatment cervical disc calcification in children. METHODS: 13 children with cervical disc calcification were analysed retrospectively. Cervical pain was observed after influenza in 5 children, suddenly cervical pain in 3, sudden wryneck in 3 cases. Two children with this disease were accidentally found after injury. RESULTS: 14 calcifications of cervical disks were found in 13 children. Clinical symptoms disappeared after symptomatic management. Calcification disappeared in 5 months. CONCLUSIONS: Cervical disc calcification in children is a kind of benign self-limited disease. Correst understanding of pathophysiologic course of this disease helps to avoid unnecessary surgery.