Influence of cement-augmented pedicle screws with different volumes of polymethylmethacrylate in osteoporotic lumbar vertebrae over the adjacent segments: a 3D finite element analysis.

BACKGROUND: Polymethylmethacrylate (PMMA) is commonly used for cement-augmented pedicle screw instrumentation (CAPSI) to improve the fixation stability and reduce the risk of screw loosening in the osteoporotic thoracolumbar spine. Biomechanical researches have shown that various dose of cement (1-3 ml) can be injected to enhance screw stability. To date, there have been no studies on the relationship between adjacent segment degeneration and the volume of PMMA. This study aimed to explore the influence of CAPSI with different volumes of PMMA in osteoporotic lumbar vertebrae over adjacent segments by using finite element analysis. METHODS: Seven different finite element models were reconstructed and simulated under different loading conditions, including (1) an intact model, (2) three single-level CAPSI models with different volumes of PMMA (1, 1.73, and 2.5 ml), and (3) three double-level CAPSI models with different volumes of PMMA (1, 1.73, and 2.5 ml). To improve the accuracy of the finite element analysis, the models of the injectable pedicle screw and bone cement were created by using a three-dimensional scanning machine and the CAPSI patient's CT data, respectively. The range of motion (ROM), the stress of intervertebral discs, and the stress of facet in the adjacent segment were comparatively analyzed among the different models. RESULTS: The ROMs of the different segments were compared with experimental data, with good agreement under the different load conditions (21.3°, 13.55°, 13.99°, and 6.11° in flexion, extension, bending, and rotation at L3-S1 level, respectively). Compared with the intact model, the ROM, disc stresses, and facet stress in adjacent segments were found to be higher in the six operative models. Otherwise, with a larger volume of PMMA injected, the ROM, disc stresses, and facet stress slightly increased at the adjacent segment. However, the differences were insignificant with the biggest difference less than 3.8%. CONCLUSIONS: CAPSI could increase the incidence of disk degeneration in the adjacent segment, while within a certain range, different volumes of PMMA provided an approximate impact over the adjacent segment degeneration.

Pedicle Screw Fixation in Single-Level, Double-Level, or Multilevel Posterior Lumbar Fusion for Osteoporotic Spine: A Retrospective Study with a Minimum 2-Year Follow-Up.

BACKGROUND: Pedicle screw loosening is a common postoperative complication for osteoporotic patients, and several studies have identified the important role of fusion length in internal fixation failure, but the relationship between the number of fusion segments and the potential risks remains unclear. This study aimed to investigate the rate and risk factors of screw loosening in osteoporotic patients with different levels of degenerative lumbar disease. METHODS: The total cohort of 217 patients was divided into 3 groups according to the different fusion levels: single-level (group A; 100 cases), double-level (group B; 73 cases), and multilevel group (group C; 44 cases). Patient baseline demographic characteristics and assessments with a visual analog scale (VAS) and the Oswestry Disability Index (ODI) before operation and at the last follow-up were compared among the 3 groups. RESULTS: Compared with preoperative values, VAS and ODI scores at the last follow-up were significantly improved in all 3 groups. Operative time, blood loss, length of hospital stay, screw loosening rate, fusion rate, and VAS and ODI scores at the last follow-up obviously increased with the increasing number of fusion segments (group C> group B> group A). Of note, all the screw loosening was observed in cranial and caudal vertebra. Furthermore, multivariate logistic regression analysis identified lumbosacral fixation, larger pelvic incidence (PI)-lumbar lordosis (LL) difference (PT-LL), and greater postoperative pelvic tilt (PT) as independent predictors of screw loosening. However, sex, bone mineral density, body mass index, LL, sacral slope, PI, the change in LL, and preoperative PT were not relevant to screw loosening (P > 0.05). CONCLUSIONS: Owing to the high rate of screw loosening in cranial and caudal vertebra, osteoporotic patients with double-level or multilevel pedicle screw fixation benefited less than those with single-level pedicle screw fixation. Larger PI-LL, larger PT, and lumbosacral fixation are other risk factors for screw loosening. An instrument with stronger holding strength at cranial and caudal pedicle screws is recommended for those high-risk patients.

Nrf2 protects human lens epithelial cells against H2O2-induced oxidative and ER stress: The ATF4 may be involved.

Our previous study has shown heme oxygenase-1 (HO-1) protects human lens epithelial cells (LECs) against H2O2-induced oxidative stress and apoptosis. Nrf2, the major regulator of HO-1, is triggered during the mutual induction of oxidative stress and ER stress. In response to ER stress, unfolded protein response (UPR) serves as a program of transcriptional and translational regulation mechanism with PERK involved. Both Nrf2 and ATF4 are activated as the downstream effect of PERK signaling coordinating the convergence of dual stresses. However, the ways in which Nrf2 interacting with ATF4 regulates deteriorated redox state have not yet been fully explored. Here, the transfected LECs with Nrf2 overexpression illustrated enhanced resistance in morphology and viability upon H2O2 treatment condition. Intracellular ROS accumulation arouses ER stress, initiating PERK dependent UPR and inducing the downstream signal Nrf2 and ATF4 auto-phosphorylation. Further, converging at target promoters, ATF4 facilitates Nrf2 with the expression of ARE-dependent phase II antioxidant and detoxification enzymes. According to either Nrf2 or ATF4 gene modification, our data suggests a novel interaction between Nrf2 and ATF4 under oxidative and ER stress, thus drives specific enzymatic and non-enzymatic reactions of antioxidant mechanisms maintaining redox homeostasis. Therapies that restoring Nrf2 or ATF4 expression might help to postpone LECs aging and age-related cataract formation.

Overexpression of the receptor-like protein kinase genes AtRPK1 and OsRPK1 reduces the salt tolerance of Arabidopsis thaliana.

AtRPK1 (AT1G69270) is a leucine-rich repeat receptor-like protein kinase (LRR-RLK) gene in Arabidopsis thaliana. The rice gene Os07g0602700 (OsRPK1) is the homolog of AtRPK1. AtRPK1 and OsRPK1 were overexpressed and the expression of AtRPK1 was inhibited by RNAi in A. thaliana. The functional results showed that the degrees of salt tolerance of the 35S:RPK1 A. thaliana plants were significantly lower than that of the control plants. The AtRPK1-RNAi A. thaliana plants exhibited higher salt tolerance than the wild-type plants (Col). The subcellular localisation results showed that the RPK1 proteins were mainly distributed on the cell membrane and that the overexpressed AtRPK1 proteins exhibited a significantly clustered distribution. The physiological analyses revealed that the overexpression of the RPK1 genes increased the membrane permeability in the transgenic A. thaliana plants. In response to salt stress, these plants exhibited an increased Na(+) flux into the cell, which caused greater damage to the cell. The real-time quantitative PCR analysis showed that the expression of the P5CS1 gene was inhibited and the SOS signalling pathway was blocked in the 35S:AtRPK1 A. thaliana plants. These effects at least partially contribute to the salt-sensitive phenotype of the 35S:RPK1 plants.

[Effects of interleukin 21 on anti-leukemia activity of cytotoxic T lymphocytes induced by dendritic cells].

This study was aimed to explore the effects of interleukin 21 (IL-21) on the anti-leukemia activity of cytotoxic T lymphocytes (CTL) induced by dendritic cells (DCs) in vitro. The peripheral mononuclear cells from leukemia patients in complete remission were cultured with the specific cytokines to induce the production of DCs. The DCs loaded with RNA from autologous leukemic cells as antigen, and co-cultured with autologous T lymphocytes to get leukemia specific CTL. The cytotoxic activity of CTL against autologous leukemic cells was measured by LDH release method. The concentration of IFN-gamma and TNF-alpha in the culture supernatant was measured by enzyme immunoassay. The effects of IL-21 on the mature DCs were also studied by the measurement of the phenotype of DC and the allogenic mixed lymphocytic reactions induced by DCs. Experiments were divided into 2 groups: test group in which IL-21 (200 ng/ml) was added in coculture of DC/CTL and control group in which no IL-21 (200 ng/ml) was added. The results showed that when cultured with IL-21, the quantity of CTL increased from (56.73 +/- 10.21)% (control group) to (73.43 +/- 18.01)% (p < 0.01); The concentration of IFN-gamma and TNF-alpha in the culture supernatant increased from (154.91 +/- 67.20) ng/L (control group) to (310.62 +/- 141.15) ng/L (p < 0.01) and from (8.77 +/- 5.09) microg/L (control group) to (15.25 +/- 6.56) microg/L (p < 0.01) respectively. At the effector: target ratio of 20:1, the cytotoxic activity against autologous leukemic cells by CTL increased from (50.22 +/- 5.07)% (control group) to (75.38 +/- 9.47)% (p < 0.01). IL-21 had neither effect on the phenotype (CD1a, CD83, CD86, CD80 and HLA-DR) of mature DCs nor the allogeneic mixed lymphocytic reactions induced by DCs. It is concluded that IL-21 can strengthen the proliferation of CTL, and improve the production of IFN-gamma and TNF-alpha, thus enhance the anti-leukemia activity of CTL. Nevertheless, there is no effect of IL-21 on the function of mature DCs. These data indicate that IL-21 has a potential clinical value in the enhancement of anti-leukemia immunotherapy.

[Wilms' tumor-1 gene expression in myelodysplastic syndrome and its changes in the process of myelodysplastic syndrome transforming into acute leukemia].

OBJECTIVE: To observe expression of Wilms' tumor-1 (WT1) gene in the different subtypes of myelodysplastic syndrome (MDS), and to explore the regularity of expression of WT1 gene in the process of MDS transforming into acute leukemia (AL). METHODS: The method of reverse transcriptase-polymerase chain reaction (RT-PCR) was used, the levels of WT1 gene's presentation in different types of montagers of MDS were analyzed, and the relationship between the level and the clinical characteristic was analyzed. At the same time, the expression of WT1 gene in AL patients, post-MDS-AL patients and normal controls were examined. RESULTS: The positive rate of WT1 gene expression in 49 patients with MDS was 22.4 percent (11/49), refractory anemia (RA) was 0(0/13), RA with excess of blast (RAEB) was 25.0 percent (6/24); RAEB in transformation (RAEB-t) was 41.7 percent (5/12). The positive rates of WT1 expression were gradually increased in three types of MDS (P<0.05 and P<0.01). The positive rates of WT1 expression were higher in AL and post-MDS-AL patients (48.5 percent, 32/66 and 50.0 percent, 4/8) than that in MDS patients (P<0.01). There was no expression of WT1 gene in normal control. CONCLUSION: There is a relatively high expression rate of WT1 gene in RAEB, RAEB-t of MDS, but relatively low expression rate in RA. The method of RT-PCR, is high sensitiveness and specificity, can trustful be used in the progression of monitoring MDS' progression and its transformation into AL.