Pilose antler peptide potentiates osteoblast differentiation and inhibits osteoclastogenesis via manipulating the NF-κB pathway.

Bones are inflexible yet ever-changing metabolic organs, and bone homeostasis is maintained through two delicately regulated processes: bone construction and bone reabsorption. An imbalance in bone metabolism is linked to most orthopedic diseases, including osteoporosis and rheumatoid arthritis. Importantly, tumor necrosis factor-α (TNF-α) blocks osteoblast differentiation and stimulates osteoclast formation, resulting in delayed deposition of new bone and accelerated bone resorption, especially in rheumatoid arthritis patients with inflammatory conditions. Pilose antler peptide (PAP) isolated and purified from deer antlers has been shown to have beneficial effects on chronic inflammation. In the present study, we studied the impact of PAP on osteoblast differentiation and evaluated the regulatory mechanism, with particular emphasis on the effect of PAP on TNF-α-mediated NF-κB signaling. Mouse primary osteoblast cells were activated with bone morphogenetic protein-2 (BMP-2) for osteoblast differentiation. A significant stimulatory effect of PAP in osteoblastogenesis was observed using ALP activity and Alizarin Red S staining assays. Meanwhile, PAP significantly rescued TNF-α-induced impairment of osteoblast formation as well as mineralization. Furthermore, we found a similar trend upon analyzing osteoblast-specific gene expression. PAP significantly rescued TNF-α-mediated decrease in expression of osteoblast-specific genes. A molecular mechanism assay indicated that PAP significantly inhibited TNF-α-mediated stimulation of NF-κB signaling activity, as well as nuclear translocation of its subunit p65. Moreover, over-expression of p65 reversed the stimulatory effects of PAP on osteoblast differentiation. Furthermore, we also identified that PAP dose dependently inhibit osteoclastogenesis, and this effect might be achieved via suppressing NF-κB activity. In summary, this study shows that PAP promotes osteoblast differentiation and blocks TNF-α-mediated suppression of osteoblastogenesis in vitro via the NF-κB/p65 pathway, as well as inhibits osteoclastsogenesis in vitro. Therefore, PAP, a novel drug with both antiresorptive and osteoanabolic activity, shows therapeutic potential as an alternative treatment for osteolytic diseases, including rheumatoid arthritis and osteoporosis.

[A comparison of results between percutaneous transforaminal endoscopic discectomy and fenestration discectomy for lumbar disc herniation in the adolscents].

OBJECTIVE: To compare the preliminary clinical outcomes of percutaneous transforaminal endoscopic discectomy (PTED) and fenestration discectomy (FD) for lumbar disc herniation in the adolscents and further to summarize the clinical experience. METHODS: The data of 56 patients with single segment lumbar disc herniation who were adopted by our department from January 2011 to December 2013 were retrospectively studied. All patients were divided into 2 groups, including 30 patients undergoing PTED and 26 patients undergoing FD respectively. The factors including the length of skin incision, amount of intraoperative bleeding, operation time and duration of hospitalization were compared. Pfirrmann grading system was used for assessment of lumbar disc degeneration preoperatively and 1 year later. The visual analogue scale (VAS), Oswestry Disability Index (ODI) and Japanese Orthopedic Association (JOA) scores were used to measure the clinical outcomes. RESULTS: There were significant differences in the observation factors such as the skin incision length, amount of intraoperative bleeding, operation time and duration of hospitalization between the PTED and FD groups (P < 0.05). After surgery, the patients in both groups were followed up for 12 months on average respectively. The postoperative lumbar disc degeneration in PTED group was decreased than that of in FD group. The postoperative VAS scores, ODI and JOA scores at each follow-up time point in both groups were significantly improved when compared with the preoperative ones (P < 0.05). There were no statistically significant differences between the 2 groups in the JOA score improvement rate (P > 0.05). According to 'the modified MacNab criteria, there were no statistically significant differences between the 2 groups in the excellent and good rate (P > 0.05). CONCLUSIONS: The preliminary clinical efficacy of both PTED and FD in the treatment of single segment lumbar disc herniation in the adolscents is satisfactory. However, PTED is a better minimally invasive surgical method with such advantages as less trauma, less blood loss, early function recovery, less effect on lumbar spinal stability and so on. The short-term outcomes of PTED are similar to that of FD.

Related factors of severe osteoporotic vertebral compression fracture and clinical outcomes of percutaneous kyphoplasty: A retrospective study.

BACKGROUND: Osteoporosis is the most common disease in postmenopausal women and the elderly, which can lead to vertebral compression fracture. OBJECTIVE: To investigate the related factors of severe osteoporotic vertebral compression fracture (SOVCF) and evaluate the long-term outcomes of percutaneous kyphoplasty (PKP) for treating SOVCF through comparison with mild OVCF (MOVCF). METHODS: From September 2015 to March 2019, 294 osteoporotic vertebral compression fracture (OVCF) patients treated with PKP were analyzed. Compression of the anterior margin of the fractured vertebral body beyond 2/3 of the original height was defined as SOVCF. Baseline data, clinical and imaging findings before and after surgery and at the last follow-up were recorded. Numerical Rating Scale (NRS) was used to evaluate low back pain, the Oswestry Disability Index (ODI) was used to evaluate activity of daily life. Anterior vertebral height (AVH) and local kyphosis angle (LKA) was used to evaluate radiographic outcomes. During the follow-up, patients with recurrent back pain were examined by MRI to identify new fractures and the incidence of adjacent vertebral fracture (AVF) was recorded. Age, sex, body mass index (BMI), dual energy X-ray absorptiometry based T value, duration of symptom, history of trauma, steroid use, and fracture site were collected for univariate logistic regression analysis Variables with a P-value of less than 0.05 were then included in multivariate analysis to determine the related factors for SOVCF. RESULTS: Logistic regression analysis indicated that longer duration of symptom (OR = 1.109, 95%CI: 1.038-1.185, P= 0.002), lower T value (OR = 0.332, 95%CI: 0.139-0.763, P= 0.001), and steroid use (OR = 31.294, 95%CI: 1.020-960.449, P= 0.049) were related factors of SOVCF. Compared with the MOVCF group, the SOVCF group had longer operation time (57.3 ± 13.51 minutes vs 44.9 ± 8.13 minutes, P< 0.001), more radiation exposure (39.9 ± 7.98 times vs 25.5 ± 4.01 times, P< 0.001), and higher cement leakage rate (55.81% vs 18.73%, P< 0.001). At the last follow-up, the SOVCF group had higher NRS (2.28 ± 0.85 vs 1.30 ± 0.71, P< 0.001), and ODI (16.23 ± 4.43 vs 12.88 ± 3.34, P< 0.001). After operation and at the last follow-up, the SOVCF group had higher LKA and lower AVH (all P< 0.05). The AVF rate at the last follow-up was higher in the SOVCF group at the last follow-up (4.78% vs 18.60%, P< 0.001). CONCLUSION: Lower T value, longer duration of disease, and steroid use were related factors of SOVCF. Compared with MOVCF, PKP for SOVCF had longer operation time, more radiation exposure, and higher cement leakage rate, and the long-term outcomes were worsen.

[Efficacy evaluation of percutaneous vertebroplasty via an extra-pedicular approach for osteoporotic compression fracture].

OBJECTIVE: To evaluate the effects of relieving pains and restoring vertebral heights of percutaneous balloon kyphoplasty by extra-pedicular approach as a minimally invasive treatment in patients with painful osteoporotic vertebral compressive fractures (OVCF). METHODS: A retrospective analysis was conducted for 96 consecutive patients. There were 64 females and 32 males with a mean age 67 years (range: 55 - 82). Symptomatic levels were identified by correlating their clinical presentations with the findings of magnetic resonance imaging (MRI). The interval between onset of symptoms and surgical intervention ranged from 2 days to 4 months. A total of 118 levels (56 thoracic, 62 lumbar) were treated in this cohort. Immediate and postoperative 3-month follow-up visits were conducted. Visual analog scale (VAS) pain scores, preoperative and postoperative anterior, midline vertebral heights for fractured vertebrae were measured on lateral radiographs to evaluate the procedural outcomes. RESULTS: There was swift pain relief associated with evident augmentation in weight-bearing resistance. Pain decreased from 8.1 to 2.1 points. Through kyphoplasty, the anterior, midline vertebral heights of 118 fractured vertebral bodies increased up to (75.83 ± 19.84)% and (71.23 ± 21.45)% respectively. None of them had worsening of fracture-induced narrowing of spinal canal. No device-related major complications occurred. CONCLUSION: Percutaneous kyphoplasty through an extra-pedicular approach results in immediate clinical improvement of mobility and pain relief. It safely increases vertebral body height and quickly returns geriatric patients to higher activity levels, increased independence and better quality-of-life. And its short-term outcomes are excellent.

Percutaneous Functional Spinal Unit Cementoplasty versus Posterior Spinal Fixation with Vertebroplasty for Symptomatic Chronic Osteoporotic Vertebral Fractures: A Retrospective Study with a 2-Year Follow up.

PURPOSE: To compare the clinical efficacy of percutaneous functional spinal unit cementoplasty (PFSUP) and posterior spinal fixation combined with vertebroplasty (PSF + VP) for the treatment of symptomatic chronic osteoporotic vertebral fractures (SCOVFs). METHOD: Thirty-one patients with SCOVFs were included in this retrospective study and divided into PFSUP (n = 14) and PSF + VP (n = 17) groups. Visual analog scores (VAS) and Oswestry Disability Index (ODI) were recorded before and after surgery and at the last follow-up. Besides, the local kyphosis angle (LKA) and sagittal vertical axis (SVA) were measured. The operation duration, number of X-ray exposures, amount of blood loss, bed rest duration, hospitalization duration, and presence of complications were recorded. RESULT: The VAS, ODI, LKA, and SVA after surgery and at the last follow-up were significantly improved in both groups compared to preoperative measurements. The PFSUP group experienced shorter operation duration (78.2 ± 13.1 vs. 124.7 ± 14.7, p < 0.001), less blood loss (31.1 ± 8.1 vs. 334.7 ± 70.9, p < 0.001), more X-ray exposures (92.1 ± 14.3 vs. 29.4 ± 5.5, p < 0.001), shorter bed rest duration (12.4 ± 3.8 vs. 43.4 ± 10.0, p < 0.001), shorter hospitalization (6.6 ± 2.4 vs. 10.9 ± 2.7, p < 0.001), lower complication rate (28.5% vs. 64.7%, p < 0.05), and higher cement leakage rate (42.9% vs. 5.8%, p < 0.05) than the PSF + VP group. CONCLUSION: During the treatment of SCOVFs, the combination of PFSUP and PSF + VP can restore spinal stability, improve kyphosis, and relieve pain. PFSUP can reduce blood loss and complications, early mobilization, and shorten the hospital stay, but it is associated with a higher cement leakage rate and more radiation exposure.

Clinical outcomes with second injection after insufficient bone cement distribution in unilateral kyphoplasty for osteoporotic vertebral compressive fracture: a cohort retrospective study.

BACKGROUND: Bone cement distribution is an important factor affecting pain relief and long-term prognosis of osteoporotic vertebral compression fracture (OVCF) treated with vertebral augmentation. Unilateral percutaneous kyphoplasty (PKP) is the most common procedure, and insufficient bone cement distribution is more common than bilateral PKP. However, effective remedies are remain lack. In this study, sufficient cement distribution was achieved by adjusting the working channel followed by second cement injection as a remedy in cases with insufficient cement distribution, and the purpose was to evaluate the clinical outcomes by a retrospective cohort study. METHODS: From July 1, 2017 to July 31, 2020, OVCF patients treated with unilateral PKP were included in this retrospective cohort study. According to the bone cement distribution (insufficient cement distribution was confirmed when the cement did not exceed the mid line of the vertebral body in frontal film or/and the cement did not contact the upper/lower vertebral endplates in the lateral film.) and whether second injection was performed during surgery, the patients were divided into three groups. Insufficient group: patients with insufficient cement distribution confirmed by fluoroscopy or postoperative x-ray. Second injection group: patients with insufficient cement distribution was found during the procedure, and second injection was performed to improve the cement distribution. CONTROL GROUP: patients with sufficient cement distribution in one injection. The Primary outcome was cemented vertebrae re-collapse rate. The secondary outcomes included operative time, radiation exposure, cement leakage rate, VAS, ODI, and adjacent vertebral fracture rate. RESULTS: There are 34 cases in insufficient group, 45 cases in second injection group, and 241 cases in control group. There was no significant difference in baseline data and follow-up time among the three groups. PRIMARY OUTCOME: The injured vertebrae re-collapse rate of insufficient group was significantly higher than that of second injection group (42.22% vs 20.59%, P = 0.000) and control group (42.22% vs. 18.26%, P = 0.000). Kaplan-Meier survival analysis showed that there was no significant difference in the survival time between second injection group and control group (P = 0.741, Log-rank test), both of which were significant less than that in insufficient group (P = 0.032 and 0.000, respectively). SECONDARY OUTCOMES: There was no significant difference in VAS score and ODI after operation between second injection group and control group, both of which were superior to those in insufficient group (P = 0.000). At the final follow-up, there was no significant difference in VAS and ODI among the three groups (P > 0.05). The operation time of second injection group was significantly higher than that of insufficient group (53.41 ± 8.85 vs 44.18 ± 7.41, P = 0.000) and control group (53.41 ± 8.85 vs 44.28 ± 7.22, P = 0.000). The radiation exposure of the second injection group was significantly higher than that of insufficient group (40.09 ± 8.39 vs 30.38 ± 6.87, P = 0.000) and control group (40.09 ± 8.39 vs 31.31 ± 6.49, P = 0.000). The cement leakage rate of second injection group (20.59%) was comparable with that of insufficient group (24.44%) and control group (21.26%) (P = 0.877). The length of hospital stay of the second injection group (4.38 ± 1.72) was comparable with that of insufficient group (4.18 ± 1.60) and control group (4.52 ± 1.46) (P = 0.431). CONCLUSIONS: When cement distribution is insufficient during unilateral PKP, second injection may relieve early pain, reduce the incidence of cemented vertebral re-collapse and adjacent vertebral fracture, without increasing the cement leakage rate, although this procedure may increase the operation time and radiation exposure.

A Precise qNMR Method for the Rapid Quantification of Lot-to-Lot Variations in Multiple Quality Attributes of Pentosan Polysulfate Sodium.

Pentosan polysulfate sodium (PPS) is an orphan drug with anticoagulant activity. PPS is prepared from the chemical processing of xylan extracted from beechwood tree to yield a mixture of 4-6 kDa polysaccharides. The chain is mainly composed of sulfated xylose (Xyl) with branched 4-O-methyl-glucuronate (MGA). During generic drug development, the quality attributes (QAs) including monosaccharide composition, modification, and length need to be comparable to those found in the reference list drug (RLD). However, the range of QA variation of the RLD PPS has not been well characterized. Here, multiple PPS RLD lots were studied using quantitative NMR (qNMR) and diffusion ordered spectroscopy (DOSY) to quantitate the components in the mixture and to probe both inter- and intra-lot precision variability. The DOSY precision assessed using coefficient of variation (CV) was 6%, comparable to PPS inter-lot CV of 5%. The QAs obtained from 1D qNMR were highly precise with a precision CV < 1%. The inter-lot MGA content was 4.8 ± 0.1%, indicating a very consistent botanical raw material source. Other process-related chemical modification including aldehyde at 0.51 ± 0.04%, acetylation at 3.3 ± 0.2% and pyridine at 2.08 ± 0.06%, varied more than MGA content. The study demonstrated that 1D qNMR is a quick and precise method to reveal ranges of variation in multiple attributes of RLD PPS which can be used to assess equivalency with generic formulations. Interestingly, the synthetic process appeared to introduce more variations to the PPS product than the botanical source of the material.

[Posterior interbody fusion versus improved transforaminal lumbar interbody fusion in segmental spinal fixation for aged spondylolisthesis with lumbar spinal canal stenosis].

OBJECTIVE: To assess the clinical and radiographic outcomes of posterior lumbar fixation and posterior interbody fusion or improved transforaminal lumbar interbody fusion for Meyerding grade II/III spondylolisthesis so as to address the suitability of a dynamic stabilization. METHODS: A total of 28 consecutive patients underwent posterior lumbar fixation and posterior interbody fusion or improved transforaminal lumbar interbody fusion for Meyerding grade II/III spondylolisthesis. Among them, 13 patients underwent posterior interface fusion (PLIF) and pedicle screw fixation. And improved transforaminal lumbar interbody fusion (ITLIF) and placement of the same system were performed in 15 patients. Their clinical, economic, functional, and radiographic data were recorded both pre- and postoperatively. RESULTS: The average changes of economic and functional scores on the Prolo scale were 1.36 and 1.48 respectively. In patients with posterior interbody fusion; the average preoperative vertebral slippage was 46.9% (range: 25 - 75%) versus 14.6% (range: 15 - 25%) postoperatively. In patients with ITLIF, the average changes in economic and functional scores were 1.75 and 1.63 respectively. And the average preoperative vertebral slippage was 45.2% (range: 28 - 78%) compared with 26.3% (range: 14 - 28%) postoperatively. When two fusion techniques were compared, an overall superior reliability and resistance of systems was associated with the ITLIF procedure. But their clinical outcomes did not differ greatly (P > 0.05). CONCLUSIONS: The application of a segmental pedicle screw fixation is both feasible and efficacious.

Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages.

The dual-specificity phosphatase 6 (Dusp6) functions as a feedback regulator of fibroblast growth factor (FGF) signaling to limit the activity of extracellular signal-regulated kinases (ERKs) 1 and 2. We have identified a small-molecule inhibitor of Dusp6-(E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI)-using a transgenic zebrafish chemical screen. BCI treatment blocked Dusp6 activity and enhanced FGF target gene expression in zebrafish embryos. Docking simulations predicted an allosteric binding site for BCI within the phosphatase domain. In vitro studies supported a model in which BCI inhibits Dusp6 catalytic activation by ERK2 substrate binding. We used BCI treatment at varying developmental stages to uncover a temporal role for Dusp6 in restricting cardiac progenitors and controlling heart organ size. This study highlights the power of in vivo zebrafish chemical screens to identify new compounds targeting Dusp6, a component of the FGF signaling pathway that has eluded traditional high-throughput in vitro screens.

Inhibition of histone deacetylase expands the renal progenitor cell population.

One of the first hallmarks of kidney regeneration is the reactivation of genes normally required during organogenesis. Identification of chemicals with the potential to enhance this reactivation could therapeutically promote kidney regeneration. Here, we found that 4-(phenylthio)butanoic acid (PTBA) expanded the expression domains of molecular markers of kidney organogenesis in zebrafish. PTBA exhibits structural and functional similarity to the histone deacetylase (HDAC) inhibitors 4-phenylbutanoic acid and trichostatin A; treatment with these HDAC inhibitors also expanded the renal progenitor cell population. Analyses in vitro and in vivo confirmed that PTBA functions as an inhibitor of HDAC activity. Furthermore, PTBA-mediated renal progenitor cell expansion required retinoic acid signaling. In summary, these results support a mechanistic link among renal progenitor cells, HDAC, and the retinoid pathway. Whether PTBA holds promise as a therapeutic agent to promote renal regeneration requires further study.

[Treatment of upper cervical spine instability with posterior fusion plus atlantoaxial pedicle screw].

OBJECTIVE: To evaluate the clinical efficacies, indications and application values of posterior fusion plus pedicle screw fixation in the treatment of upper cervical spine instability. METHODS: From May 2006 to December 2010, a total of 24 patients with atlantoaxial instability were treated with C1-2 pedicle screws and rod fixation under general anesthesia. There were 18 males and 6 females with a mean age of 49.8 years old (range: 17 - 69). RESULTS: The postoperative radiographs verified a good position of all screws with satisfactory atlantoaxial reduction. A mean follow-up period of 23 months (range: 3 - 45) showed no injury of spinal cord and vertebral artery or inter fixation failure. Atlantoaxial alignment and stability were restored without instrumentation-related complications. CONCLUSION: Posterior atlantoaxial pedicle screw and rod fixation provide immediate three-dimensional rigid fixation of atlantoaxial joint. It is a more effective technique than with previously reported techniques.

Preliminary report of modified expansive laminoplasty in the treatment of thoracic ossification of the ligamentum flavum.

OBJECTIVE: This study was performed to evaluate the role of posterior suspension of the laminae-ossification of the ligamentum flavum complex combined with miniplate fixation (modified expansive thoracic laminoplasty) in treating thoracic ossification of the ligamentum flavum (TOLF). METHODS: Eight patients with TOLF treated by modified expansive thoracic laminoplasty were retrospectively analyzed. Their general information, operative time, intraoperative blood loss, and postoperative complications were recorded. Neurological functional recovery was evaluated by the modified Japanese Orthopaedic Association (mJOA) score and Hirabayashi recovery rate preoperatively, postoperatively, and at the final follow-up. Preoperative and postoperative imaging was performed, and the decompression range and internal fixation positioning were evaluated. RESULTS: The mJOA score significantly improved from 4.63 points preoperatively to 9.0 points at the final follow-up (Hirabayashi recovery rate of 77.75%). Postoperative computed tomography and magnetic resonance imaging revealed sufficient decompression of the surgical segment. At the final follow-up, the internal implants were well-placed, the lamina-ligamentum flavum complex showed no significant displacement, and neurological functional recovery was satisfactory. CONCLUSION: Surgical treatment of TOLF is complicated and high-risk. Characterized by simplicity and sufficient decompression, modified expansive thoracic laminoplasty can reduce the risk of cerebrospinal fluid leakage and nerve injury with satisfactory neurological functional recovery.

Investigation of Preoperative Traction Followed by Percutaneous Kyphoplasty Combined with Percutaneous Cement Discoplasty for the Treatment of Severe Thoracolumbar Osteoporotic Vertebral Compression Fractures.

OBJECTIVE: To evaluate the feasibility, clinical efficacy and imaging results of preoperative traction (PT) followed by percutaneous kyphoplasty (PKP) combined with percutaneous cement discoplasty (PCD) for treating severe thoracolumbar osteoporotic vertebral compression fractures (OVCFs). METHODS: A total of 13 patients with severe thoracolumbar OVCFs treated by PT followed by PKP combined with PCD were enrolled. General information, PT time, operation time, postoperative hospital stay, perioperative complications, visual analog scale (VAS) score, Oswestry disability index (ODI) score, local kyphosis angle, intervertebral angle (IVA), anterior vertebral height (AVH) and posterior vertebral height (PVH) were recorded. RESULTS: The average VAS score at admission was 7.4±3.5, decreased to 4.3±1.7 after PT and 2.3±0.7 three days after operation, and 1.5±0.9 at last follow-up. The average ODI score was 73.7±21.4 before operation, decreased to 26.6±9.3 three days after operation and 13.7±7.1 at last follow-up. Compared to VAS and ODI scores at admission, these at the third day after operation and last follow-up were significantly different. At admission, the IVA was 3.4°±6.8°, the disc height was 5.7±1.2mm, the AVH was 10.7±3.2mm, and the PVH was 25.7±4.2 mm, which, after PT, changed to 8.1°±7.3°, 8.6±2.6mm, 18.5±2.8mm, and 26.2±7.1mm, respectively, and the differences were significant. The average kyphotic angle was 43.4°±17.8° at admission, and decreased to 26.3°±6.7° after PT, 17.5°±8.4° three days after operation and 19.1°±10.3° at last follow-up, and the differences were significant. CONCLUSION: PT followed by PKP combined with PCD for the treatment of severe thoracolumbar OVCFs was an effective and simple procedure with satisfactory short-term clinical outcomes by relieving pain and improving kyphosis.

HDAC6 inactivates Runx2 promoter to block osteogenesis of bone marrow stromal cells in age-related bone loss of mice.

BACKGROUND: Senile osteoporosis can cause bone fragility and increased risk for fractures and has been one of the most prevalent and severe diseases affecting the elderly population worldwidely. The underlying mechanisms are currently intensive areas of investigation. In age-related bone loss, decreased bone formation overweighs increased bone resorption. The molecular mechanisms underlying defective bone formation in age-related bone loss are not completely understood. In particular, the specific role of histone acetylation in age-related bone loss has not been examined thoroughly. METHODS: We employed 6- and 18-month-old mice to investigate the mechanisms of defective bone formation in age-related bone loss. Bone marrow stromal cells (BMSCs) were induced to undergo in vitro osteogenic differentiation. Chromatin immunoprecipitation (ChIP) was used to investigate the binding of histone deacetylases (HDACs) on Runx2 promoter in BMSCs. Luciferase reporter and transient transfection assay were employed to study Runx2 gene expression modulation by HDAC and androgen receptor (AR). siRNA and HDAC6 inhibitor, Tubastatin A, were used to inhibit HDAC6 in vitro. And systemic administration of Tubastatin A was used to block HDAC6 in vivo. RESULTS: Age-related trabecular bone loss was observed in 18-month-old mice compared with 6-month-old mice. In vitro osteogenic differentiation potential of BMSCs from 18-month-old mice was weaker than 6-month-old mice, in which there was Runx2 expression inactivation in BMSCs of 18-month-old mice compared with 6-month-old mice, which was attributable to HDAC6-mediated histone hypoacetylation in Runx2 promoter. There was competitive binding of HDAC6 and AR on Runx2 promoter to modulate Runx2 expression in BMSCs. More importantly, through siRNA- or specific inhibitor-mediated HDAC6 inhibition, we could activate Runx2 expression, rescue in vitro osteogenesis potential of BMSCs, and alleviate in vivo age-related bone loss of mice. CONCLUSION: HDAC6 accumulation and histone hypoacetylation on Runx2 promoter contributed to the attenuation of in vitro osteogenic differentiation potential of BMSCs from aged mice. Through HDAC6 inhibition, we could activate Runx2 expression and osteogenic differentiation potential of BMSCs from aged mice and alleviate the age-related bone loss of aged mice. Our study will benefit not only for understanding the age-related bone loss, but also for finding new therapies to treat senile osteoporosis.

Synthesis of the parent and substituted tetracyclic ABCD ring cores of camptothecins via 1-(3-aryl-2-propynyl)- 1,6-dihydro-6-oxo-2-pyridinecarbonitriles.

A new synthetic pathway to the parent and substituted ABCD ring cores of the camptothecin family of alkaloids was developed. The N-alkylation of 1,6-dihydro-6-oxo-2-pyridinecarbonitrile (2) with 3-bromo-1-phenylpropyne provided 3a using Curran's protocol. Treatment of 3a with a catalytic amount of DBU (5 mol %) at 110 degrees C for 12 h produced indolizino[1,2-b]quinolin-9(11H)-one (6a), the parent ABCD ring core of camptothecin, in essentially quantitative yield.

[MEDIUM-TERM EFFECTIVENESS OF Waveflex SYSTEM IN TREATMENT OF MULTIPLE LUMBAR DEGENERATIVE DISEASES].

OBJECTIVE: To evaluate the medium-term effectiveness of Waveflex system in the treatment of multiple lumbar degenerative diseases. METHODS: Between May 2010 and July 2012, 26 patients with multiple lumbar degenerative diseases underwent posterior decompression, transforaminal lumbar interbody fusion (TLIF), and internal fixation with Waveflex system. There were 15 males and 11 females, aged 23-65 years (mean, 34.2 years). The disease duration was 9 months to 8 years (median, 3 years and 3 months). The lesion located at L3-S1. The visual analogue scale (VAS), Oswestry disability index (ODI), and the short-form 36 health survey scale (SF-36) were used to evaluate the status of clinical recovery, meanwhile the Stauffer-Coventry evaluation standard was used to access the satisfaction at last follow-up; the disc space height (DSH), intervertebral angle (IVA), and range of motion (ROM) were measured on X-ray film or three-dimensional CT, and the adjacent segment degeneration was classified by Pfirrmann score based on MRI findings. RESULTS: All patients obtained primary incision healing without nerve injury, cerebrospinal fluid leakage, or internal fixation failure. All patients were followed up 31-50 months (mean, 40.6 months). The VAS, ODI, and SF-36 scores were significantly improved at 6 months after operation and last follow-up when compared with preoperative ones (P<0.05), but no significant difference was found between at 6 months and last follow-up (P>0.05). According to the Stauffer-Coventry evaluation standard, the results were excellent in 21 cases, good in 2 cases, moderate in 2 cases, and poor in 1 case, with an excellent and good rate of 88.5% at last follow-up. X-ray films showed that there was no complication of screws pulling-out or fixed rod rupture and displacement. At 7 days, 6 months, and last follow-up, the DSH of adjacent segment was significantly increased (P<0.05), and the ROM of adjacent segment was significantly decreased (P<0.05) when compared with preoperative ones; there was no significant difference in IVA between at pre- and post-operation (P>0.05). According to Brantigan grade for fusion, 19 cases were rated as grade E, 6 cases as grade D, and 1 case as grade C, and the fusion rate was 96%. There was no significant difference in Pfirrmann score between at pre-operation and last follow-up (Z=0.000, P=1.000). CONCLUSION: The Waveflex system combined with TLIF is effective and safe to treat multiple lumbar degenerative diseases during medium-term follow-up.

Synthesis and structure of a helical diindenophenanthrene with four congested phenyl substituents as a molecular spiral staircase.

Treatment of 9 with potassium tert-butoxide produced 10 having a helical twist in a single operation. The X-ray structure of 10 shows that the four phenyl substituents are essentially parallel to one another but are virtually perpendicular to the helical axis of the diindenophenanthrene ring system. Viewing from the direction perpendicular to the helical axis, the structure of 10 resembles that of a segment of a spiral staircase having four parallel steps.

Treatment of upper cervical spine instability with posterior fusion plus atlantoaxial pedicle screw.

Clinical results of posterior fusion plus pedicle screw fixation in the treatment of upper cervical spine instability were taken under consideration. 24 patients with atlantoaxial instability were treated with C1-2 pedicle screws and rods fixation under general anesthesia. There were 18 males and 6 females with mean age of 49.8 years (age range 17-69 years). The postoperative radiographs verified good position of all screws, with satisfactory atlantoaxial reduction. Follow-up for 3-45 months (average 23 months) showed no spinal cord and vertebral artery injury or interfixation failure. Atlantoaxial alignment and stability were restored without complication due to instrumentation. In conclusion, posterior atlantoaxial pedicle screw and rod fixation provide immediate three-dimensional rigid fixation of atlantoaxial joint and are more effective techniques compared with previously reported techniques.

[Surgical treatment of postoperative deep wound infection after posterior lumbar interlumbar fusion of the lumbar stenosis].

OBJECTIVE: To study surgical treatment for the deep wound infections after the operation of posterior lumbar interlumbar fusion (PLIF) in lumbar spinal stenosis. METHODS: From December 2005 to December 2010,10 patients with the deep wound infection of the PLIF were analyzed retrospectively, including 4 males and 6 females, with a mean age of 52.8 years (ranged from 34 to 70 years). All the patients were treated with debridement and the drainage. The sensitive antibiotics were used. The VAS score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and JOA lumbar score were used to compare the clinical results pre-and post-operation. RESULTS: All the patients were followed up, and the mean duration was 24 months (ranged from 19 to 28 months). One patient developed to an intervertebral space infection and the cage was removed. One patient suffered a radical central nerve system infection and died after the debridement. Other 8 patients got a good clinical result. The VAS score decreased from preoperative 8.0 +/- 0.4 to postoperative 2.8 +/- 0.3; JOA score improved from preoperative 10.30 +/- 3.02 to postoperative 24.10 +/- 2.85; ESR decreased from preoperative (85.0 +/- 17.0) mm/h to postoperative (14.0 +/- 6.0) mm/h; both CRP and WBC decreased from preoperative (73.5 +/- 14.3) mg/L, (11.1 +/- 1.8) x 10(9)/L to postoperative (5.1 +/- 1.1) mg/L, (7.4 +/- 0.5) x 10(9)/L respectively. CONCLUSION: Treatment of patients with deep wound infections after PLIF with debridement, drainage, and sensitive antibiotics could get a good long-term clinical result, which is important to treat the patients with high-risk factors. Early diagnosis and operation is the key to deal with the patients with deep wound infections after PLIF.

[Comparison between bipedicular approach and uni-extrapedicular approach in application of vertebroplasty].

OBJECTIVE: To analyze the advantages and disadvantages of bipedicular approach and uni-extrapedicular approach of vertebroplasty in treating osteoporotic vertebral compression fractures (OVCFs). METHODS: From January 2008 to December 2010,53 patients with OVCFs were retrospectively analyzed. There were 24 males, 30 females with an average age of 66.9 years (ranged,59 to 88 years). Among them, 26 cases were treated with bipedicular approach, 28 cases were treated with uni-extrapedicular approach. The data of bone cement injection, radiology exposure times, operation time, bone cement leakage and vessels nerve complications were observed. Cobb angle, vertebral compression ration were observed by imaging data, and evaluate recovery of deformity. RESULTS: The data of bone cement injection, radiology exposure times, operation time, VAS score were (6.6 +/- 0.8) ml and (6.8 +/- 1.5) ml, (21.7 +/- 4.0) times and (17.9 +/- 3.6) times, (40.5 +/- 5.5) min and (31.6 +/- 9.1) min, (2.8 +/- 0.6) scores and (3.1 +/- 0.5) scores respectively. Cobb angle,vertebral compression ration were (7.6 +/- 2.0) degrees and (6.9 +/- 2.6) degrees, (18.1 +/- 5.8)% and (16.5 +/- 6.1)%. There were no vascular nerve complications occurred. For bone cement leakage, 3 cases (11%) in bipedicular approach and 3 cases (11%)in uni-extrapedicular approach. There was no significant differences between two groups in VAS score, recovery of vetebral body, Cobb angle, bone cement injection and bone cement leakage, but had significant differences in radiology exposure times and operation time (P<0.05). CONCLUSION: Both of two approaches can treat OVCFs well, especially extropedicle approach which could reduce operation time and radiation shoot frequency.