Dingjun Hao

Long Noncoding RNA CRNDE Promotes Multiple Myeloma Cell Growth by Suppressing miR-451

It has been determined that long noncoding RNAs (lncRNAs) are identified as a potential regulatory factor in multiple tumors as well as multiple myeloma (MM). However, the role of colorectal neoplasia differentially expressed (CRNDE) in the pathogenesis of MM remains unclear. In this study, we found that the CRNDE expression level, in MM samples and cell lines, is higher than that in the control detected by real-time qPCR, which is also closely related to tumor progression and poor survival in MM patients. Knockdown of CRNDE significantly inhibits the proliferative vitality of MM cells (U266 and RPMI-8226), induces cell cycle arrest in the G0/G1 phase, and promotes apoptosis. After being transfected with siRNA, miR-451 expression observably increases. Bioinformatics analysis and luciferase assay reveal the interaction by complementary bonding between CRNDE and miR-451. Pearsons correlation shows that CRNDE is negatively correlated to miR-451 expression in human MM samples. Subsequently, miR-451 inhibitor rescues the inhibited tumorigenesis induced by CRNDE knockdown. Our study illustrates that lncRNA CRNDE induces the proliferation and antiapoptosis capability of MM by acting as a ceRNA or molecular sponge via negatively targeting miR-451, which could act as a novel diagnostic marker and therapeutic target for MM.

Posterior atlantoaxial fixation: a review of all techniques

BACKGROUND CONTEXT Posterior atlantoaxial fixation is an effective treatment for atlantoaxial instability. Great advancements on posterior atlantoaxial fixation techniques have been made in the past decades. However, there is no article reviewing all the posterior atlantoaxial fixation techniques yet. PURPOSE The aim was to review the evolution and advancements of posterior atlantoaxial fixation. STUDY DESIGN This was a literature review. METHODS The application of all posterior fixation techniques in atlantoaxial stabilization, including wiring techniques, interlaminar clamp fixation, transarticular fixation, screw-plate systems, screw-rod systems, and hook-screw systems, are reviewed and discussed. Recent advancements on the novel technique of atlantoaxial fixation are described. The combination of the C1 and C2 screws in screw-rod systems are described in detail. RESULTS All fixation techniques are useful. The screw-rod system appears to be the most popular approach. However, many novel or modified fixation methods have been introduced in recent years. CONCLUSIONS Great advancements on posterior atlantoaxial fixation techniques have been made in the past decades. The wiring technique and interlaminar clamps technique have fallen out of favor because of the development of newer and superior fixation techniques. The C1-C2 transarticular screw technique may remain the gold standard for atlantoaxial fusion, whereas screw-rod systems, especially the C1 pedicle screw combined with C2 pedicle/pars screw fixation, have become the most popular fixation techniques. Hook-screw systems are alternatives for atlantoaxial fixation.

The Efficiency of Zero-profile Implant in Anterior Cervical Discectomy Fusion: A Prospective Controlled Long-term Follow-up Study.

Study Design: A prospective controlled study. Objective: The aim of this study was to compare the safety and efficacy of the zero-profile device with that of an anterior cervical plate and cage in patients undergoing anterior cervical discectomy and fusion (ACDF). Summary of Background Data: A series of studies have indicated that anterior instruments produce good clinical results during ACDF. However, common implants are associated with a high rate of postoperative complications. A cervical stand-alone cage with integrated fixation for zero-profile segmental stabilization has been developed to solve this problem. Materials and Methods: A total of 46 patients with cervical radiculopathy or myelopathy were randomly treated with an anterior plate and a cage or a new zero-profile implant between September 2009 and April 2010. Patients were followed for 2 years. The operation time, blood loss, exposure to radiation, the Japan Department of Orthopedics Association (JOA) score, pain Visual Analogue Score (VAS), and dysphagia score were recorded. Results: The operation was completed successfully in 46 patients. Twenty-three patients received an anterior plate and cage (control group) and 23 patients received the new zero-profile implant (test group). Analysis of postoperative data at all protocol-defined intervals demonstrated improvement in all clinical outcomes for both the groups when compared with the corresponding preoperative data. No significant difference in VAS and JOA score was found in the 2 treatment groups. The test group had a greater reduction in dysphagia at all follow-up intervals, compared with the control group. No adjacent segment degeneration was found in the test group, whereas 4 patients in the control group developed degeneration in adjacent segments (P=0.045). Both the groups had no adverse events associated with the implant or implant surgery. Conclusions: The Zero-P implant is a viable alternative to ACDF in patients with persistently symptomatic, single-level cervical disk disease. The procedure requires more technical requirements than traditional plates.

The difference in superior adjacent segment pathology after lumbar posterolateral fusion by using 2 different pedicle screw insertion techniques in 9-year minimum follow-up.

Study Design. A prospective study was performed. Objective. To test the hypothesis that different pedicle screw insertion positions would increase the likelihood of superior adjacent segment degeneration (ASD). Summary of Background Data. Lumbar fusion surgery is a widely accepted treatment of lumbar diseases, such as lumbar stenosis, trauma, tumor, and spondylolisthesis. Fusion and clinical success rates have increased because of improvements in instrumentation and bone graft material. In contrast, numerous complications and problems of fusion surgery have been reported, with ASD being one of the most important. Methods. This prospective study included 210 patients with low-grade isthmic spondylolisthesis. From January 1999 to December 2003, patients were randomized underwent posterolateral fusion using 2 different pedicle screw insertion positions. The patients were followed up postoperatively and were assessed with regard to radiological and clinical outcomes. Radiological outcomes were assessed mainly on the basis of disc degeneration, facet joint degeneration, and bone fusion. Clinical outcomes were evaluated mainly with the use of visual analogue scale for pain and the Oswestry Disability Index. Results. A total of 178 of 210 (84.7%) patients were available for at least 9-year radiological and clinical follow-up data: 85.3% (87/102) patients in group A and 84.3% (91/108) patients in group B. Bone fusion was achieved in all patients at the last follow-up. ASD was proven in 110 (61.8%) of 178 patients. The incidences of radiographical and symptomatic ASD were 57.9% (103/178) and 3.9% (7/178), respectively. The incidence of ASD in group B was significantly lower than that in group A. Results of clinical outcomes showed lower visual analogue scale and Oswestry Disability Index scores in 2 groups than preoperative scores, but group B had greater improvement on the Oswestry Disability Index scores than group A in patients with ASD. Conclusion. The degeneration of superior adjacent segment is closely related to the position of the pedicle screws during lumbar fusion surgery. The position of the pedicle screw farther from the facet joint surface can reduce the degeneration of superior adjacent segment. Level of Evidence: 3

C2 Nerve Dysfunction Associated with C1 Lateral Mass Screw Fixation

The C1 lateral mass screw technique is widely used for atlantoaxial fixation. However, C2 nerve dysfunction may occur as a complication of this procedure, compromising the quality of life of affected patients. This is a review of the topic of C2 nerve dysfunction associated with C1 lateral mass screw fixation and related research developments. The C2 nerve root is located in the space bordered superiorly by the posterior arch of C1, inferiorly by the C2 lamina, anteriorly by the lateral atlantoaxial joint capsule, and posteriorly by the anterior edge of the ligamentum flavum. Some surgeons suggest cutting the C2 nerve root during C1 lateral mass screw placement, whereas others prefer to preserve it. The incidence, clinical manifestations, causes, management, and prevention of C2 nerve dysfunction associated with C1 lateral mass screw fixation are reviewed. Sacrifice of the C2 nerve root carries a high risk of postoperative numbness, whereas postoperative nerve dysfunction can occur when it has been preserved. Many surgeons have been working hard on minimizing the risk of postoperative C2 nerve dysfunction associated with C1 lateral mass screw fixation.

A Comparison Between Unilateral Transverse Process-pedicle and Bilateral Puncture Techniques in Percutaneous Kyphoplasty

Study Design. A prospective comparative study. Objective. To assess the clinical and radiological outcomes for the treatment of osteoporotic vertebral compression fractures using unilateral transverse process-pedicle and bilateral percutaneous kyphoplasty (PKP). Summary of Background Data. PKP is a widely used vertebral augmentation procedure for treating painful vertebral compression fractures. A percutaneous bilateral approach is typically used to access the vertebral body. Many previous studies have reported excellent clinical results with PKP. In contrast, numerous complications and problems have also been reported, such as puncture difficulty, cement leakage, and adjacent vertebral fracture. Methods. This prospective study included 316 patients with single-level lumbar osteoporotic vertebral compression fracture, 224 females and 92 males with a mean age of 71.5 years. Randomized patients underwent PKP using 2 different puncture techniques. The patients were followed up postoperatively and were assessed mainly with regard to clinical and radiological outcomes. Clinical outcomes were evaluated mainly using the visual analogue scale for pain and 36-Item Short Form Health Survey (SF-36) questionnaire for health status. Radiological outcomes were assessed mainly on the basis of radiation dose, bone cement distribution, vertebral body height, and kyphotic angle. Results. Patients were followed up from 12 to 28 months, with an average of 16.8 months. One hundred fifty-eight patients were treated with unilateral method and 151 patients were treated with bilateral method. In the unilateral group, the volume of the injected cement and radiation dose were significantly less than that in the bilateral group. All patients in both groups had significantly less pain after the procedures, compared with their preoperative period pain. No statistically significant differences were observed when visual analogue scale and 36-Item Short Form Health Survey were compared between the groups. Both unilateral and bilateral groups showed insignificant decrease in the kyphotic angle during the follow-ups. The kyphotic angle in the unilateral group improved more significantly than in the bilateral group. In the bilateral group, 16 patients had obvious pain in the puncture sites at 1 month postoperatively caused by facet joint violation. With local block treatment, the pain disappeared in all patients at the last follow-up. Conclusion. Both bilateral and unilateral PKP are relatively safe and provide effective treatment for patients with painful osteoporotic vertebral compression fracture. However, unilateral PKP received less radiation dose and operation time, it also offered a higher degree of deformity correction and resulted in less complication than bilateral PKP. Level of Evidence: 3

Psoralidin suppresses osteoclastogenesis in BMMs and attenuates LPS-mediated osteolysis by inhibiting inflammatory cytokines

Abstract Psoralidin is a metabolic product from the seed of psoraleacorylifolia, possessed anti‐inflammatory and immunomodulatory effects. We speculated that psoralidin might impact osteoclastogenesis and bone loss. By using both in vitro and in vivo studies, we observed psoralidin strongly inhibited RANKL induced osteoclast formation during preosteoclast cultures, suggesting that it acts on osteoclast precursors to inhibit RANKL/RANK signaling. At the molecular level, by using MAPKs specific inhibitors (U‐0126, SB‐203580 and SP‐600125) we demonstrated that psoralidin markedly abrogated the phosphorylation of p38, ERK, JNK. Moreover, the RANKL induced NF‐&kgr;B/p65 phosphorylation and I‐&kgr;B degradation were significantly inhibited by psoralidin. Further, psoralidin significantly suppressed osteoclastogenesis marker genes of TRAP, Cathepsin K and OSCAR. These were accompanied by the decreased expression of c‐Fos and NFATc1 transcription factors. Consistent with in vitro results, our in vivo and serologic studies showed psoralidin inhibited lipopolysaccharide induced bone resorption by suppressing the inflammatory cytokines: TNF‐&agr; and IL‐6 expression, as well as the ratio of RNAKL: OPG. These results collectively suggested that psoralidin could represent a novel therapeutic strategy for osteoclast‐related disorders, such as rheumatoid arthritis and postmenopausal osteoporosis. HighlightsPsoralidin suppress RANKL‐induced osteoclast formation, bone resorption, and F‐actin ring formation.Psoralidin inhibit RANKL‐mediated MAPKs and NF‐&kgr;B signaling pathway.Psoralidin decrease the expression of osteoclastogenesis marker genes and transcription factors.Psoralidin can suppress LPS‐induced osteoporosis in a mouse model.

Posterior Approach in Treating Sacral Fracture Combined With Lumbopelvic Dissociation

Type III Denis fracture of the sacrum is rare clinically, constituting approximately 16% of all sacral fractures. Because it is often complicated with neurologic injuries, treatment is crucial and difficult. Several surgical options are available for the treatment of type III Denis sacral fracture with lumbopelvic dissociation. The authors report 21 patients admitted to the hospital from February 2002 to May 2012 who had type III Denis sacral fracture combined with lumbopelvic dissociation. All of the patients were treated with posterior sacral lamina decompression, sacral nerve root decompression, fracture reduction, an integrated lumbopelvic internal fixation system, and posterolateral fusion. The authors recorded pre- and postoperative complications, fracture reduction, bone graft healing, and improvements in neurologic function, according to the Gibbons grading standard. The average surgical time was 190 minutes (range, 170-210), and the average amount of intraoperative bleeding was 960 mL (range, 930-1500). No intraoperative complications occurred. Twelve patients had complete recovery of neurologic function; 5 patients showed great improvement except for foot drop and impaired lower limb sensation; and 4 patients showed no improvement in lower limb, bladder, and rectum function. Gibbons grade decreased from an average of 3.43±0.51 before surgery to 1.76±1.09 at the last follow-up. Deep infections were noted in 2 cases, and in 1 case, vertebral screw loosening was observed 1 year postoperatively. Surgical reduction with lumbopelvic fixation is an ideal method for treating type III Denis sacral fracture with neurologic injury and lumbopelvic dissociation.

Diversity analysis of gut microbiota in osteoporosis and osteopenia patients

Some evidence suggests that bone health can be regulated by gut microbiota. To better understand this, we performed 16S ribosomal RNA sequencing to analyze the intestinal microbial diversity in primary osteoporosis (OP) patients, osteopenia (ON) patients and normal controls (NC). We observed an inverse correlation between the number of bacterial taxa and the value of bone mineral density. The diversity estimators in the OP and ON groups were increased compared with those in the NC group. Beta diversity analyses based on hierarchical clustering and principal coordinate analysis (PCoA) could discriminate the NC samples from OP and ON samples. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria constituted the four dominant phyla in all samples. Proportion of Firmicutes was significantly higher and Bacteroidetes was significantly lower in OP samples than that in NC samples (p < 0.05), Gemmatimonadetes and Chloroflexi were significantly different between OP and NC group as well as between ON and NC group (p < 0.01). A total of 21 genera with proportions above 1% were detected and Bacteroides accounted for the largest proportion in all samples. The Blautia, Parabacteroides and Ruminococcaceae genera differed significantly between the OP and NC group (p < 0.05). Linear discriminant analysis (LDA) results showed one phylum community and seven phylum communities were enriched in ON and OP, respectively. Thirty-five genus communities, five genus communities and two genus communities were enriched in OP, ON and NC, respectively. The results of this study indicate that gut microbiota may be a critical factor in osteoporosis development, which can further help us search for novel biomarkers of gut microbiota in OP and understand the interaction between gut microbiota and bone health.

Prospective, Self-controlled, Comparative Study of Transposterior Arch Lateral Mass Screw Fixation and Lateral Mass Screw Fixation of the Atlas in the Treatment of Atlantoaxial Instability.

Study Design: A prospective self-controlled study. Objective: The aim of the present study was to compare the application and clinical outcomes of transposterior arch lateral mass screw and lateral mass screw fixation of the atlas in the treatment of atlantoaxial instability. Summary of Background Data: Atlas posterior screw fixation techniques comprise transposterior arch lateral mass screw fixation and lateral mass screw fixation. Previous studies have focused mainly on the feasibility of the anatomy and the biomechanics of the methods. Methods: From June 2006 to February 2011, 66 patients with atlantoaxial instability were randomly assigned for treatment with transposterior arch lateral mass screw or lateral mass screw fixation of the atlas, combined with axis pedicle screw fixation. Patients were followed up regularly. The operation time, blood loss, intraoperative complications, Japan Department of Orthopedics Association Score, visual analog scale score, and bone fusion rates were recorded. Results: The operation was successful in all 66 cases, with all patients showing improvement in clinical symptoms. There were significant differences in operation time and blood loss between the 2 groups (P<0.001). The mean follow-up time was 49 months. At the final follow-up, the Japan Department of Orthopedics Association score was significantly better than the preoperative score (mean, 13.5; P<0.05). The mean postoperative improvement rate was 88.2% and the mean visual analog scale score was 1.9; both results were significant as compared with preoperative results (P<0.05). Bone fusion was achieved within 6 months after operation. No screw loosening, shifting, breakage, or atlantoaxial instability was observed. Six patients with atlas lateral mass screw placement had burst bleeding of C1–C2 venous plexus during surgery. Five patients had immediate pain and numbness at the occipitocervical region. Conclusions: Atlas transposterior arch lateral mass screw fixation is less invasive, simple, has fewer complications, and offers good fixation results for atlantoaxial instability as compared with lateral mass screw fixation.