BackgroundThe aim of this study was to investigate the correlation between facet tropism and spinal degenerative diseases, such as degenerative lumbar spondylolisthesis, degenerative lumbar scoliosis, and lumbar disc herniation.MethodsThis study retrospectively analysed clinical data from the Department of Orthopaedics at The First Affiliated Hospital of Nanchang University. Ninety-two patients were diagnosed with lumbar spondylolisthesis, 64 patients with degenerative scoliosis, and 86 patients with lumbar disc herniation between 1 October 2014 and 1 October 2016. All patients were diagnosed using 3.0 T magnetic resonance imaging and underwent conservative or operative treatment. Facet tropism was defined as greater than a ten degree between the facet joint angles on both sides.ResultsFor L3-L4 degenerative lumbar spondylolisthesis, one out of six cases had tropism compared to seven out of the 86 controls (p = 0.474). At the L4-L5 level, 17/50 cases had tropism compared to 4/42 cases in the control group (p = 0.013). At the L5-S1 level, 18/36 cases had tropism compared to 7/56 controls (p = 0.000). For degenerative lumbar scoliosis at the L1-L5 level, 83/256 cases had tropism as compared to 36/256 controls (p = 0.000). For L3-L4 lumbar disc herniation two out of eight cases had tropism compared to 14/78 controls (p = 0.625). At the L4-L5 level, 19/44 cases had tropism compared to four out of 42 controls (p = 0.001). At the L5-S1 level, 24/34 cases had tropism compared to 10/52 controls (p = 0.000).ConclusionAt the L4–5 and L5-S1 levels, facet tropism is associated with degenerative spondylolisthesis. In the degenerative lumbar scoliosis group, the number of case with facet tropism was significantly higher than that of the control group. Facet tropism was associated with lumbar disc herniation at the L4–5 and L5-S1 levels. Overall, in these three lumbar degenerative diseases, facet tropism is a common phenomenon.Electronic supplementary materialThe online version of this article (10.1186/s12891-017-1849-x) contains supplementary material, which is available to authorized users.

Background and Objectives Belatacept is a first-in-class, selective co-stimulation blocker recently approved for the prophylaxis of organ rejection in adult kidney transplant recipients. The objective of this study was to report the pharmacokinetics, pharmacodynamics, and immunogenicity of belatacept. Methods The pharmacokinetics, pharmacodynamics (CD86 receptor occupancy), and immunogenicity of belatacept were studied in de novo adult kidney transplant recipients in phase II and III clinical studies.Results Following multiple doses of 5 or 10 mg/kg, the geometric mean (percentage coefficient of variation) maximum serum concentration and area under the serum concentration-time curve over one dosing interval of belatacept were 136 (20 %) and 238 (27 %) lg/mL, and 13,587 (27 %) and 21,241 (35 %) lgÁh/mL, respectively. The median belatacept elimination half-life was 8-9 days. Belatacept exhibited concentration-dependent binding to CD86 receptors. The pre-dose CD86 receptor occupancy by belatacept decreased from 94 to 65 % between day 5 and 1 year post-transplant, with corresponding pre-dose trough serum concentrations of belatacept decreasing from *35 to 4 lg/mL during this period. The cumulative incidence of developing anti-belatacept antibodies was 5.3 % up to 3 years post-transplant and had no impact on belatacept exposure.Conclusions Belatacept in adult kidney transplant demonstrated linear pharmacokinetics with low variability, concentration-dependent pharmacodynamics, and a low incidence of anti-drug antibodies.

MicroRNAs play an important role in the development and progression of Ewing's sarcoma (ES). Especially, the expression of let-7a has been reported to be significantly downregulated in various cancers, and can affect the initiation and maintenance of tumor progression. However, the relative effects of let-7a on ES cells and relative mechanisms are largely unknown. In this study, we identified the underexpression of let-7a in human ES cells comparing with the human mesenchymal stem cells. Then, we sought to compensate for its loss through exogenous transfection with let-7a mimic into ES cell lines A673 and SK-ES-1. Restored let-7a expression inhibited cell proliferation, migration, as well as invasion; arrested cell cycle progression; and induced cell apoptosis of both cell lines. Moreover, bioinformatic prediction suggested that cyclin-dependent kinase 6 (CDK6), which is overexpressed and functions as an oncoprotein in ES cells, is a putative target gene of let-7a. Using mRNA and protein expression analysis and luciferase assays, we further identified the target role of CDK6. Finally, we found that restored CDK6 expression in ES cells that had been treated with let-7a mimic before could partly dampen let-7a-mediated tumor suppression. Taken together, our results showed that let-7a acted as a tumor suppressor in ES by targeting CDK6, and it may provide novel diagnostic and therapeutic options for human Ewing sarcoma clinical operation in future.

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Rationale:Schwannomas grow slowly, originating from the Schwann cells of the nerve sheath. Schwannomas of cranial origin have the highest incidence, followed by intraspinal schwannomas. However, paravertebral schwannoma is rare, and to our knowledge, giant paravertebral schwannomas near the lumbar nerve roots with bone destruction are extremely rare.Patient concerns:A 47-year-old Chinese woman complained of lower back soreness and a sensation of a bulging lumbar disc with no obvious cause for the past 3 years.Diagnosis:Lumbar magnetic resonance imaging showed a large mass with uneven density, 17 × 12 × 15 cm in size, located to the right of the 4th lumbar with obvious bony destruction. Histopathology and immunohistochemistry confirmed that this mass was a benign schwannoma.Interventions:Complete resection of the tumor (measuring about 17 × 12 × 15 cm in size) and vertebral reconstruction using internal fixation were performed.Outcomes:The patient was discharged without complications after surgery. The 3-year follow-up revealed that the patient recovered well with no evidence of recurrence.Lessons:Here, we emphasize the importance of careful radiological examination and reflect on the difficulty of tumor resection. Furthermore, understanding the treatment and diagnosis of lumbar paravertebral schwannoma is critical for plastic surgeons and radiologists when encountering similar cases.

Mouse model is an appropriate tool for pathogenic determination and study of host defenses during the fungal infection. Here, we established a mouse model of candidiasis with concurrent oral and vaginal mucosal infection. Two C. albicans strains sourced from clinical candidemia (SC5314) and mucosal infection (ATCC62342) were tested in ICR mice. The different combinational panels covering estrogen and immunosuppressive agents, cortisone, prednisolone and cyclophosphamide were used for concurrent oral and vaginal candidiasis establishment. Prednisolone in combination with estrogen proved an optimal mode for concurrent mucosal infection establishment. The model maintained for 1 week with fungal burden reached at least 10(5) cfu/g of tissue. This mouse model was evaluated by in vivo pharmacodynamics of fluconazole and host mucosal immunity of IL-17 and IL-23. Mice infected by SC5314 were cured by fluconazole. An increase in IL-23 in both oral and vaginal homogenates was observed after infection, while IL-17 only had a prominent elevation in oral tissue. This model could properly mimic complicated clinical conditions and provides a valuable means for antifungal assay in vivo and may also provide a useful method for the evaluation of host-fungal interactions.

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