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.

Immune checkpoint inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. To date, PD-1/PD-L1 inhibitors have been approved for the treatment of specific types of tumors and obtained good clinical efficacy. However, patients with osteosarcoma showed poor response to anti-PD-1/PD-L1 therapy, the mechanism of which is not well understood. In this study, we found that osteosarcoma tissues were heavily infiltrated by myeloid-derived suppressor cells (MDSCs) which could inhibit cytotoxicity T cell (CTL) expansion. Further study revealed that the vast majority of tumor-infiltrating MDSCs were CXCR4 positive and could migrate toward an SDF-1 gradient. The binding of SDF-1 to its receptor CXCR4 results in the activation of downstream AKT pathway that mediates reduced apoptosis of MDSCs. We also demonstrated that AMD3100, a CXCR4 antagonist, has a synergistic effect with anti-PD-1 antibody in tumor treatment in a murine model of osteosarcoma. These findings provide the basis for establishing CXCR4 antagonist and PD-1/PD-L1 inhibitors co-administration as a novel therapeutic regimen for patients with osteosarcoma and hold great promise for improving the therapeutic effect of osteosarcoma.

In the ageing skeleton, the balance of bone reconstruction could commonly be broken by the increasing of bone resorption and decreasing of bone formation. Consequently, the bone resorption gradually occupies a dominant status. During this imbalance process, osteoclast is unique cell linage act the bone resorptive biological activity, which is a highly differentiated ultimate cell derived from monocyte/macrophage. The erosive function of osteoclasts is that they have to adhere the bone matrix and migrate along it, in which adhesive cytoskeleton recombination of osteoclast is essential. In that, the podosome is a membrane binding microdomain organelle, based on dynamic actin, which forms a cytoskeleton superstructure connected with the plasma membrane. Otherwise, as the main adhesive protein, integrin regulates the formation of podosome and cytoskeleton, which collaborates with the various molecules including: c‐Cbl, p130^Cas, c‐Src and Pyk2, through several signalling cascades cross talking, including: M‐CSF and RANKL. In our current study, we discuss the role of integrin and associated molecules in osteoclastogenesis cytoskeletal, especially podosomes, regulation and relevant signalling cascades cross talking.

Percutaneous pedicle screw fixation (PPSF) has been a popular approach for treating thoracolumbar and lumbar fracture, and its relevant complications have been gradually recognized. This study aimed to summarize the complications of PPSF in treating thoracolumbar and lumbar fracture as well as the management and outcomes of the complications. We retrospectively analyzed the patients with thoracolumbar and lumbar fracture who were admitted to our department from February 2011 to February 2015 and underwent posterior PPSF. Information on demographics, medical comorbidities, radiographs, and treatment was obtained from hospital medical records and follow-up records. Main outcome indexes included adverse clinical and radiological outcomes during and after surgery. A total of 781 patients were included in this study. Forty-six patients (5.9%) presented with complications during or after surgery. The complications included intraoperative guide wire breakage, abdominal artery injury, spinal dura mater injury, postoperative pedicle screw misplacement, screw breakage, plug screw falling off, connecting rod loosening, poor reduction, and late infection. Among the 39 cases with postoperative complications, 14 underwent revision surgery, and the remaining patients underwent conservative treatment and presented good outcomes. PPSF is associated with the following complications: guide wire rupture, blood vessel injury, cerebrospinal fluid leakage, screw misplacement, poor reduction, failed internal fixation, and infection. A thorough preoperative evaluation, accurate operation, and timely and correct management of complications are critical to achieving satisfactory surgical outcomes.