Macrophages play a crucial role in inflammatory-mediated bone loss. Orthodontic tooth movement (OTM) is associated with inflammatory bone remodeling. However, whether and how macrophages contribute to mechanical force-induced OTM remains unknown. In this study, we hypothesized that polarization of M1-like macrophages may contribute to the OTM. Orthodontic nickel-titanium springs were applied to the upper first molars of rats or mice to induce OTM. The distance of OTM gradually increased after mechanical force was applied to the rats for 5 and 10 d. M1-like macrophage polarization and expression of M1 cytokine tumor necrosis factor (TNF)-α also increased after force application. More importantly, monocyte/macrophage depletion in mice by injection of clodronate liposomes decreased the distance of OTM and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68(+) macrophages, accompanied by reduced expressions of M1 markers TNF-α and inducible nitric oxide synthase (iNOS), whereas systemic transfusion of M1 macrophages in mice increased them. Further experiments showed that injection of recombinant TNF-α increased the distance of OTM and the number of TRAP-positive osteoclasts and CD68(+) macrophages, as well as upregulated the expression of TNF-α and iNOS. Blockage of TNF-α by etanercept injection reduced the distance of OTM and the number of TRAP-positive osteoclasts and CD68(+) macrophages, as well as decreased the levels of TNF-α and iNOS. These data suggest that M1-like macrophage polarization promotes alveolar bone resorption and consequent OTM after mechanical force application.

SUMMARYWhat is known and objective: To perform a meta-analysis exploring the optimal single-dose regimen for managing tumour lysis syndrome (TLS) in children and adults with haematological malignancies. Methods: We systematically searched PubMed, MEDLINE, Web of Science, the Cochrane Library and the ClinicalTrials.gov website for studies regarding single-dose rasburicase in paediatric and adult patients with TLS. Data were analysed using Open MetaAnalyst statistical software. Results: Fifteen adult studies (fourteen retrospective studies and one randomized controlled trial) and four observational studies using children were extracted, with a total of 906 and 92 subjects, respectively. Single doses of 1Á5, 3, 4Á5, 6, 7Á5 mg and weight-based single doses of 0Á05 and 0Á15 mg/kg were compared. The response rate for 6, 7Á5 mg and 0Á15 mg/kg single doses was 90% (95% CI: 0Á825-0Á974), 98Á6% (95% CI: 0Á957-1Á015) and 93Á6% (95% CI: 0Á864-1Á007), respectively, and higher than other dosing regimens tested. The single doses of 6 mg and 0Á15 mg/kg rasburicase decreased uric acid levels more than the other regimens, and the mean uric acid reduction was 8Á45 mg/dL (95% CI, 7Á51-9Á38) and 10 mg/dL (95% CI, 8Á58-11Á42), respectively. What is new and conclusion: Our meta-analysis revealed that, for adult patients, a single 6 mg rasburicase dose is sufficient to normalize and sustain lower uric acid and creatinine levels in adults with TLS. This dose, therefore, balances cost and efficacy of treatment. The 3-and 4Á5-mg single dose can be considered if the baseline uric acid level <12 mg/dL, with close monitoring of clinical and biochemical parameters, and repeat dosing if required. The 1Á5 mg and 0Á15 mg/kg single dose were sufficient to manage TLS in children. WHAT IS KNOWN AND OBJECTIVETumour lysis syndrome (TLS) is a frequently encountered and lifethreatening oncologic emergency. It is characterized by severe electrolyte and metabolite abnormalities caused by rapid and massive breakdown of cancer cells and release of intracellular content into the systemic circulation, which leads to severe complications, such as hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcaemia.1,2 TLS occurs most commonly within 12-72 h after initiation of cytoreductive chemotherapy of haematological malignancies, especially in non-Hodgkin lymphoma and acute lymphocytic leukaemia (ALL), as well as in solid tumours that are characterized by high sensitivity to cytotoxic treatment, high proliferative rate or large tumour size or burden; however, it can also occur spontaneously without chemotherapy. 2-4Numerous studies have demonstrated that rasburicase is effective and safe in reducing uric acid (UA) levels and works within 4 h post-administration. [5][6][7][8] Rasburicase was approved by the US FDA for the treatment and prophylaxis of hyperuricemia in paediatric and adult patients with leukaemia, lymphoma or solid tumours who are receiving chemotherapy or at high risk of TLS, in 2002 and 2009, respectively. The recommended dose by the FDA i...

Independently or combined with APOE, LRP5 polymorphisms may lead to dyslipidemia and are associated with generalized aggressive periodontitis. Dyslipidemia may be a risk indicator for generalized aggressive periodontitis in the Chinese population. Furthermore, two LRP5 polymorphisms (rs682429 and rs312016) might be useful for identifying subjects at higher risk of generalized aggressive periodontitis.