Nano-hydroxyapatite modulates osteoblast lineage commitment by stimulation of DNA methylation and regulation of gene expression

Hydroxyapatite (HA) is the primary structural component of the skeleton and dentition. Under biological conditions, HA does not occur spontaneously and therefore must be actively synthesized by mineralizing cells such as osteoblasts. The mechanism(s) by which HA is actively synthesized by cells and deposited to create a mineralized matrix are not fully understood and the consequences of mineralization on cell function are even less well understood. HA can be chemically synthesized (HAp) and is therefore currently being investigated as a promising therapeutic biomaterial for use as a functional scaffold and implant coating for skeletal repair and dental applications. Here we investigated the biological effects of nano-HAp (10 × 100 nm) on the lineage commitment and differentiation of bone forming osteoblasts. Exposure of early stage differentiating osteoblasts resulted in dramatic and sustained changes in gene expression, both increased and decreased, whereas later stage osteoblasts were much less responsive. Analysis of the promoter region one of the most responsive genes, alkaline phosphatase, identified the stimulation of DNA methylation following cell exposure to nano-HAp. Collectively, the results reveal the novel epigenetic regulation of cell function by nano-HAp which has significant implication on lineage determination as well as identifying a novel potential therapeutic use of nanomaterials.     

正交试验优选牙周康胶囊的水提醇沉工艺

目的研究牙周康胶囊的水提醇沉工艺,优选最佳工艺。方法采用正交试验法,以干膏率和芍药苷含量为检测指标,考察4种因素(煎煮次数、加水量、煎煮时间、醇沉浓度)对工艺的影响。结果牙周康胶囊的最佳水提醇沉工艺为:加16倍水,每次煎煮1h,煎煮3次,醇沉浓度为40%。结论确定的提取方法适合于牙周康胶囊的制备。     

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.     

Early hypothermia as risk factor in severely burned patients: A retrospective outcome study

IntroductionBurn trauma-related hypothermia is a frequent observation but risk factors and impact on patient related outcome are ambiguously reported. It is expected that hypothermia is associated with increased mortality and reduced overall outcome in severely burned patients, but available evidence is limited.MethodsThis retrospective single-center-study reviewed preclinical service protocols and medical records of patients sustaining a burn with a total body surface area (TBSA) ≥15% from 2008 to 2012. General patient and burn specific characteristics, outcome parameters as well as body temperature at admission measured via urine catheter or nasal temperature probe were recorded and statistically analyzed comparing normothermic (≥36 °C), mild hypothermic (<36 °C) and severely hypothermic (<34.5 °C) patients. Chi-square test was performed to demonstrate impact of hypothermia on primary outcome parameters and to reveal risk factors for developing hypothermia. To assess independent influences on mortality, a multivariate logistic regression analysis was performed.ResultsOut of 300 patients matching inclusion criteria, a sufficient record of temperature was found in 144 patients (48%). Out of 141 eligible patients with an average burn extent (SD) of 33.38% (24.5%) TBSA, 31.9% (n = 45) suffered from severe hypothermia (<34.5 °C) and 28.4% (n = 40) showed mild hypothermia. Total burn extent, presence of full thickness burns, presence of inhalation injury, preclinical mechanical ventilation and administration of sedative drugs were risk factors for developing hypothermia. Patients’ age, total burn extent and presence of full thickness burns could be identified as independent factor for mortality. Although a trend towards an independent positive influence of normothermia at admission on mortality was seen, it was not statistically significant.ConclusionIncidental hypothermia of burned patients is associated with an increased mortality and needs to be addressed by emergency health care providers and immediately at the burn center. Especially patients with extensive burns, full-thickness burns, inhalation injury or patients undergoing preclinical intubation are at risk for hypothermia and benefit from any measures for temperature preserving.     

Please quote: Tian Y, Liu GE, Zhao WJ, Peng YY, Song SM, Li L. Review of Chinese Journal of Traumatology in the year 2018. Chin J Traumatol. 2019;22(1):21–23. doi:10.1016/j.cjtee.2019.01.001

Li Y, Li PY, Sun SJ, et al. Chinese Trauma Surgeon Association for management guidelines of vacuum sealing drainage application in abdominal surgeries-Update and systematic review. Chin J Traumatol. 2019;22(1):1–11. doi:10.1016/j.cjtee.2018.10.005     

Effects of ALA-PDT on the macrophages in wound healing and its related mechanisms in vivo and in vitro

BackgroundSeveral studies have suggested the effectiveness of photodynamic therapy (PDT) for wound healing. Macrophages are critical immune cells necessary for regulated inflammation during wound repair. However, the available information regarding the effects of PDT on macrophages during cutaneous wound healing remains insufficient. This study aimed to further investigate these aspects in vivo and in vitro.MethodsMouse full-thickness wound models were used as the study samples to investigate the therapeutic effects and mechanisms of 5-aminolevulinic acid (ALA) PDT. Wound healing rate, granulation tissue formation, local inflammation, M1/M2 macrophages differentiation, were measured at different time points treated by ALA-PDT. The polarization of macrophages induced by ALA-PDT was further evaluated in vitro using PCR and western blot analysis.ResultsALA-PDT could promote formation of granulation tissue, increase inflammatory infiltration and activate M1 macrophages in the early stage of injury. While, ALA-PDT could also facilitate absorption of granulation tissue, inhibit inflammatory infiltration and enhance M2 macrophages polarization in the later stage of wound repair. In vitro, ALA-PDT could modulate the ratio of M2 polarization to M1 polarization via NF-κB signaling pathway.ConclusionsALA-PDT topical application stimulates wound healing by regulating formation of granulation tissue, inflammatory process and M1/M2 macrophages differentiation. The study places a preliminary theoretical basis for topical ALA-PDT to be administered clinically in cutaneous wounds healing.