ANXA2 and Rac1 negatively regulates autophagy and osteogenic differentiation in osteosarcoma cells to confer CDDP resistance.

BACKGROUND: Cisplatin (CDDP) is a mainstay chemotherapeutic agent for OS treatment, but drug resistance has become a hurdle to limit its clinical effect. Autophagy plays an important role in CDDP resistance in OS, and in the present study we explored the role of ANXA2 and Rac1 in dictating CDDP sensitivity in OS cells. METHODS: ANXA2 and Rac1 expression levels were examined by Western blot and autophagy induction was detected by transmission electron miscroscope (TEM) in the clinical samples and OS cell lines. CDDP resistant cells were established by exposing OS cells to increasing doses of CDDP. The effects of ANXA2 and Rac1 knockdown on CDDP sensitivity were evaluated in the cell and animal models. RESULTS: Reduced autophagy was associated with the increased expression of ANXA2 and Rac1 in CDDP resistant OS tumor samples and cells. Autophagy suppression promoted CDDP resistance and inducing autophagy re-sensitized the resistant cells to CDDP treatment in vitro and in vivo. Further, knocking down ANXA2 or Rac1 re-activated autophagy and attenuated CDDP resistance in OS cells. We further demonstrated that CDDP resistant OS cells displayed a poorer osteogenic differentiation state when compared to the parental cell lines, which was significantly reversed by autophagy re-activation and ANXA2 or Rac1 silencing. CONCLUSION: Our findings revealed a complicated interplay of ANXA2/Rac1, autophagy induction, and osteogenic differentiation in dictating CDDP resistance in OS cells, suggesting ANXA2 and Rac1 as promising targets to modulate autophagy and overcome CDDP resistance in OS cells.

Effect of early enteral nutrition in elderly patients with hip fracture during the perioperative period.

OBJECTIVE: This study aimed to assess the effects of early enteral nutrition (EN) in elderly patients with hip fracture. METHODS: The patients were classified into two groups (with and without EN). We compared the pre- and postoperative albumin (ALB) and inflammatory marker levels of each group and the time spent in bed and quality of life 3 months after surgery between the two groups. RESULTS: The pre- and postoperative IL-6 levels of the experimental group (61.68 ± 51.80 pg/L) were lower than those of the control group (233.11 ± 206.31 pg/L) (P< 0.001). The experimental group spent a shorter period of time in bed (38.75 ± 14.26 days) in comparison to the control group (99.71 ± 56.87 days) (P< 0.001). Quality of life was better in the experimental group than in the control group (P< 0.001). CONCLUSIONS: Early EN reduced the increment of postoperative IL-6 levels and improved healing postoperatively.

Restrictive blood transfusion strategies and associated infection in orthopedic patients: a meta-analysis of 8 randomized controlled trials.

This study sought to evaluate whether restrictive blood transfusion strategies are associated with a risk of infection in orthopedic patients by conducting a meta-analysis of randomized controlled trials (RCTs). RCTs with restrictive versus liberal red blood cell (RBC) transfusion strategies were identified by searching Medline, Embase, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from their inception to December 2014. Eight RCTs with infections as outcomes were included in the final analysis. According to the Jadad scale, all studies were considered to be of high quality. The pooled risk ratio [RR] for the association between transfusion strategy and infection was 0.65 (95% CI, 0.47-0.91; p = 0.012), and the number of patients needed to treat to avoid an infection using a restrictive transfusion strategy was 62. No heterogeneity was observed. The sensitivity analysis indicated unstable results, and no significant publication bias was observed. This meta-analysis of RCTs demonstrates that restrictive transfusion strategies in orthopedic patients result in a significant reduction in infections compared with more liberal strategies.

Opioids contribute to fracture risk: a meta-analysis of 8 cohort studies.

OBJECTIVE: To evaluate the association between chronic opioid use for non-cancer pain and fracture risk by conducting a meta-analysis of cohort studies. METHODS: Cohort studies were identified by searching PubMed and EMBASE from their inception to July 2014. A fracture was considered an endpoint. The information was extracted by two authors independently. When the heterogeneity was significant, a random-effects model was used to calculate the overall pooled risk estimates. RESULTS: Eight cohort studies were included in the final meta-analysis. On the basis of the Newcastle-Ottawa Scale (NOS), six studies were considered to be of high quality. The overall combined relative risk for the use of opioids and fractures was 1.88 (95% confidence interval [CI] 1.51-2.34). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed. CONCLUSIONS: This meta-analysis of cohort studies demonstrates that opioids significantly increase the risk of fractures.