An "Iron-phagy" nanoparticle inducing irreversible mitochondrial damages for antitumor therapy.

Cellular iron is inseparably related with the proper functionalities of mitochondria for its potential to readily donate and accept electrons. Though promising, the available endeavors of iron chelation antitumor therapies have tended to be adjuvant therapies. Herein, we conceptualized and fabricated an "iron-phagy" nanoparticle (Dp44mT@HTH) capable of inducing the absolute devastation of mitochondria via inhibiting the autophagy-removal of impaired ones for promoting cancer cell death. The Dp44mT@HTH with hyaluronic acid (HA) as hydrophilic shell can specifically target the highly expressed CD44 receptors on the surface of 4T1 tumor cells. After internalization and lysosomal escape, the nanoparticle disassembles in response to the reactive oxygen species (ROS), subsequently releasing the iron chelator Dp44mT and autophagy-inhibitory drug hydroxychloroquine (HCQ). Dp44mT can then seize cellular Fe2+ to trigger mitochondrial dysfunction via respiratory chain disturbance, while HCQ not only lessens Fe2+ intake, but also impedes fusions of autophagosomes and lysosomes. Consequentially, Dp44mT@HTH induces irreversible mitochondrial impairments, in this respect creating a substantial toxic stack state that induces apoptosis and cell death. Initiating from the perspective of endogenous substances, this strategy illuminates the promise of iron depletion therapy via irreversible mitochondrial damage induction for anticancer treatment.

[Value of predicting preoperative risk in orthopedic surgery by using POSSUM].

OBJECTIVE: To assess the use of Physical and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) scoring system in predicting outcomes of patients undergoing orthopedic surgery and provide guidance for operation treatment decisions. METHODS: From April 2009 to September 2010, a total of 779 cases went operation in Beijing Hospital were collected.They were divided into two groups according to the presence or absence of complications.The patients' postoperative complications were predicted by POSSUM and compared to the actual morbidity to verify the effectiveness of the equation.Logistic regression was taken to make appropriate improvements for the POSSUM equation.ROC curve was drawn to describe the compliance of the original and new equations. RESULTS: In the 779 cases, the morbidity predicted by POSSUM is 212 cases while the actual morbidity is 65 cases.Of all risk factors, echocardiography ejection fraction showed a close relationship with postoperative complications (P<0.01). In the original equation, actual complication group compared with non-complication group, the difference was statistically significant (P<0.01). In the modified equation, complication group compared with non-complication group, the difference was statistically significant (P<0.01). Compared with the original one , the modified POSSUM had better predictive value on postoperative morbidity, and the comparison of AUC between the two groups was statistically significant ((0.67 ± 0.12) vs (0.75 ± 0.08), P<0.01). CONCLUSION: POSSUM over predicted morbidity of patients undergoing orthopedic surgery, it can be more accurate when modified appropriately.