Subcellular co-delivery of two different site-oriented payloads based on multistage targeted polymeric nanoparticles for enhanced cancer therapy.

The co-delivery of two or more anti-tumor agents using nanocarriers has shown great promise in cancer therapy, but more work is needed to selectively target drugs to specific subcellular organelles. To this end, our research has reported on "smart" polymeric nanoparticles that can encapsulate two different site-oriented pro-drug molecules, allowing them to reach their targeted subcellular organelles based on NIR-mediated controlled release, allowing for targeted modifications in the nucleus or the mitochondria. Specially, an all-trans retinoic acid (RA) conjugated cisplatin derivative (RA-Pt) can be delivered with high affinity to the nucleus of target cells, facilitating the binding of cisplatin to double-stranded DNA. Similarly, a synthesized derivative generated by conjugation of triphenylphosphine (TPP) and celastrol (TPP-Cet) may facilitate mitochondrial targeted drug delivery in tumor cells, inducing ROS accumulation and thereby leading to apoptosis. Relative to nanoparticles loaded with a single therapeutic agent, dual antitumor agent-loaded nanocarriers showed promising synergy, exhibiting significant tumor inhibition in vivo (81.5%), and less systemic toxicity than the free therapeutic agents alone or the drug-loaded nanoparticles without targeted ligands. These results indicated that site-oriented payloads can effectively enhance antitumor therapeutic efficiency and these studies offer a novel "multistage targeted-delivery" strategy in synergistic therapy for cancer treatment.

[Observation on therapeutic effect of acupoint catgut-embedding combined western medicine for epilepsy of generalized seizures type].

OBJECTIVE: To compare the efficacy differences between acupoint catgut-embedding combined western medicine (ACCWM) and simple western medicine (WM) for treatment of epilepsy of generalized seizures type. METHODS: Fifty-two patients with epilepsy of generalized seizures type were randomly divided into an ACCWM group (n=30) and a WM group (n=22). Dazhui (GV 14), Yaoshu (GV 2), Jiuwei (CV 15), Qihai (CV 6) were selected in the ACCWM group as the main acupoints combined with routine antiepileptic drugs, Valpromide was taken orally, 2.0 g/d for adult, 50 mg/kg x d for child. The WM group was treated with routine antiepileptic drugs. The epilepsy score and the attack frequency one year before the treatment and one year during treatment were observed and the therapeutic effects in the two groups were compared. RESULTS: The epilepsy score and the attack frequency were both decreased in the two groups (P<0.01, P<0.05), and the epilepsy score in the ACCWM group decreased significantly (6.57 +/- 3.29 vs 10.73 +/- 2.54, P<0.05). The total effective rate of 90.0% (27/30) in the ACCWM group was superior to that of 68.2% (15/22) in the WM group (P<0.05). CONCLUSION: The therapeutic effect of ACCWM is superior to that of simple western medicine in treating epilepsy of generalized seizures type. It can improve significantly the attack symptoms so as to enhance life quality of the patients with epilepsy.

Clinical effects of applying a tourniquet in total knee arthroplasty on blood loss.

BACKGROUND: Tourniquets used during total knee arthroplasty may lead to many complications. The aim of this study was to determine perioperative blood loss and its clinical relevance in total knee replacement surgery after applying a tourniquet. METHODS: From June 2009 to October 2009, 60 consecutive patients who underwent routine total knee arthroplasty were randomly divided into two groups and were treated with or without a tourniquet (30 patients/group). There were no significant differences in patient baseline characteristics between the two groups. We compared the two groups of patients in terms of intra- and postoperative bleeding, invisible or visible bleeding, and total blood loss. RESULTS: None of the patients showed poor wound healing, lower extremity deep venous thrombosis or other complications. The amount of blood loss during surgery was lower in the tourniquet group than in the control group (P < 0.01). However, postoperative visible bleeding (P < 0.05) and occult bleeding (P < 0.05) were significantly greater in the tourniquet group than in the control group. There was no significant difference in the total amount of blood loss between the two groups (P > 0.05). CONCLUSIONS: Tourniquet can reduce bleeding during total knee replacement surgery, but is associated with greater visible and invisible blood loss.