Microenvironment-Triggered Degradable Hydrogel for Imaging Diagnosis and Combined Treatment of Intraocular Choroidal Melanoma.

Human choroidal melanoma (HCM) is one of the most common primary intraocular tumors and easily provokes liver metastases owing to the lack of sensitive and noninvasive therapeutic methods. Concerning the imaging diagnostics and therapeutic predicaments for choroidal melanoma, we designed microenvironment-triggered degradable hydrogels (RENP-ICG@PNIPAM:Dox-FA) based on ultrasmall (<5 nm) rare-earth nanoparticles (RENPs) with enhanced NIR-II luminescence. The ultrasmall diameter can significantly enhance the NIR-II luminescence performance of RENPs. RENPs were encapsulated by a dual-response PNIPAM hydrogel, which could release drug by responding to heat energy and glutathione under the tumor microenvironment. The in vitro/in vivo NIR-II imaging detection and antitumor activity were also compared systematically after different treatment conditions on ocular choroidal melanoma-1 cells and tumor-bearing mice, respectively. Besides, the degradability of the hydrogel composites under physiological conditions could be conducive to enhance the photothermal-chemotherapeutic effect and alleviate long-term biological toxicity. Our work on the microenvironment-triggered hydrogels with enhanced NIR imaging and easy metabolism may provide a promising strategy for sensitive and noninvasive imaging and phototherapy in ocular tumors.

A randomised, parallel-group comparison study of diquafosol ophthalmic solution in patients with dry eye in China and Singapore.

AIMS: To compare the efficacy and safety of 3% diquafosol ophthalmic solution with those of 0.1% sodium hyaluronate ophthalmic solution in patients with dry eye in China and Singapore. METHODS: A total of 497 patients with dry eye (Schirmer's test, 5 mm; fluorescein and RB score, 3 points) from China and Singapore were randomised to receive either diquafosol ophthalmic solution (diquafosol) or sodium hyaluronate ophthalmic solution (HA) at 1:1 ratio. The fluorescein staining scores and rose bengal (RB) subjective symptom scores and tear film breakup time were evaluated before treatment and 2 and 4 weeks after start of treatment. RESULTS: In the diquafosol group, changes in fluorescein and RB scores compared with baseline at week 4 or at the time of discontinuation were -2.1±1.5 and -2.5±2.0, respectively. Compared with the HA group, changes in fluorescein score were non-inferior and changes in RB score were superior (p=0.019). In addition, diquafosol and HA improved tear film breakup time by 1.046±1.797 and 0.832±1.775 s, respectively (no significant intergroup difference). Adverse event onset rates were 16.3% (40 of 246 subjects) and 10.0% (25 of 251 subjects) in the diquafosol group and HA group, respectively, with borderline significant intergroup differences (p=0.046), while adverse drug reaction incidence rates were 12.2% (30 of 246 subjects) and 6.0% (15 of 251 subjects), respectively (p=0.019). Only mild adverse drug reactions (>2%) in the form of eye discharge, itching or irritation were observed. CONCLUSIONS: Diquafosol improved fluorescein staining score in a manner similar to HA, and significantly improved RB score compared with HA. TRIAL REGISTRATION NUMBER: NCT01101984.

[Additive therapeutic effect of a combination of artemether and daphnetin against Plasmodium berghei in mice].

OBJECTIVE: To investigate the therapeutic effect of a combination of artemether and daphnetin against Plasmodium berghei ANKA strain in mice. METHODS: Groups of P. berghei infected mice were treated with various oral doses of artemether and daphnetin according to "4-day suppress assay". Thin blood smears were made on the fifth day after inoculation of parasites and the parasitemia reduction rate was calculated. The ED50 values obtained were plotted on isobolograms. A combined action of artemether and daphnetin was assessed. RESULTS: Artemether 0.4 mg/(kg x d) x 4d exhibited no detectable antimalarial effect, while artemether 0.4 mg/(kg x d) x 4d combined with daphnetin 7.7 mg/kg. d x 4d showed potent antiparasile efficacy. The ED50s of artemether in combination with daphnetin were lower than that of single artemether or daphnetin. The R-values were higher than 0.4, but lower than 2.7. CONCLUSION: The combination of artemether with daphnetin showed an additive antiparasile effect.