Retinoblastoma (RB) is prone to be delayed diagnosis or treatment and has an increased likelihood of metastasizing. Thus, it is crucial to perform an effective imaging examination and provide optimal treatment of RB to prevent metastasis. Nanoparticles that support diagnostic imaging and targeted therapy are expected to noninvasively integrate tumor diagnosis and treatment. Herein, we report a multifunctional nanoparticle for multimodal imaging-guided low-intensity focused ultrasound (LIFU)/immuno-synergistic RB therapy. Magnetic hollow mesoporous gold nanocages (AuNCs) conjugated with Fe3O4 nanoparticles (AuNCs-Fe3O4) were prepared to encapsulate muramyl dipeptide (MDP) and perfluoropentane (PFP). The multimodal imaging capabilities, antitumor effects, and dendritic cell (DC) activation capacity of these nanoparticles combined with LIFU were explored in vitro and in vivo. The biosafety of AuNCs-Fe3O4/MDP/PFP was also evaluated systematically. The multifunctional magnetic nanoparticles enhanced photoacoustic (PA), ultrasound (US), and magnetic resonance (MR) imaging in vivo and in vitro, which was helpful for diagnosis and efficacy evaluation. Upon accumulation in tumors via a magnetic field, the nanoparticles underwent phase transition under LIFU irradiation, and MDP was released. A combined effect of AuNCs-Fe3O4/MDP/PFP and LIFU was recorded and verified. AuNCs-Fe3O4/MDP/PFP enhanced the therapeutic effect of LIFU and led to direct apoptosis/necrosis of tumors, while MDP promoted DC maturation and activation, and activated the ability of DCs to recognize and clear tumor cells. By enhancing PA/US/MR imaging and inhibiting tumor growth, the multifunctional AuNCs-Fe3O4/MDP/PFP nanoparticles show great potential for multimodal imaging-guided LIFU/immuno-synergistic therapy of RB. The proposed nanoplatform facilitates cancer theranostics with high biosafety.

Aims: The purpose of this study is to investigate whether gene polymorphisms of the vascular endothelial growth factor A (VEGF-A) and its receptor (VEGFR-2) have a pharmacogenetics effect on the anti-VEGF treatment for neovascular age-related macular degeneration (nAMD).Methods: We carried out a meta-analysis focusing on the relationship between VEGF-related gene polymorphisms and treatment response of nAMD.Results: For the single nucleotide polymorphisms (SNPs) withinVEGF-AandVEGFR-2, anti-VEGF treatment was much more effective in patients with nAMD having rs833061 (CC vs TT:OR=2.222, 95% CI 1.252 to 3.944, p=0.006; CT vs TT: OR=2.537,95% CI 1.478 to 4.356, p=0.001 and CC vs CT+TT: OR=2.362, 95% CI 1.414 to 3.946, p=0.001), particularly for Asians (CC vs TT: OR=2.903, 95% CI 1.150 to 7.330, p=0.024; CT vs TT: OR=3.849, 95% CI 1.522 to 9.733, p=0.004 and CC vs CT+TT: OR=3.339, 95% CI 1.369 to 8.145, p=0.008, respectively). In subgroup analysis, rs833061 was more likely to be a predictor of response to anti-VEGF therapy specifically when ranibizumab (RBZ) only regime was adopted or visual acuity (VA) was taken as the standardised assessment of outcome. No association with response to anti-VEGF treatment was detected for the other eight polymorphisms.Conclusions: Pharmacogenetics ofVEGF-Apolymorphism rs833061 may play a positive role in response to anti-VEGF therapy for nAMD.

Graves’ disease (GD) is a common thyroid disease, and Graves ophthalmopathy(GO) is the most common extra-thyroidal manifestation of GD. Genetic associations of the thyroid stimulating hormone receptor (TSHR) gene with GD and GO have been studied in different population groups for a long time. We aimed to obtain a more precise estimation of the effects of TSHR single nucleotide polymorphisms (SNPs) on GD/GO using a meta-analysis. Publications were searched on Pub Med and EMBASE up to December 30, 2015. Eight studies involving three SNPs (rs179247, rs12101255, and rs2268458), which included 4790 cases and 5350 controls, met the selection criteria. The pooled odds ratios (OR) and the 95% confidence intervals (CI) were estimated. SNPs rs179247 (dominant model [GG + GA vs. AA]: OR = 0.66, 95%CI: 0.61–0.73, P = 0.000, I² = 0%) and rs12101255 (dominant model [TT + TC vs. CC]: OR = 1.67, 95%CI: 1.53–1.83, P = 0.000, I² = 0%) were significantly associated with GD in all of the genetic models. TSHR rs12101255 and rs2268458 polymorphisms had no association between GO and GD (GD without GO). The results indicate that rs179247 and rs12101255 are likely to be genetic biomarkers for GD. Further studies with different population groups and larger sample sizes are needed to confirm the genetic associations of the TSHR gene with GD/GO.

Retinoblastoma (Rb) represents 3% of all childhood malignancies and seriously endangers children's lives and quality of life. Early diagnosis and treatment can save children's vision as much as possible. Multifunctional nanoparticles have become a research hotspot in recent years and are expected to realize the integration of early diagnosis and early treatment. Therefore, we report a nanoparticle with dual-mode imaging, photothermal therapy, and immune activation: carbonized MOF nanoparticles (CM NPs) loaded with the immune polypeptide tuftsin (CMT NPs). The dual-mode imaging ability, antitumor effect, and macrophage immunity activation ability of these nanoparticles combined with laser irradiation were studied. The biosafety of CMT NPs was detected. The multifunctional magnetic nanoparticles enhanced photoacoustic (PA) and magnetic resonance (MR) imaging in vivo and in vitro, facilitating diagnosis and efficacy evaluation. The combined effect of CMT NPs and laser irradiation was recorded and verified. Through the accumulation of magnetic field nanoparticles in tumors, the photothermal conversion of nanoparticles under laser irradiation led directly to tumor apoptosis/necrosis, and the release of tuftsin induced macrophage M1-type activation, resulting in antitumor immune effects. Enhanced PA/MR imaging CMT NPs have great potential in dual-mode image-guided laser/immune cotherapy. The nanoparticles have high biosafety and have potential in cancer treatment.

Aims: This study aimed to develop and validate a risk nomogram prediction model based on the retinal geometry of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to investigate its clinical application value.Methods: In this study, we collected the clinical data of 410 patients with T2DM in the Second Affiliated Hospital of Chongqing Medical University between October 2020 and March 2022. Firstly, the patients were randomly divided into a development cohort and a validation cohort in a ratio of 7:3. Then, the modeling factors were selected using the least absolute shrinkage and selection operator (LASSO). Subsequently, a nomogram prediction model was built with these identified risk factors. Two other models were constructed with only retinal vascular traits or only clinical traits to confirm the performance advantage of this nomogram model. Finally, the model performances were assessed using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA).Results: Five predictive variables for DR among patients with T2DM were selected by LASSO regression from 33 variables, including fractal dimension, arterial tortuosity, venular caliber, duration of diabetes mellitus (DM), and insulin dosage (P< 0.05). A predictive nomogram model based on these selected clinical and retinal vascular factors presented good discrimination with an AUC of 0.909 in the training cohort and 0.876 in the validation cohort. By comparing the models, the retinal vascular parameters were proven to have a predictive value and could improve diagnostic sensitivity and specificity when combined with clinical characteristics. The calibration curve displayed high consistency between predicted and actual probability in both training and validation cohorts. The DCA demonstrated that this nomogram model led to net benefits in a wide range of threshold probability and could be adapted for clinical decision-making.Conclusion: This study presented a predictive nomogram that might facilitate the risk stratification and early detection of DR among patients with T2DM.