Nanoparticles targeting the adenosine pathway for cancer immunotherapy.

Cancer immunotherapy, as an emerging approach to cancer treatment, has tremendous potential for application. Compared to traditional methods such as surgery, chemotherapy, and radiation therapy, it has the ability to restore the patient's immune system, leading to long-term immune memory with less damage to normal tissues. However, immunotherapy has its limitations, including limited therapeutic efficacy, restricted patient populations, and inconsistent treatment responses. Finding effective immunotherapeutic approaches has become a key focus of its clinical application. The adenosine pathway is a recently discovered tumor immune regulatory signaling pathway. It can influence the metabolism and growth of tumor cells by acting through key enzymes in the adenosine pathway, thereby affecting the development of tumors. Therefore, inhibiting the adenosine pathway is an effective cancer immunotherapy. Common adenosine pathway inhibitors include small molecules and antibody proteins, and extensive preclinical trials have demonstrated their effectiveness in inhibiting tumor growth. The short half-life, low bioavailability, and single administration route of adenosine pathway inhibitors limit their clinical application. With the advent of nanotechnology, nano-delivery of adenosine pathway inhibitors has addressed these issues. Compared to traditional drugs, nano-drugs extend the drug's circulation time and improve its distribution within the body. They also offer targeting capabilities and have low toxic side effects, making them very promising for future applications. In this review, we discuss the mechanism of the adenosine pathway in tumor immune suppression, the clinical applications of adenosine pathway inhibitors, and nano-delivery based on adenosine pathway inhibitors. In the final part of this article, we also briefly discuss the technical issues and challenges currently present in nano-delivery of adenosine pathway inhibitors, with the hope of advancing the progress of adenosine inhibitor nano-drugs in clinical treatment.

Potential Exploration of Biocompatible Carbon-Coated MoSe2 Nanoparticles for Exploration of the Photothermal Potential in the Treatment of Human Choriocarcinoma.

Background: Molybdenum diselenide (MoSe2), as a nano near-infrared absorber, has been widely studied in the field of photothermal therapy of cancer. However, there is little research on its application in the treatment of human choriocarcinoma. Methods and Results: In this paper, a new type of carbon-coated MoSe2 (MEC) nanoparticles was prepared by a one-step hydrothermal method. The chemical characterization including SEM, TEM, EDS, XRD, FT-IR, TGA, Roman, and XPS showed that MEC was successfully synthesized. MEC exhibited a high photothermal conversion efficiency (50.97%) and extraordinary photothermal stability under laser irradiation. The cell experiment results showed that MEC had good biocompatibility on normal cells while significant photothermal effect on human choriocarcinoma (JEG-3) cells, achieving a good anticancer effect. The level of reactive oxygen species (ROS) in JEG-3 cells was significantly increased under the combination of MEC nanoparticles and near-infrared radiation. MEC nanoparticles could induce apoptosis of JEG-3 cells in combination with near-infrared radiation. Finally, transcriptomic analysis verified that MEC combined with laser radiation could inhibit DNA replication and induce apoptosis, thus improving its therapeutic effect on human choriocarcinoma. Conclusion: MEC nanoparticles exert an excellent photothermal effect and may become an important candidate drug for the treatment of human choriocarcinoma.

Leveraging green finance and technological innovations for sustainable urban development: A comparative study of Chinese mega-cities.

Being worlds' largest population, China is the biggest consumer of natural resources and causes the highest Carbon emissions due to its energy needs for economic development. This research aims to analyze the relationship between green finance, natural resources, carbon releases, and foreign direct investment on China's efforts towards durable economic sustainability. Difference-in-Difference frameworks are utilized to analyze the statistics acquired from 270 Chinese cities between 2002 and 2022. The findings indicate that the financial implications of carbon emissions significantly affect China's sustainable green economy. However, the short-term growth of the green economy is enhanced by the use of natural resources and the advancement of green financial markets. The results of this study provide empirical evidence that supports the theory positing a linear association among carbon releases, economic expansion, and natural resources. This study provides guidance to policymakers to make policies for enhanced and efficient use of natural resources. This may potentially contribute to the promotion of long-term sustainability in China and the facilitation of green growth.

Carbon-coated selenium nanoparticles for photothermal therapy in choriocarcinoma cells.

Choriocarcinoma can be cured by chemotherapy, but this causes resistance and severe side effects that bring about physical and psychological consequences for patients. Therefore, there is still an urgent need to find other alternative minimally invasive therapies to halt the progression of choriocarcinoma. Novel carbon-coated selenium nanoparticles (C-Se) were successfully synthesized for choriocarcinoma photothermal therapy. C-Se combined with near-infrared laser irradiation can inhibit the proliferation of human choriocarcinoma (JEG-3) cells and induce cell apoptosis. C-Se killed cells and produced ROS under near-infrared laser irradiation. Finally, the therapeutic mechanism of C-Se + laser was explored showing that C-Se + laser influenced numerous biological processes. Taken together, C-Se exhibited significant potential for choriocarcinoma photothermal therapy.

Deep learning-based estimation of axial length using macular optical coherence tomography images.

Background: This study aimed to develop deep learning models using macular optical coherence tomography (OCT) images to estimate axial lengths (ALs) in eyes without maculopathy. Methods: A total of 2,664 macular OCT images from 444 patients' eyes without maculopathy, who visited Beijing Hospital between March 2019 and October 2021, were included. The dataset was divided into training, validation, and testing sets with a ratio of 6:2:2. Three pre-trained models (ResNet 18, ResNet 50, and ViT) were developed for binary classification (AL ≥ 26 mm) and regression task. Ten-fold cross-validation was performed, and Grad-CAM analysis was employed to visualize AL-related macular features. Additionally, retinal thickness measurements were used to predict AL by linear and logistic regression models. Results: ResNet 50 achieved an accuracy of 0.872 (95% Confidence Interval [CI], 0.840-0.899), with high sensitivity of 0.804 (95% CI, 0.728-0.867) and specificity of 0.895 (95% CI, 0.861-0.923). The mean absolute error for AL prediction was 0.83 mm (95% CI, 0.72-0.95 mm). The best AUC, and accuracy of AL estimation using macular OCT images (0.929, 87.2%) was superior to using retinal thickness measurements alone (0.747, 77.8%). AL-related macular features were on the fovea and adjacent regions. Conclusion: OCT images can be effectively utilized for estimating AL with good performance via deep learning. The AL-related macular features exhibit a localized pattern in the macula, rather than continuous alterations throughout the entire region. These findings can lay the foundation for future research in the pathogenesis of AL-related maculopathy.

PREDICTIVE ROLES OF QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES IN PROGNOSIS OF MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To explore the predictive roles of the morphologic features of neovascularization in the prognosis of myopic choroidal neovascularization. METHODS: In this retrospective case series study, quantitative morphologic features of neovascularization were obtained from the optical coherence tomography angiography images. According to the number of anti-vascular endothelial growth factor injections administered within 1 year, the eyes were classified into a stable group (≤2 injections) or an unstable group (>2 injections). Best-corrected visual acuity was recorded before the treatment and at the 1-year follow-up. RESULTS: Overall, 50 eyes with treatment-naive myopic choroidal neovascularization were included; 26 in the stable group and 24 in the unstable group. Multivariate analysis showed that the eyes in the unstable group were associated with a larger lesion area (odds ratio = 2.596, P = 0.012), higher junction density (odds ratio = 1.611, P = 0.014), and higher end point density (odds ratio = 1.435, P = 0.023).The area under the receiver operating characteristic curve of the multivariate model was 0.865, with 91.7% sensitivity and 65.4% specificity. The final best-corrected visual acuity was significantly correlated with the lesion area (ß = 0.152, P = 0.032) after adjusted for age, sex, and baseline best-corrected visual acuity. CONCLUSION: Lesions with larger areas and higher end point and junction densities tended to have more frequent anti-vascular endothelial growth factor injections and worse visual outcomes in eyes with myopic choroidal neovascularization.

The efficacy of micropulse laser combined with ranibizumab in diabetic macular edema treatment: study protocol for a randomized controlled trial.

BACKGROUND: At present, intraocular injection of anti-VEGF (vascular endothelial growth factor) drugs has replaced traditional laser therapy as the first-line treatment for DME (diabetic macular edema). However, ranibizumab, a commonly used anti-VEGF drug, is expensive and requires multiple intraocular injections. It places a heavy economic burden on patients with DME. Micropulse laser is safer than conventional laser and can reduce edema. Combined treatment with anti-VEGF may reduce the number of intraocular injections. This study will compare the efficacy of micropulse laser combined with ranibizumab treatment to ranibizumab monotherapy in the treatment of DME, providing a new regimen for future DME treatment. METHODS: This study is a prospective randomized double-blind controlled clinical trial (RCT) in patients with DME. After 1-year follow-up, visual acuity and macular edema regression will be compared between micropulse laser combined with ranibizumab group and ranibizumab monotherapy group to determine whether the efficacy of micropulse laser combined with ranibizumab treatment was not lower than that of ranibizumab monotherapy in the treatment of DME. Visual acuity measured by the ETDRS chart is the primary outcome measure. The secondary outcome measures are CMT (central macular thickness) measured by OCT (optical coherence tomography) and the number of injections of two groups. Changes in visual acuity and CMT of the two groups will be compared at 12-month follow-up. Before patients are recruited, we provide them with informed consent, in which we explain to them the purpose and process of the study. DISCUSSION: Micropulse laser combined with anti-VEGF drugs in the treatment of DME can reduce the number of intravitreal anti-VEGF injections, not only relieve the pain of the patients, but also ease the economic and psychological burden of patients, bringing great benefits. However, there is no treatment consensus for the parameters and specific methods of micropulse laser treatment for DME. There is a lack of clinical research data reference of micropulse laser combined with anti-VEGF therapy in clinical practice. This study intends to provide a new direction for clinical DME treatment and also provide a realistic consideration for the application of micropulse laser in DME treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03690947. Registered on 1 October 2018.

Structural and Visual Changes in Branch Retinal Vein Occlusion Patients with Retinal Atrophy.

Background: To study the changes of retinal vascular density (VD), retinal thickness (RT), and their correlations with visual acuity (VA) in branch retinal vein occlusion (BRVO) patients with retinal atrophy after resolution of macular oedema (MO). Methods: This is a retrospective study consisting of 46 patients diagnosed with BRVO at Beijing Hospital from 2015 to 2019. Patients' 46 affected eyes and 39 fellow eyes were included. The affected eyes were further divided into the atrophy group and the nonatrophy group. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images obtained when MO completely resolved after treatment with ranibizumab were analyzed. We quantitatively measured foveal avascular zone (FAZ) parameters, the disruption extent of ellipsoid zone (EZ), RT, and VD of superficial vascular complex (SVC), and deep vascular complex (DVC) in central fovea and the minimal-VD quadrant. Paired t-tests, independent t-tests, Mann-Whitney U tests, Wilcoxon tests, Pearson correlation analyses, Spearman correlation analyses, and single and multiple linear regression models were adopted. Results: Compared with nonatrophy eyes, the minimal-VD quadrantal (quadrantal for short) SVC-VD (25.76 ± 4.57% versus 36.21 ± 6.47%, P < 0.001) and quadrantal DVC-VD (27.72 (17.23) % versus 38.95 (11.05) %, P = 0.001) of atrophy eyes decreased significantly. Quadrantal SVC-VD and quadrantal DVC-VD were strongly correlated with quadrantal full RT (r = 0.763 and 0.698, both P < 0.001). The disruption length of EZ was significantly correlated with quadrantal full RT (r = -0.406, P = 0.005) and quadrantal SVC-VD (r = -0.298, P = 0.044). In multiple linear regression analysis, the disruption length of EZ and VA before treatment and age showed significant correlations with VA with complete resolution of MO (P = 0.020, 0.033, and 0.002). Conclusions: The retinal VD on the affected area correlates well with the corresponding full RT when BRVO-MO completely resolves, suggesting that VD may predict the final RT. Severe decrease in VD may result in retinal atrophy, which may cause VA loss indirectly with the intermediate influencing factor of EZ defects.

Microvascular impairments detected by optical coherence tomography angiography in multiple sclerosis patients: A systematic review and meta-analysis.

Purpose: A systematic review and meta-analysis was conducted to investigate changes in retinal and choroidal microvasculature in patients with multiple sclerosis (MS) using optical coherence tomography angiography (OCTA). Methods: PubMed and Google Scholar were searched for studies that compared retinal and choroidal microvasculature between MS and healthy controls (HC) with OCTA. MS patients were divided into 2 groups: MS with (MSON) or without optic neuritis (MSNON). Results: Totally, 13 studies including 996 MS eyes and 847 HC eyes were included. Compared with the HC, the vessel density of the whole superficial vascular complex (SVC) was reduced by 2.27% and 4.30% in the MSNON and MSON groups, respectively. The peripapillary vessel density was 2.28% lower and 4.96% lower in the MSNON and MSON groups, respectively, than in the HC. Furthermore, the MSON group had significant lower vessel density of the SVC (mean difference [MD] = -2.17%, P < 0.01) and lower peripapillary vessel density (MD = -2.02%, P = 0.02) than the MSNON group. No significant difference was found in the deep vascular complex or choriocapillaris densities among MSNON, MSON or HC groups (P > 0.05). Meta-regression analyses suggested that illness duration and the Expanded Disability Status Scale scores of MS patients were possible sources of heterogeneity (P < 0.05). Conclusion: The retinal SVC and peripapillary vessel density decreased significantly in MS eyes, especially in eyes with optic neuritis. Retinal microvasculature is a potential biomarker of disease progression in MS.

Correlation between the Nonperfusion Area on Ultra-Widefield Fluorescein Angiography and Nonflow Area on Optical Coherence Tomographic Angiography in Retinal Vein Occlusion.

AIMS: To compare the relationship between the nonperfusion area (NPA) on ultra-widefield fluorescein angiography (UWFFA) and the nonflow area (NFA) on optical coherence tomographic angiography (OCTA) in retinal vein occlusion (RVO). METHODS: Cross-sectional study. 46 eyes of 46 RVO patients who underwent UWFFA and OCTA. NPA and ischemic index (ISI) were quantified on UWWFA. NFA, vessel density (VD) of the superficial capillary plexus (SCP), the deep capillary plexus (DCP), and the size foveal avascular zone (FAZ) on 3 ∗ 3 mm OCTA were measured. The association of the NPA and ISI on UWWFA and the parameters on OCTA were analyzed. Spearman correlation was used for statistical testing. RESULTS: The NPA and ISI on UWFFA were significantly correlated with the NFA on OCTA in RVO, and r values were 0.688 (p < 0.01) and 0.680 (p < 0.01), respectively. VD in the SCP of the temporal quadrant was negatively correlated with NPA and ISI, and r values were -0.346 (p < 0.05) and -0.337 (p < 0.05), respectively. VD in the DCP of the temporal quadrant was negatively correlated with the NPA, and the r value was -0.246 (p < 0.05). No significant correlation was found between the NPA and ISI on UWFFA and VD of other quadrants in the SCP or DCP and the FAZ area on OCTA. CONCLUSION: NPA in the peripheral retina was correlated with NFA in macula. NFA detected by OCTA could be an indicator of the ischemic status in RVO.

Combination of Ranibizumab with macular laser for macular edema secondary to branch retinal vein occlusion: one-year results from a randomized controlled double-blind trial.

BACKGROUND: It is not clear whether macular laser combined with anti-vascular endothelial growth factor (VEGF) can reduce the number of anti-VEGF injections in the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Our study aimed to investigate the effects of intravitreal ranibizumab with or without macular laser for ME secondary to BRVO and its associated number of anti-VEGF injections. METHODS: This is a prospective, randomized, double-blind, monocentric trial.80 patients were enrolled and 64 patients fulfilled the study requirements. All patients received a minimum of 3 initial monthly ranibizumab injections, pro re nata (PRN) dosing thereafter VA and CRT stabilization criteria-driven PRN treatment. Laser was given 7 days after third ranibizumab injection in ranibizumab with laser group. The follow-up time of this study was 1 year. Best corrected visual acuity (BCVA) improvement, central retinal thickness (CRT) reduction and number of injections of patients were compared between two groups. T-test, non-parametric Wilcoxon test and chis-square tests were adopted for between-group comparisons. RESULTS: Thirty patients received intravitreal ranibizumab 0.5 mg alone and 34 patients received intravitreal ranibizumab 0.5 mg with macular laser. At 52 week, BCVA increased significantly and CRT decreased significantly in both groups (P < 0.001). However, there was no significant difference in BCVA improvement with baseline BCVA adjusted (p = 0.5226), and in the CRT reduction (P = 0.4552) between two groups after 52 weeks. There was also no significant difference in the number of injections between the two groups. (P = 0.0756). There was also no significant difference between ischemic and non-ischemic groups in BCVA improvement, CRT reduction and number of injections (P > 0.05). CONCLUSIONS: Our study suggests that ranibizumab combined with macular laser is effective in the treatment of ME secondary to BRVO after 1 year of treatment with 3 + PRN regimen. However, combination of macular grid photocoagulation showed no beneficial anatomical or functional effect during follow-up period, nor did it reduce the number of ranibizumab injections, either in ischemic group or non-ischemic group. We suggest that there is no need to combine macular grid photocoagulation in the treatment of ME secondary to BRVO in the future. TRIAL REGISTRATION: Clinical Trials NCT03054766. https://register.clinicaltrials.gov.Prospectively registered.

Quantification of Microvascular Density of the Optic Nerve Head in Diabetic Retinopathy Using Optical Coherence Tomographic Angiography.

AIMS: To quantify the capillary density of the optic nerve head in healthy control eyes and different stages of diabetic retinopathy (DR) eyes and identify the parameters to detect eyes with or without DR using optical coherence tomographic angiography (OCTA). METHODS: In this cross-sectional study, 211 eyes of 121 participants with type 2 diabetes with different stages of DR or without DR and 73 eyes of 38 healthy age-matched controls were imaged by OCTA. Radial peripapillary capillary (RPC) plexus density and retinal nerve fiber layer (RNFL) thickness were examined. The mixed model binary logistic regression model was used to identify the parameters to detect eyes with or without DR. The area under the receiver operating characteristic (ROC) curve was calculated. RESULTS: RPC density decreased significantly in diabetic patients without DR compared with the healthy controls, and it was negatively correlated with the severity of DR (P < 0.01). RPC density was a significant parameter to distinguish diabetic eyes with or without DR (P < 0.01). The area under the ROC curve was 0.743. CONCLUSIONS: Quantification of RPC density by OCTA provides evidence of microvascular changes in the optic nerve in diabetic patients. RPC density can serve as a possible biomarker in detecting eyes with DR. Larger cohort studies need to support this statement.

Therapeutic effects of ranibizumab in patients with polypoidal choroidal vasculopathy.

BACKGROUND: There is no consensus on the optimal initial treatment for polypoidal choroidal vasculopathy (PCV). Our study aimed to report the efficacy of repeated injections of intravitreal ranibizumab with or without photodynamic therapy for the treatment of PCV and to determine the possible factors predictive of visual outcomes. METHODS: The results of the initial treatment of 40 patients with PCV with 3 monthly injections of ranibizumab were retrospectively reviewed. We compared the results in terms of the best corrected visual acuity (BCVA), the central retinal thickness (CRT), the number of injections, the regression rates of polyps and the rates of the reduction of subretinal fluid. RESULTS: At the 3-month follow-up, the mean BCVA was significantly increased by 7.3 ± 12.4 letters compared to baseline (p < 0.01). At the 12-month follow-up, the mean BCVA was increased by 3.4 ± 15.4 letters compared to baseline, and there was no significant difference (p > 0.05). The mean CRT at the 12-month follow-up was 593.58 ± 243.64 µm, with an average decrease of 101.55 ± 256.07 µm compared to baseline (p < 0.01). Fifteen eyes (18.8%) showed the complete regression of polyps, and 22 eyes (27.5%) showed a reduction in polyps. The baseline VA, the reduction in subretinal fluids and the greatest lesion diameter were significant independent factors that were predictive of improved VA at the final follow-up. CONCLUSIONS: Three monthly injections of ranibizumab as an initial treatment could significantly improve VA in PCV patients in the short term. At 12 months postinjection, ranibizumab treatment could stabilize VA in most PCV patients. The baseline VA, the reduction in subretinal fluids and the greatest lesion diameter were predictive factors for the relative improvement of VA at the final follow-up.

Intravitreal Dexamethasone Implant versus Intravitreal Ranibizumab for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion in a Chinese Population.

BACKGROUND: The aim of this work was to compare the efficacy of intravitreal dexamethasone implant (Ozurdex) and intravitreal ranibizumab (Lucentis) in the treatment of macular edema (ME) caused by retinal vein occlusion (RVO). METHODS: Thirty-two ME cases treated with Ozurdex and 32 ME cases treated with ranibizumab were enrolled, with 26 central (C)RVO and 6 branch (B)RVO subjects in each group. We compared the results of best-corrected visual acuity (BCVA), central retinal thickness, number of injections, and intraocular pressure (IOP) at 1, 2, 3, and 6 months after injection. RESULTS: BCVA in both groups at each follow-up were significantly increased compared to baseline with no statistical difference between the groups. Ozurdex and ranibizumab successfully reduced CMT at each follow-up. Both CRVO and BRVO patients had significant between-group differences in the mean number of injections. Among the CRVO patients, IOP in the Ozurdex group was significantly increased compared to baseline and the ranibizumab group at 1, 2, and 3 months postinjection. CONCLUSIONS: Intravitreal injection of Ozurdex and ranibizumab can effectively control ME secondary to RVO and increase a patient's BCVA. The advantages of Ozurdex are fewer injections and longer efficacy, while the advantages of ranibizumab include fewer side effects.

Intravitreal injection of ranibizumab for treatment of age-related macular degeneration: effects on serum VEGF concentration.

AIMS: To evaluate potential adverse ranibizumab-related systemic events through analysis of variations in serum levels of vascular endothelial growth factor (VEGF) in neovascular age-related macular degeneration (AMD) patients before and after a single intravitreal injection of ranibizumab. METHODS: Thirty-nine patients with neovascular AMD and 39 healthy control subjects were enrolled in the study. Patients received a single intravitreal injection of ranibizumab (0.5 mg) in one eye. Venous blood was collected and placed in coagulation-promoting tubes 1 day before and on post-injection days 1, 3, 7 and 30. Serum concentrations of VEGF were measured by ELISA at each time point. RESULTS: VEGF concentrations were 323.64 pg/ml in AMD patients and 392.94 pg/ml in control subjects before injection (p > 0.05). VEGF significantly decreased to 304.65 pg/ml 1 day later (p < 0.05) in AMD patients, then increased to 310.77 (p > 0.05), 317.89 (p > 0.05) and 311.79 pg/ml (p > 0.05) on post-injection days 3, 7 and 30, respectively. CONCLUSION: No significant changes in serum levels of VEGF were found from 3 to 30 days following a single intravitreal ranibizumab injection. Although certain influences existed 24-h post-injection, effect(s) of a single intravitreal ranibizumab injection on the homeostasis of the cardiovascular system during such a brief period is unknown.