Diseases of ocular fundus are the leading causes of severe vision impairment or even blindness in patients worldwide, and the medical treatments are seriously limited by the difficulty of therapeutic drugs entering the fundus due to the various physiological barriers. Nano-drug delivery systems, with their nanoscale size and large surface area, can be loaded with therapeutic drugs of different physicochemical properties and modified with various surface active substances, which can not only improve the solubility and penetration of the drugs, but also protect biologic drugs from degradation and improve the biological safety and bioavailability, as well as deliver therapeutic drugs to specific ocular targets. All of these make the therapeutic potential enormous. Currently, more and more studies have been carried out to take advantage of nanomaterials for the treatment of different fundus diseases, including neurodegenerative diseases, fundus neovascularization, endophthalmitis and fundus tumors. This review analyzes the challenges and barriers faced by different routes of drug administration in the treatment of fundus diseases, the physicochemical properties of common nano-drug delivery systems that have been studied in related fields, and further summarizes the progress, advantages, limitations, and future directions of the application of various nano-drug delivery systems for the treatment of ocular fundus diseases in recent years.

Objective To investigate the microbiome composition of deep invasive endometriosis lesions,offering novel insights into its pathogenesis,diagnosis,and treatment strategies.Methods From May 2021 to May 2022,we collected samples of normal endometrium(normal group,n=10),endometrium from patients with deep infiltrating endometriosis(DIE endometrium group,n=14),and lesions from these patients(DIE lesion group,n=10)for 16s rRNA sequencing analysis.We employed the bacterial community diversity algorithm(alpha diversity and beta diversity),principal coordinate analysis(PCoA)distance matrix algorithms(Bray-Curtis and Unifrac matrices),as well as the biological identification algorithm(LeFSe)to investigate microbiome differences between groups and identify differentially abundant bacteria and enriched KEGG functions.Results The diversity of the three groups did not show any significant difference,while the β diversity exhibited a statistically significant distinc-tion(P=0.005 5).The focus group had a relatively low abundance of Firmicutes at the phylum level and a relatively increased abundance of Fusobacteria.At the genus level,there was an increased relative abundance of Enterococcus and Prevotella.LEFse analysis suggested that Proteobacteria and Gammaproteobacteria were the main dominant in the lesion group.Notably,Gamma proteobacteria emerged as a key differential species among the three groups'microbial flora with statistical significance(P=0.021 2).Conclusion Compared to the normal group and DIE group,there was a significant increase in the abundance of Fusobacteria,Proteobacteria,Gammaproteobacteria,Enterococcus,and Prevotella.These findings offer novel therapeutic targets for the prevention and intervention of deep infiltrating endometriosis.

Objective:To investigate the impact of exogenous lactate on the replication of dengue virus type 2 (DENV-2) in Raw264.7 cells, mouse bone marrow-derived macrophages (BMDMs) and THP-1 cells and explore its association with cell activation.Methods:BMDMs from BALB/c mouse bone marrow were prepared and evaluated by flow cytometry to detect the proportion of F4/80 + CD11b + cells. Glucose transporter type 1 (GLUT1), hexokinase 2 (HK2), and monocarboxylate transporters 4 (MCT4) expression at mRNA level in BMDMs at different time points after DENV-2 infection were measured by qRT-PCR. The content of lactate in the culture supernatants was quantified via colorimetric assay. CCK-8 assay was used to evaluate the impacts of different concentrations of lactate on the viability of Raw264.7 cells, BMDMs, and THP-1 cells. qRT-PCR was used to detect the expression of DENV-2 E gene, TGF-β, CD86, retinoic acid-inducible gene Ⅰ (RIG-Ⅰ), IFN-β, interferon-stimulated gene 15 (ISG15), and ISG56 at mRNA level in cells infected with DENV-2 at different MOIs in the presence of different concentrations of lactate. Meanwhile, flow cytometry was used to analyze the expression of CD86 and CD206. Results:The percentage of BMDMs was (87.53±1.66)%. GLUT1 expression at mRNA level exhibited a decrease in BMDMs at 24 h after DENV-2 (MOI=3) infection following a transient increase at 12 h ( P<0.05), while HK2 expression at mRNA level was higher that than in blank control and inactivated DENV-2 infection groups at 12, 24, and 36 h ( P<0.01). Besides, there was an increase in both MCT4 mRNA level and the content of lactate in culture supernatants at 24 h after DENV-2 (MOI=1.5) infection ( P<0.05). The viability of the three types of cells remained above 80% when the concentration of lactate was 31.25 mmol/L. Lactate at the concentration of 35 mmol/L increased the expression of the DENV E gene at mRNA level in DENV-2-infected BMDMs at MOI=1 or MOI=2 ( P<0.05). Besides, it promoted the expression of DENV E gene at mRNA level in Raw264.7 and THP-1 cells ( P<0.001) as well as the expression of CD163, TGF-β, RIG-Ⅰ, IFN-β, ISG15 and ISG56 at mRNA level in BMDMs at MOI=1.5, but inhibited the expression of CD86 at mRNA level in BMDMs ( P<0.05). It also up-regulated CD206 protein expression ( P<0.01) and down-regulated CD86 protein expression ( P>0.05) in BMDMs. Conclusions:Exogenous lactate enhances DENV-2 replication in both human- and murine-derived macrophages and that might correlate with M2 macrophage polarization.

Objective:To assess the impact of health insurance packaged payment in medical communities on the economicburden of patients,income and satisfaction of medical staff in counties.Methods:Using sample data from 2018-2022 from the national monitoring counties of medical communities,taking 2020 as the year of implementation of packaged payment,a double difference model was constructed with county population density and county per capita GDP as the control variables to assess the impact of packaged payment on the economic burden of patients,medical staff income and satisfaction in the county.Results:The packaged payment policy reduced the economic burden of patients to a certain extent and had a statistically significant positive effect on medical staff income in 2021,but it did not significantly increase the satisfaction of both supply and demand.Conclusion:The implementation of health insurance packaged payment of the MEC will not increase the economic burden of patients.It has a good pro-poor effect,and the income of medical staff has been improved to some extent,but there is still room for optimisation and improvement of the policy.

Objective:To assess the impact of health insurance packaged payment in medical communities on the economicburden of patients,income and satisfaction of medical staff in counties.Methods:Using sample data from 2018-2022 from the national monitoring counties of medical communities,taking 2020 as the year of implementation of packaged payment,a double difference model was constructed with county population density and county per capita GDP as the control variables to assess the impact of packaged payment on the economic burden of patients,medical staff income and satisfaction in the county.Results:The packaged payment policy reduced the economic burden of patients to a certain extent and had a statistically significant positive effect on medical staff income in 2021,but it did not significantly increase the satisfaction of both supply and demand.Conclusion:The implementation of health insurance packaged payment of the MEC will not increase the economic burden of patients.It has a good pro-poor effect,and the income of medical staff has been improved to some extent,but there is still room for optimisation and improvement of the policy.

Objective:To assess the impact of health insurance packaged payment in medical communities on the economicburden of patients,income and satisfaction of medical staff in counties.Methods:Using sample data from 2018-2022 from the national monitoring counties of medical communities,taking 2020 as the year of implementation of packaged payment,a double difference model was constructed with county population density and county per capita GDP as the control variables to assess the impact of packaged payment on the economic burden of patients,medical staff income and satisfaction in the county.Results:The packaged payment policy reduced the economic burden of patients to a certain extent and had a statistically significant positive effect on medical staff income in 2021,but it did not significantly increase the satisfaction of both supply and demand.Conclusion:The implementation of health insurance packaged payment of the MEC will not increase the economic burden of patients.It has a good pro-poor effect,and the income of medical staff has been improved to some extent,but there is still room for optimisation and improvement of the policy.

Objective:To assess the impact of health insurance packaged payment in medical communities on the economicburden of patients,income and satisfaction of medical staff in counties.Methods:Using sample data from 2018-2022 from the national monitoring counties of medical communities,taking 2020 as the year of implementation of packaged payment,a double difference model was constructed with county population density and county per capita GDP as the control variables to assess the impact of packaged payment on the economic burden of patients,medical staff income and satisfaction in the county.Results:The packaged payment policy reduced the economic burden of patients to a certain extent and had a statistically significant positive effect on medical staff income in 2021,but it did not significantly increase the satisfaction of both supply and demand.Conclusion:The implementation of health insurance packaged payment of the MEC will not increase the economic burden of patients.It has a good pro-poor effect,and the income of medical staff has been improved to some extent,but there is still room for optimisation and improvement of the policy.

Objective:To assess the impact of health insurance packaged payment in medical communities on the economicburden of patients,income and satisfaction of medical staff in counties.Methods:Using sample data from 2018-2022 from the national monitoring counties of medical communities,taking 2020 as the year of implementation of packaged payment,a double difference model was constructed with county population density and county per capita GDP as the control variables to assess the impact of packaged payment on the economic burden of patients,medical staff income and satisfaction in the county.Results:The packaged payment policy reduced the economic burden of patients to a certain extent and had a statistically significant positive effect on medical staff income in 2021,but it did not significantly increase the satisfaction of both supply and demand.Conclusion:The implementation of health insurance packaged payment of the MEC will not increase the economic burden of patients.It has a good pro-poor effect,and the income of medical staff has been improved to some extent,but there is still room for optimisation and improvement of the policy.

Objective:To assess the impact of health insurance packaged payment in medical communities on the economicburden of patients,income and satisfaction of medical staff in counties.Methods:Using sample data from 2018-2022 from the national monitoring counties of medical communities,taking 2020 as the year of implementation of packaged payment,a double difference model was constructed with county population density and county per capita GDP as the control variables to assess the impact of packaged payment on the economic burden of patients,medical staff income and satisfaction in the county.Results:The packaged payment policy reduced the economic burden of patients to a certain extent and had a statistically significant positive effect on medical staff income in 2021,but it did not significantly increase the satisfaction of both supply and demand.Conclusion:The implementation of health insurance packaged payment of the MEC will not increase the economic burden of patients.It has a good pro-poor effect,and the income of medical staff has been improved to some extent,but there is still room for optimisation and improvement of the policy.

Objective:To assess the impact of health insurance packaged payment in medical communities on the economicburden of patients,income and satisfaction of medical staff in counties.Methods:Using sample data from 2018-2022 from the national monitoring counties of medical communities,taking 2020 as the year of implementation of packaged payment,a double difference model was constructed with county population density and county per capita GDP as the control variables to assess the impact of packaged payment on the economic burden of patients,medical staff income and satisfaction in the county.Results:The packaged payment policy reduced the economic burden of patients to a certain extent and had a statistically significant positive effect on medical staff income in 2021,but it did not significantly increase the satisfaction of both supply and demand.Conclusion:The implementation of health insurance packaged payment of the MEC will not increase the economic burden of patients.It has a good pro-poor effect,and the income of medical staff has been improved to some extent,but there is still room for optimisation and improvement of the policy.