The intricate anatomical architecture and complex dynamic physiological barriers of the eye severely restrict the intraocular bioavailability of ophthalmic drugs. The limited absorption efficiency of conventional eye drops(<5%)and the highly invasive nature of intravitreal injections remain persistent bottlenecks in ophthalmic therapeutics. Driven by the convergence of materials science and biomedical engineering, intelligent stimuli-responsive drug delivery systems offer revolutionary strategies to overcome these physiological barriers and achieve spatiotemporally controlled drug release. These systems leverage specific recognition and response capabilities targeted at pathological microenvironments or exogenous physical fields. This article systematically reviews recent advances in this domain, providing an in-depth analysis of the physicochemical mechanisms underlying various stimuli-responsive carriers from the perspectives of polymer phase transition thermodynamics and chemical bond cleavage kinetics. By synthesizing preclinical and clinical research data on major ocular diseases, including glaucoma, age-related macular degeneration, and intraocular infections, the significant advantages of these intelligent systems were demonstrated. Highlighted benefits include prolonged ocular surface retention, biomarker-triggered on-demand release, and minimized systemic toxicity. Finally, this review critically analyzes the challenges of translating these complex formulations to the clinic, specifically regarding sterile scale-up manufacturing and regulatory approval pathways, while providing perspectives on future development.

Background Ozone (O₃), a key air pollutant, significantly contributes to cardiovascular disease (CVD)-related mortality, with particularly pronounced effects in the elderly. Objective To explore the association between acute O₃ exposure and mortality from CVD and its subtypes in the elderly population in Jinan, and to investigate the modifying effects of gender,age, and seasonal factors on O₃-related effects, as well as to clarify the interaction with other air pollutants. Methods Daily mortality data for CVD, air pollutants, and meteorological parameters were collected in Jinan from 2015 to 2023. Generalized additive models (GAM) combined with distributed lag nonlinear models (DLNM) were used to analyze the lag effects of acute O₃ exposure on mortalities from CVD, ischemic heart disease (IHD), and stroke in elderly individuals aged ≥60 years. Subgroup analyses were conducted to explore effect differences by gender (male vs. female), age (non-high-aged elderly<80 years vs. high-aged elderly ≥80 years), and season (warm season: April–September vs. cold season: October–March of the following year). Relative excess risk due to interaction (RERI), attributable proportion of interaction (API), and Synergy index (SI) were used to assess the interactions of O₃ with PM_2.5 and NO₂. Results During the study period, the mean daily concentration of ozone reached (105.01 ± 54.18) μg·m⁻³, exceeding the Grade I limit value specified in Ambient Air Quality Standard (GB 3095–2012). Among the 203834 CVD deaths, IHD (53.07%) and stroke (33.33%) were the predominant mortality subtypes. The single-day lag analysis revealed peak excess risk (ER) for CVD mortality at lag0 (ER=0.64%, 95%CI: 0.29%, 1.00%) per 10 μg·m⁻³ O₃ increase. The cumulative effects peaked at lag04 (ER=1.61%, 95%CI: 0.77%, 2.46%). The subtype-specific analyses showed the maximal single-day effects at lag0 were identified for both IHD (ER=0.61%, 95%CI: 0.20%, 1.03%) and stroke (ER=0.65%, 95%CI: 0.19%, 1.11%), while the cumulative risks peaked at lag04 for IHD (ER=1.54%, 95%CI: 0.56%, 2.54%) and lag03 for stroke (ER=1.74%, 95%CI: 0.76%, 2.73%). The gender subgroup analyses suggested that both male and female subgroups showed the most significant impact on CVD mortality at lag0, with ER values of 0.53% (95%CI: 0.11%, 0.95%) and 0.75% (95%CI: 0.33%, 1.18%), respectively, but the differences were not statistically significant (P>0.05). No statistically significant difference in effect values was found between high-aged and non-high-aged elderly (P>0.05) after age subgroup analyses. The seasonal subgroup analyses indicated that the effects of O₃ on CVD and its subtypes in the warm season were significantly higher than those in the cold season (P<0.05). At lag0 in the warm season, the ER values for CVD, IHD, and stroke mortality were 0.86% (95%CI: 0.57%, 1.14%), 0.84% (95%CI: 0.49%, 1.19%), and 0.84% (95%CI: 0.43%, 1.26%), respectively. The interaction analyses revealed an antagonistic effect between O₃ and PM_2.5 on stroke mortality in the elderly [RERI=−4.64% (95%CI: −9.27%, −0.01%), API=−4.39% (95%CI: −8.77%, −0.01%), SI=0.55 (95%CI: 0.26, 0.84)]. The O₃ effect remained robust in the multi-pollutant models (P<0.05). Conclusion Acute O₃ exposure increases the risk of mortality from CVD and its subtypes in the elderly, and this effect is amplified in the warm season. Additionally, O₃ and PM_2.5 have an antagonistic effect on stroke mortality in the elderly.

Background In recent years, regional high-temperature weather in summer occurs frequently in China. Heat stroke is the most representative meteorological disease caused by high temperature. In order to improve monitoring, early warning, prevention, and control of heat stroke, it is of great significance to understand the epidemiological characteristics of heat stroke and the associated impact of heatwave. Objective To understand the epidemiological characteristics of heat stroke cases in Jinan City, and to explore the effects of heatwave exposure on heat stroke. Methods Case reports of heat stroke and daily data of meteorological factors in Jinan City from 2017 to 2022 were collected. We described the temporal, population, and regional distribution characteristics of heat stroke cases in Jinan City, and used a time-stratified case-crossover design combined with conditional logistic regression model to explore the effects of heatwave exposure on heat stroke under 12 heatwave definitions (different combinations of intensity and duration). The cut-off percentiles used for heatwave definitions were the 90th (P₉₀), 95th (P₉₅), 97.5th (P_97.5), and 99th (P₉₉) percentiles of daily mean temperature; the durations were ≥ 2 d, ≥ 3 d, and ≥ 4 d, respectively. P_i(k), where i is temperature threshold, and k is duration. For example, the definition of a heatwave was notated as P₉₀(2), indicating that the daily mean temperature is ≥ P₉₀ and lasts for ≥ 2 d. Alternatively, lag01 denotes the cumulative lag effect with a 1 d lag, and so on. Results A total of 1394 cases of heat stroke were reported in Jinan City from 2017 to 2022, including 581 mild cases and 813 severe cases, and 85 deaths were reported, with a cumulative fatality rate of 6.10%. The cases of heat stroke reported each year during the study period were concentrated from June to August and peaked in July (665 cases, 47.70%). The sex ratio of males to females in heat stroke cases was 2.02:1. A high incidence of heat stroke was in 50-89 years, with a smaller peak occurring in the age group of 50-59 years and a larger peak in the age group of 70-79 years, respectively. The high-incidence areas of heat stroke were distributed in the western part of Jinan City where city centers situated (Tianqiao District, 274 cases, 19.66%; Huaiyin District, 223 cases, 16.00%) and in the surrounding rural areas (Pingyin County, 254 cases, 18.22%). The effect of heatwave exposure on heat stroke was statistically significant during the study period. The largest effect estimates for the effect on heat stroke occurred under the heatwave definitions of P₉₉(2), P_97.5(3), and P_97.5(4) at lag04, lag03, and lag04, where corresponding OR (95%CI) values were 9.27 (4.71, 14.24), 8.95 (6.17, 12.98), and 8.22 (4.91, 13.78), respectively. The exposure-response curve showed that the risk of heat stroke tended to increase with the increase of average daily temperature. Conclusion July is the key period for the occurrence of heat stroke among Jinan City residents, while male cases are predominant, more serious cases, age concentration in the 50-89 years. The occurrence of heatwave can further increase the risk of heat stroke with a significant lag effect.

Objective:To study the characteristics of the genotype and phenotypic in a family with X-linked retinoschisis (XLRS) due to RS1 mutation. Methods:A retrospective clinical study. An XLRS family of 4 generations of 26 people were included in the study. Among them, 8 participants were males and 7 participants were females. Routine ophthalmologic examination was performed on 3 patients in the family including the proband and 12 patients with normal phenotype. Optical coherence tomography was performed in 2 of the 3 patients. Peripheral venous blood was extracted from all participants, whole-genome DNA was extracted, and potential pathogenic genes were screened by Panel sequencing. Conservative analysis, pathogenicity analysis and protein structure prediction were carried out by software tools. The pathogenicity of gene mutations was analyzed according to the American Society of Medical Genetics and Genomics (ACMG) guidelines.Results:The proband was 3 years old. Optical coherence tomography (OCT) examination showed that the retinal core layer in the macular area of both eyes had a cystic change, which was segmented by vertical or oblique bridging tissue. The proband's uncle was 32 years old. OCT examination showed atrophy in the macular area of the left eye. The macular area of the right eye was cystoid, segmented by vertical or oblique bridging tissue. No abnormality was found in the fundus examination of the proband's parents and 10 members of his family. Panel sequencing showed that c.361C>T/ p.Q121X hemizygous mutation was found in the fifth exon of RS1 gene in the proband (Ⅳ3) and 2 patients (Ⅱ1, Ⅲ8). The mother was a heterozygous mutation carrier of the gene, while the father had no mutation. The mutant gene causes premature termination of RS1, a truncated protein encoding 224 amino acids to 120 amino acids. Of the 10 patients with normal fundus examination, 6 participants were normal. The mutation was carried by four people, which were women. Homology analysis of the protein sequence showed that the mutant site was highly conserved in 12 mammals. Three-dimensional structural analysis of RS1 protein showed that the c-terminal amino acid sequence of the mutant protein was more than 50% missing. Analysis of ACMG guidelines indicated that the mutation was pathogenic. Conclusion:The RS1 mutation site c.361C>T/p.Q121X is a new mutation site of XLRS.

Evaluate the effect of the fresh air purification system on the improvement of indoor PM 2.5 levels in a primary school classroom in Jinan City, Shandong Province. Our purpose is to explore the optimal operating time of the fresh air system and the main factors that affect the fresh air purification system to improve indoor air quality. From December 9, 2019 to December 10, 2019, two classrooms of the same area on the third floor of a primary school building in Jinan City, Shandong Province were selected as monitoring points. During the operation of the fresh air purification system, the PM 2.5 concentration in the classroom is reduced by an average of 48.1%-61.5% compared to the outdoor PM 2.5 concentration. After running for about 2 hours, the indoor PM 2.5 concentration decreased to a relatively stable concentration level. The operating time of the fresh air purification system, student activities between classes, indoor temperature, indoor relative humidity, and outdoor PM 2.5 concentration are important factors that affect the indoor particulate removal rate. In the case of a certain amount of fresh air and indoor area, closing doors and windows and appropriately extending the operation time of the fresh air purification system can improve the air quality in the classroom to a certain extent and protect the health of students.

Evaluate the effect of the fresh air purification system on the improvement of indoor PM 2.5 levels in a primary school classroom in Jinan City, Shandong Province. Our purpose is to explore the optimal operating time of the fresh air system and the main factors that affect the fresh air purification system to improve indoor air quality. From December 9, 2019 to December 10, 2019, two classrooms of the same area on the third floor of a primary school building in Jinan City, Shandong Province were selected as monitoring points. During the operation of the fresh air purification system, the PM 2.5 concentration in the classroom is reduced by an average of 48.1%-61.5% compared to the outdoor PM 2.5 concentration. After running for about 2 hours, the indoor PM 2.5 concentration decreased to a relatively stable concentration level. The operating time of the fresh air purification system, student activities between classes, indoor temperature, indoor relative humidity, and outdoor PM 2.5 concentration are important factors that affect the indoor particulate removal rate. In the case of a certain amount of fresh air and indoor area, closing doors and windows and appropriately extending the operation time of the fresh air purification system can improve the air quality in the classroom to a certain extent and protect the health of students.