Reading English biomedical literature is a core competency for medical students, yet many rely heavily on full-text translation tools. Although translation appears to reduce language barriers, its impact on cognitive load and durable learning remains unclear. This study compared three reading modalities to evaluate their effects on cognitive load, immediate comprehension, and delayed vocabulary retention in medical students. In this three-arm randomized controlled trial, 160 Chinese medical students were randomized to one of three reading conditions: Original Text Group (OTG), AI-assisted Bilingual Group (ABG), or Full Translation Group (FTG). Immediate post-reading outcomes included intrinsic, extraneous, and germane cognitive load, as well as comprehension performance. One-week delayed productive vocabulary retention was assessed using a prespecified scoring rubric. Group differences were analyzed using analysis of covariance (ANCOVA) adjusted for academic year and CET-6 level. A total of 148 participants completed the immediate post-reading assessment, and 148 completed the one-week follow-up according to the available dataset. Compared with the OTG and ABG, the FTG showed significantly higher extraneous cognitive load (both p < 0.001). Immediate comprehension scores were high across groups and did not differ significantly (p = 0.157). Delayed productive vocabulary retention differed significantly among groups, with the highest mean score in the OTG (6.38 ± 2.13), followed by the ABG (5.58 ± 1.89) and FTG (4.90 ± 2.00) (overall p < 0.001). Post-hoc analyses showed that the OTG outperformed both the ABG (p = 0.011) and FTG (p < 0.001). Among Chinese medical students reading an English biomedical article, full translation was associated with higher perceived extraneous cognitive load and weaker one-week retention of methodological English vocabulary than direct reading of the original English text. A bilingual parallel-text format showed intermediate performance. These findings suggest that translation may be more appropriately used as a selective scaffold rather than a default substitute when the educational goal includes durable acquisition of English medical terminology.

Meibomian gland dysfunction (MGD) is the leading cause of evaporative dry eye disease and arises from failure of a coordinated molecular network that normally maintains meibomian gland homeostasis. In health, endocrine-lipidogenic signaling via peroxisome proliferator-activated receptor-γ (PPARγ) and androgen receptor (AR), trophic pathways such as epidermal growth factor and Hedgehog, a circadian-metabolic axis coupling nicotinamide adenine dinucleotide (NAD+)-dependent steroidogenesis to lipid output, and neuroimmune circuits involving Toll-like receptors and nuclear factor-κB (NF-κB) act together to regulate stem/progenitor maintenance, meibocyte differentiation and lipid secretion. In MGD these axes become progressively uncoupled: hormonal and metabolic stress reduce NAD+ and intracrine androgen production, dampening AR-PPARγ activity; loss of trophic support exhausts basal progenitor pools; and chronic NF-κB-driven inflammation with Th17 and interleukin-33 (IL-33) signaling promotes ductal hyperkeratinization, acinar loss and fibrosis. Lipidomic studies show a shift from cholesteryl esters (CEs) toward free fatty acids, along with remodeling of O-acyl-ω-hydroxy fatty acid (OAHFA) profiles, oxidized lipids and eicosanoids, which stiffen meibum, destabilize the tear film lipid layer and fuel inflammation. Recent single-cell and organoid studies further map cellular heterogeneity and disease-linked lineage changes. Biomarkers such as cholesteryl ester/wax ester ratios, OAHFA profiles, eicosanoids, cytokines and imaging metrics offer read-outs of axis-specific dysfunction. Therapeutically, emerging strategies seek to correct these defects by enhancing AR-PPARγ signaling and NAD+-dependent steroidogenesis, re-engaging trophic pathways, normalizing ductal keratinization with "soft" keratolytics and inhibiting inflammatory circuits. This review integrates these mechanisms, disease networks, biomarker signatures and interventions into a unified model to support mechanism-based, biomarker guided precision care in MGD.

The objective of this study was to investigate whether eyeliner use is associated with an increase in dry eye symptoms. A survey was conducted to collect data on cosmetic usage and Ocular Surface Disease Index (OSDI) scores from a diverse public sample. Additionally, eyecare professionals were queried regarding their practice of inquiring about cosmetic use during patient consultations. The survey included specific questions about eyeliner application and the calculation of OSDI scores, with a score of 13 or higher indicating the presence of dry eye symptoms. Individuals who reported using eyeliner had a significantly higher rate of OSDI scores above 13 compared to non-users (42.93% vs. 33.38%, p < 0.001). Notably, subjects who applied eyeliner to the lid margins exhibited an even more pronounced increase in high OSDI scores (48.17%, p < 0.001). Furthermore, a significant proportion of patients (23.37%) expressed reluctance to discontinue cosmetic use when advised in medical contexts, while only 48.19% of healthcare providers routinely inquired about cosmetic use during patient consultations. The usage of eyeliner is associated with higher OSDI scores, underscoring the need for both eyecare practitioners and eyeliner users to be more cognizant of the potential impact of eyeliner on the ocular surface.

Purpose:This study aims to explore the effects of Chinese acupoint eye exercises on ocular vascular parameters and to understand its role in modulating blood flow dynamics after near-vision tasks. Methods:Fifty-five participants (110 eyes) from September through November 2023 randomized to four groups: the standard Chinese acupoint eye exercise group (SCAEE), sham acupoint eye exercise group (SAEE), simply eye closure group, and simply distance looking group (SDL). Ocular parameters, including retinal and choroidal thickness, perfusion area, and vessel density, were measured using Swept-source Optical Coherence Tomography. The impact of these exercises was evaluated through paired samples t-tests. Results:All groups experienced an overall increase in retinal thickness, except for the SDL group. Significant thickening of the retinal nerve fiber layer was observed in SCAEE group, and SDL group. However, the outer retina layer showed the most significant thinning in SDL group. The perfusion area displayed a decrease in deep vascular perfusion and an increase in superficial vascular perfusion area in SCAEE group and SAEE group. All interventions showed an immediate decrease in choroidal thickness, with the SCAEE group and the SAEE group showing significant increases after a longer period. Conclusions:Periocular acupressure showed a direct, instant, and continuing impact on retinal thickness, choroidal thickness, perfusion area, and vascular density. Translational Relevance:Our findings demonstrate that periocular acupressure induces significant changes in ocular vascular parameters after near-vision tasks, suggesting its potential role of alleviating accommodative stress and thus contribute to delaying myopia onset in high-risk populations.

This digest summarizes the interdisciplinary research in dry eye disease (DED) published since the 2017 TFOS DEWS II reports. It comprises 7 topics including Sex, Gender, and Hormones; Epidemiology; Pathophysiology; Tear Film; Pain and Sensation; Iatrogenic Dry Eye; and Clinical Trial Design and explores how each of these inform diagnostic methodology, disease subtype, and management of DED. Sex- and gender-related differences significantly influence the ocular surface due to hormones, sex chromosomes, sex-specific autosomal factors, epigenetics, care-seeking behaviors, and service use. Epidemiologic data reveal that DED prevalence varies by age and sex, influenced by diagnostic criteria and the multifactorial nature of the disease. New risk factors for DED include environmental, iatrogenicity, systemic diseases, and lifestyle domains. Pathophysiological distinctions between aqueous deficient and more evaporative forms of DED have been clarified, with the latter most commonly characterized by a muted inflammatory response at the ocular surface, meibomian gland dysfunction, and conceivably phenotypic changes in corneal epithelial cells. There is an expanding role for metabolic, hormonal, physical, neural and cellular stresses, including hyperosmolarity, mitochondrial stress, and neurogenic inflammation. Advancements in tear film research recommend new approaches to understanding DED pathogenesis and identifying biomarkers, such as microRNAs. Ocular pain perception is linked to structural integrity of corneal nerves, functional capacities of neurons, and activity of the central and peripheral nervous systems. Iatrogenic DED can result from medications, contact lenses, and surgical procedures. Clinical trials now emphasize aligning design and end points with DED subtypes and therapeutic mechanisms, with new therapeutics and trial designs under consideration.

STING (stimulator of interferon genes) is involved in viral and bacterial defense through interferon pathway and innate immunity. Increased susceptibility to infection is a common manifestation of multiple myeloma (MM). Thus, we aimed to explore the clinical significance and possible mechanism of STING in MM. Immunohistochemistry and qPCR were used to detect STING expression in the bone marrow of MM patients, and flow cytometry was used to detect the amount of intracellular STING. All data were analyzed with clinical characteristics. STING expression was remarkably reduced in MM tissues compared to normal tissues and was not associated with stage. Multivariate analysis identified STING as an independent prognostic factor in MM patients (P = 0.001). In the bortezomib-containing regimens, patients with low STING expression were more difficult to achieve remission. A model incorporating STING and m-SMART significantly improved the predictive accuracy of overall survival in bortezomib regimens (AUC, 0.511 to 0.630, P = 0.044). Bortezomib efficacy has been reported to correlate with activated immunity, but the low expression group manifested as immune apathy. Although baseline characteristics showed intergroup differences in infection, the low expression group had an increased proportion of bacterial infections (1.7-fold) and a prolonged duration of antibiotic/antifungal medication (3.55 additional days); these patients were accompanied by a decreased neutrophil-to-lymphocyte ratio (NLR) and rarely activated neutrophils and leukocytes. The intracellular STING ratio was also defective in neutrophil-dominated leukocytes. Our study revealed that STING had a strong association with bortezomib and could serve as a potential target for immunotherapy in multiple myeloma.

INTRODUCTION:The aim of the study was to investigate the anterior segment anatomical parameters associated with the scleral spur and cornea for risk profiling of primary angle closure glaucoma (PACG). METHODS:A retrospective study was conducted, collecting parametric measurements obtained using CASIA 2 and IOLMaster 700. Univariate and multivariate logistic regression models were utilized to compare ocular parameters between the narrow angle (NA) group and PACG group, as well as identify risk factors for PACG. The predictive performance of each parameter was evaluated using the area under the receiver operating characteristic (AUROC) curve. RESULTS:A total of 84 patients with PACG (48 with PACG and 36 with chronic PACG) and 84 patients with NA were included in this study. In the multivariable model, it was demonstrated that individuals with a smaller trabecular scleral-spur angle (TSA: OR = 0.810, per 1° increase, p < 0.001, AUROC = 0.738) and larger relative lens vault (rLV: OR = 1.112, per 1 percent increase, p < 0.001, AUROC = 0.720) had an increased risk of developing PACG. Furthermore, combining TSA with rLV yielded an improved AUROC value of 0.807 (p < 0.001). CONCLUSION:AS-OCT is a valuable tool for early assessment of progression risk in NA patients at risk for developing PACG. Our findings suggest that both TSA and rLV are significant risk factors for PACG. Moreover, the novel parameter TSA demonstrates promising potential as a predictive tool for early PACG screening.

Exposure to particulate matters in air pollution of 2.5 μm or less (PM2.5) was associated with loss of meibomian glands. The aim of this study was to verify that PM2.5 could directly impact meibomian gland epithelial cells and damage their function. To investigate the impact of PM2.5 on meibomian gland, immortalized human meibomian gland epithelial cells were treated with various concentrations of PM2.5 in vitro. Meibomian gland cell microstructure, cell viability, expression of proliferating cell nuclear antigen and IL-1β, and intracellular accumulation of acidic vesicles were measured by transmission electron microscopy, cell counting, western blot and LysoTracker staining, respectively. To further study the effect of PM2.5 in vivo, male C57BL/6J mice were treated with 5mg/ml PM2.5 or vehicle for 3 months. Corneal fluorescein staining and ocular examinations were done before and after the treatment. Eyelids tissues were processed for morphological studies, immunostaining and Oil Red O staining. Our data suggest that exposure to PM2.5 caused significant meibomian gland dropout, clogged gland orifice and increased corneal fluorescein staining that were consistent with the clinical presentations of meibomian gland dysfunction. Prominent changes in the morphology and ultrastructure of meibomian glands was observed with PM2.5 treatment. PM2.5 promoted ductal keratinization, inhibited cell proliferation, induced cell apoptosis and increased Interleukin-1β production in meibomian gland epithelial cells. This study may explain the association between PM2.5 exposure and meibomian gland dropout observed in clinic. PM2.5 resuspension instillation could be used to induce a meibomian gland dysfunction animal model.

OBJECTIVE:To determine whether fibroblast growth factor receptor (FGFR)-targeting drug could impact human meibomian gland.METHODS:We followed up with three patients who were using pemigatinib for 4 to 10 weeks. The patients were evaluated for their ocular surface disease index, best-corrected visual acuity, Schirmer test, cornea staining, meibum expressibility score, tear meniscus height, noninvasive tear film breakup time, and meibomian gland area. The distribution of the FGFR family, FGF7, and FGF10 were evaluated by immunofluorescence staining and Western blot in fresh tarsal tissues from deidentified patients who underwent lid plastic surgeries.RESULTS:All patients developed apparent meibomian gland atrophy, shortening and narrowing of ducts, and significantly increased meibum expressibility and decreased noninvasive tear film breakup time within 5 to 8 weeks. Laboratory evaluations confirmed that human meibomian gland expresses abundant fibroblast growth factor receptors.CONCLUSIONS:These findings indicate that meibomian gland is a target tissue of FGFR inhibitors, and patients who use these drugs may develop meibomian gland dysfunction.

Aihua Yu, Yang Liu This large scar on the right cornea of a patient in their 50s is due to herpes zoster ophthalmicus (fig 1). The previous year the patient had shingles on the right side of their face and over the subsequent year developed a painless, progressive clouding in the right cornea. Clinical examination on presentation showed severe impairment of corneal sensation in the right eye. Visual acuity was 20/20 in both eyes as the scar spared the visual axis. Corneal confocal microscopy, a non-invasive imaging technique, confirmed nerve loss to the cornea. Herpes zoster ophthalmicus may present with conjunctivitis, keratitis, or uveitis.1 The infection is more common in older people and thosewith immunosuppression, and it can result in blindness if the central cornea is scarred.1 -3

Meibomian gland dysfunction (MGD) is a functional and morphological disorder of the meibomian glands which results in qualitative or quantitative alteration in meibum secretion and is the major cause of evaporative dry eye (EDE). EDE is often characterized by tear film instability, increased evaporation, hyperosmolarity, inflammation, and ocular surface disorder. The precise pathogenesis of MGD remains elusive. It has been widely considered that MGD develops as a result of ductal epithelial hyperkeratinization, which obstructs the meibomian orifice, halts meibum secretion, and causes secondary acinar atrophy and gland dropout. Abnormal self-renewal and differentiation of the acinar cells also play a significant role in MGD. This review summarizes the latest research findings regarding the possible pathogenesis of MGD and provides further treatment strategies for MGD-EDE patients.

This study aimed to compare the utility of four different dyes for intracellular lipid detection in immortalized human meibomian gland epithelial cells (IHMGECs). IHMGECs were cultured in a serum-containing medium for 10 days in the presence or absence of Roxadustat (Roxa), a known inducer of IHMGEC differentiation. Cells were then fixed and stained with Oil Red O (ORO), Sudan III (SIII), LipidTOX green (LT), or Nile Red (NR). IHMGECs were evaluated for the number, size, and area of stained intracellular lipid vesicles or the intensity of staining using bright field (ORO, SIII) or fluorescence (LT, NR) microscopy. Data were captured with ImageJ and analyzed with Student's two-tailed t-test. Our findings demonstrate that different staining methods can yield significantly different patterns of intracellular lipid quantity and/or distribution in IHMGECs. ORO and SIII significantly increased the size and area of lipid-containing vesicles in Roxa-treated cells. Neither stain showed a change in the number of vesicles during IHMGEC differentiation. Vesicle size was significantly greater in cells stained with ORO, as compared to SIII. In addtion, LT, but not NR, showed a significant increase in intracellular lipid intensity in IHMGECs following Roxa -induced differentiation. Our results demonstrate significant differences in the distribution patterns and intensities of lipid-containing vesicles in IHMGECs after staining with ORO, SIII, LT, and NR. ORO, SIII, and LT, but not NR staining, are helpful methods to help identify and quantitate the extent of intracellular lipid accumulation during IHMGEC differentiation.

We aim to assess the effects of different air pollutants on meibomian gland dysfunction (MGD). As a prospective multicenter study, 864 patients were recruited from four different regions (i.e., coal, oil, steel, and living). The oil region had a significantly lower temperature and higher O 3 and SO 2 concentrations than other regions. Notably, participants in oil region presented with more frequent and serious MGD signs and higher cytokine levels (median interleukin 6 [IL-6] in oil: 2.66, steel: 0.96, coal: 0.38, living: 0.56; IL-8 in oil: 117.52, steel: 46.94, coal: 26.89, living: 33; vascular endothelial growth factor [VEGF] in oil: 25.09, steel: 14.02, coal: 14.02, living: 28.47). The short-term fluctuations of cytokine levels were associated with the changes in gas levels (PM 2.5 and IL-8: β = 0.016 [0.004–0.029]; O 3 and IL-6: β = 0.576 [0.386–0.702]; O 3 and IL-8: β = 0.479 [0.369–0.890]; SO 2 and VEGF: β = 0.021 [0.001–0.047]). After long-term exposure, lid margin neovascularization (r = 0.402), meibomian gland (MG) expression (r = 0.377), MG secretion (r = 0.303), MG loss (r = 0.404), and tear meniscus height (r = − 0.345) were moderately correlated with air quality index (AQI). Individuals in oil region had more serious MGD signs and higher cytokine levels. MGD is susceptible to long-term exposure to high AQI.

PurposeTo assess air pollution-induced changes on ocular surface and tear cytokine levels.MethodsAs a prospective multicenter cohort study, 387 dry eye disease (DED) participants were recruited from five provinces in China and underwent measurements of ocular surface disease index (OSDI), Schirmer’s I test (ST), tear meniscus height (TMH), tear film break-up time (TBUT), corneal fluorescein staining (CFS), meibomian gland (MG) function, and tear cytokines. The associations between ocular surface parameters and exposure to particulate matter (PM), ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2) for 1 day, 1 week, and 1 month before the examination were analyzed in single- and multi-pollutant models adjusted for confounding factors.ResultsIn the multi-pollutant model, the OSDI score was positively correlated with PM with diameter ≤2.5 μm (PM2.5), O3, and SO2 exposure [PM2.5: β (1 week/month) = 0.229 (95% confidence interval (CI): 0.035–0.424)/0.211 (95% CI: 0.160–0.583); O3: β (1 day/week/month) = 0.403 (95% CI: 0.229–0.523)/0.471 (95% CI: 0.252–0.693)/0.468 (95% CI: 0.215–0.732); SO2: β (1 day/week) = 0.437 (95% CI: 0.193–0.680)/0.470 (95% CI: 0.040–0.901)]. Tear secretion was negatively correlated with O3 and NO2 exposures but positively correlated with PM2.5 levels. Air pollutants were negatively correlated with TBUT and positively related with CFS score. Besides SO2, all other pollutants were associated with aggravated MG dysfunction (MG expression, secretion, and loss) and tear cytokines increasement, such as PM2.5 and interleukin-8 (IL-8) [β (1 day) = 0.016 (95% CI: 0.003–0.029)], PM with diameter ≤10 μm (PM10) and IL-6 [β (1 day) = 0.019 (95% CI: 0.006–0.033)], NO2 and IL-6 [β (1 month) = 0.045 (95% CI: 0.018–0.072)], among others. The effects of air pollutants on DED symptoms/signs, MG functions and tear cytokines peaked within 1 week, 1 month, and 1 day, respectively.ConclusionIncreased PM2.5, O3, and SO2 exposures caused ocular discomfort and damage with tear film instability. PM10 exposure led to tear film instability and ocular injury. PM, O3, and NO2 exposures aggravated MG dysfunction and upregulated tear cytokine levels. Therefore, each air pollutant may influence DED via different mechanisms within different time windows.

Purpose Extracellular matrix (ECM) is a key component of the stem cell local microenvironment. Our study aims to explore the periglandular distribution of major components of ECM in the Meibomian gland (MG). Methods Human eyelids and mouse eyelids were collected and processed for immunofluorescence staining. Results Human MG tissues stained positive for collagen IV α1, collagen IV α2, collagen IV α5, and collagen IV α6 around the acini and duct, but negative for collagen IV α3 and collagen IV α4. The mouse MG were stained positive for the same collagen IV subunits as early as postnatal day 15. Laminin α2, laminin β1 and perlecan stained the regions surrounding the acini and the acinar/ductal junction in the human MG, but not the region around the duct. Tenascin-C was found specifically located at the junctions between the acini and the central ducts. Neither agrin nor endostatin was found in the human MG tissues. Conclusion The ECM expresses specific components in different regions around the MG, which may play a role in MG stem cell regulation, renewal, and regeneration.

We recently discovered that by changing environmental signals, differentiated immortalized human meibomian gland epithelial cells (IHMGECs) de-differentiate into proliferating cells. We also discovered that following exposure to appropriate stimuli, these proliferative cells re-differentiate into differentiated IHMGECs. We hypothesize that this plasticity of differentiated and proliferative IHMGECs is paralleled by very significant alterations in cellular gene expression. To begin to test this hypothesis, we compared the gene expression patterns of IHMGECs during differentiation and proliferation. IHMGECs were cultured for four days in either differentiating or proliferating media. After four days of culture, cells were processed for the analysis of gene expression by using Illumina BeadChips and bioinformatic software. Our study identified significant differences in the expression of more than 9200 genes in differentiated and proliferative IHMGECs. Differentiation was associated with significant increases in the expression of specific genes (e.g. S100 calcium binding protein P; 7,194,386-fold upregulation) and numerous ontologies (e.g. 83 biological process [bp] ontologies with ≥100 genes were upregulated), such as those related to development, transport and lysosomes. Proliferation also led to a significant rise in specific gene expressions (e.g. cathelicidin antimicrobial peptide; 859,100-fold upregulation) and many ontologies (115 biological process [bp] ontologies with ≥100 genes were upregulated), with most of the highly significant ontologies related to cell cycle (z scores > 13.9). Our findings demonstrate that gene expression in differentiated and proliferative IHMGECs is extremely different. These results may have significant implications for the regeneration of HMGECs and the reversal of MG dropout in MG dysfunction.

Purpose We recently discovered that a hypoxic environment is beneficial for meibomian gland (MG) function. The mechanisms underlying this effect are unknown, but we hypothesize that it is due to an increase in the levels of hypoxia-inducible factor 1α (HIF1α). In other tissues, HIF1α is the primary regulator of cellular responses to hypoxia, and HIF1α expression can be induced by multiple stimuli, including hypoxia and hypoxia-mimetic agents. The objective of this study was to test our hypothesis. Methods Human eyelid tissues were stained for HIF1α. Immortalized human MG epithelial cells (IHMGECs) were cultured for varying time periods under normoxic (21% O2) or hypoxic (1% O2) conditions, in the presence or absence of the hypoxia-mimetic agent roxadustat (Roxa). IHMGECs were then processed for the analysis of cell number, HIF1α expression, lipid-containing vesicles, neutral and polar lipid content, DNase II activity, and intracellular pH. Results Our results show that HIF1α protein is present in human MG acinar epithelial cells in vivo. Our findings also demonstrate that exposure to 1% O2 or to Roxa increases the expression of HIF1α, the number of lipid-containing vesicles, the content of neutral lipids, and the activity of DNase II and decreases the pH in IHMGECs in vitro. Conclusions Our data support our hypothesis that the beneficial effect of hypoxia on the MG is mediated through an increased expression of HIF1α.