PURPOSE:To investigate the effect of corneal flap margin space width after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) on corneal nerve regeneration using in vivo confocal microscopy (IVCM). METHODS:This study assessed 46 consecutive patients who underwent FS-LASIK surgery. Routine examinations after myopic laser surgery were performed. IVCM was performed before and after surgery to observe the flap margin space and regeneration of the corneal subbasal nerve. The average of corneal flap margin space was calculated. Patients were divided into two groups: the wide-space group (> 20 µm) and the narrow-space group (⩽ 20 µm). Central and peripheral (average of 3-, 6-, and 9-o'clock positions) corneal sensitivity was tested by the Cochet-Bonnet esthesiometer and corneal subbasal nerve regeneration was quantitatively analyzed. RESULTS:Postoperatively at days 1 to 90, the incision edge of the narrow-space group showed a high-density linear structure without obvious epithelial cells filling in the space, and the corneal nerve gradually grew from the outside of the flap through the incision edge to the inside of the flap. In the wide-space group, obvious epithelial cells filling in the space were observed from 1 day postoperatively, and the corneal nerve grew less from the outside of the flap through the incision edge to the inside of the flap. There was no significant intergroup difference in the central corneal nerve fiber length. However, the peripheral corneal nerve fiber length in the narrow-space group was significantly higher at both 30 and 90 days postoperatively. No statistically significant differences were observed between groups in central and peripheral corneal sensitivity. There was no significant difference in spherical equivalent between groups at each time point. CONCLUSIONS:Although the postoperative flap margin space significantly affects corneal nerve regeneration, it does not influence corneal sensitivity or the refractive outcome after FS-LASIK.

To develop a deep-learning model capable of measuring essential anterior segment (AS) parameters derived from preoperative ultrasound biomicroscopy (UBM) images of candidates for implantable collamer lens (ICL) surgery. Tianjin Medical University Eye Hospital, Tianjin, China. Cross-sectional retrospective study. A dataset comprising 1,480 preoperative panoramic UBM images taken from 638 eyes of 320 subjects was collected and was divided into training and testing subsets at a proportion of 7:3. Using the YOLOv8-pose algorithm, the model identified ten anatomical key point coordinates and computed six relevant AS parameters. Both manual and anterior segment optical coherence tomography-based non-contact measurements served as reference standards for evaluating the model’s accuracy. The relationship between postoperative vault and preoperative parameters measured by the model was analyzed using multiple linear regression. On the test dataset, the model achieved an intraclass correlation coefficient (ICC) exceeding 0.978, with a mean Euclidean distance of 67.65 ± 54.25 μm across all point locations. The ICC values for anterior chamber depth (ACD), pupil diameter, and sulcus-to-sulcus distance were above 0.980 (95

PURPOSE:To evaluate the efficacy and safety of a single Tearmaestro® liquid pulsation treatment for meibomian gland dysfunction (MGD)-related dry eye disease. METHODS:In this prospective trial, 31 patients with MGD-related dry eye received a single 12-minute treatment. The primary outcome was the change in the Ocular Surface Disease Index (OSDI) score from baseline to the 1-month follow-up. Secondary outcomes included tear film break-up time (TBUT), corneal fluorescein staining (CFS), lipid layer thickness (LLT), meibomian gland secretion (MGS) and orifice (MQS) scores, Schirmer I test, tear meniscus height (TMH), and safety parameters. All measures were assessed at baseline, 7 days, 1 month, and 3 months. RESULTS:The primary outcome, demonstrated a significant reduction at 1 month (p < 0.0001), with improvements sustained at all follow-ups (all p < 0.0001). Key secondary outcomes also showed significant improvement: TBUT increased at 1 and 3 months (p < 0.05), and CFS improved at 3 months (p < 0.0001). Significant enhancements in LLT, MQS, and MGS were observed at 1 and/or 3 months (all p < 0.01). LLT positively correlated with TBUT (p < 0.01) and negatively with CFS (p < 0.05). No serious adverse events occurred. CONCLUSION:A single Tearmaestro® liquid pulsation treatment significantly improves the primary outcome of patient-reported symptoms at 1 month, with concurrent benefits in tear film stability and meibomian gland function lasting up to 3 months. The treatment demonstrated a favorable safety profile, offering an efficient clinical option for MGD-related dry eye.

Corneal nerve mosaics enable comprehensive observation and quantitative analysis for early neurological disease assessment. However, rigid-alignment-based stitching of in vivo confocal microscopy (IVCM) images often introduces geometric discontinuities and fiber breakages at seams. We propose NerveStitcher3.0, a fully automatic stitching method that combines robust rigid alignment to establish the global panorama with a VoxelMorph-based non-rigid module confined to the overlap. The framework first employs our prior NerveStitcher to estimate translation and construct a panoramic canvas, then learns dense deformation fields to locally correct geometric discrepancies and nerve misalignments without altering the global layout. Validated on 15 IVCM image sets, NerveStitcher3.0 improves nerve-fiber continuity and seam smoothness over rigid baselines while preserving global geometric consistency and maintaining compatibility with existing clinical pipelines.

Purpose: To investigate the expression and role of translocator protein (TSPO) in dry eye disease (DED). Methods: In vitro experiments were performed using immortalized human corneal epithelial cells (HCECs) cultured under hyperosmolar conditions (500 mOsM). Cell viability was analyzed by the Cell Counting Kit-8 assay. Intracellular reactive oxygen species (ROS) generation was detected by 2 ',7 '-dichlorodihydrofluorescein diacetate staining. Mitochondrial membrane potential was assessed using the JC-1 assay. Intracellular calcium (Ca2+) levels were measured by Fluo-4 AM staining. Apoptosis was analyzed by flow cytometry. Mitochondrial morphology was observed using transmission electron microscopy. mRNA expression was quantified by real-time PCR. Protein expression was assessed by western blotting, enzyme-linked immunosorbent assay, and immunofluorescence. In vivo experiments were conducted using a scopolamine-induced DED model in female Wistar rats. Clinical parameters of tear secretion, corneal epithelium defects, and conjunctival goblet cells density were measured. mRNA and protein expression in the cornea and conjunctiva were assessed by real-time PCR, western blotting, and immunofluorescence. Apoptosis in the cornea and conjunctiva was assessed by TUNEL staining. Results: In vitro, TSPO was overexpressed in HCECs exposed to hyperosmotic stress, accompanied by elevated levels of pro-inflammatory cytokines, ROS overproduction, intracellular Ca2+ overload, and mitochondrial dysfunction, ultimately leading to apoptosis. TSPO knockdown significantly enhanced cell survival by attenuating these cellular injuries and inhibiting apoptosis via a mitochondria-dependent pathway. In vivo, increased TSPO expression was observed in both the corneal and conjunctival tissues of DED rats, along with elevated inflammation. Treatment with the TSPO-specific ligand PK11195 significantly antagonized TSPO expression, alleviated inflammation, preserved corneal epithelial integrity, and suppressed apoptosis without reversing tear deficiency. Conclusions: TSPO overexpression participates in the pathogenesis of DED. Inhibiting TSPO alleviates inflammation and oxidative stress and promotes cell survival through a mitochondrial-dependent pathway.

AIM: To compare the efficacy, safety, visual outcomes, satisfaction, and comfort of three-dimensional (3D) heads-up visualization system-assisted and conventional microscopic implantable Collamer lens (ICL) surgery. METHODS: Patients undergoing ICL or Toric ICL (TICL) implantation were enrolled and randomized into two groups: TM group (under a conventional microscope) and 3DM group (under NGENUITY 3D visualization system). Ocular parameters were assessed preoperatively and at 1wk, 1, 3, and 6mo postoperatively. The duration of key surgical steps and the incidence of complications were recorded. Patient-reported outcomes (dry eye, visual quality, comfort) and surgeon satisfaction were assessed using standardized questionnaires. RESULTS: The study included 98 eyes of 98 refractive error patients (17 males), 50 eyes in TM group (age 27.74±5.65y), and 48 eyes in 3DM group (age 29.20±4.89y). Efficacy, safety, quality of vision (QoV), dry eye symptoms, and patients' satisfaction at 6mo were not significant across the time points of 1wk, 1, 3 and 6mo. No complication was observed in either group. The 3DM group was associated with a longer main step operation time (P=0.037) but better patient visual comfort (P<0.001). The difference in surgical fluency was not statistically significant (P=0.067). Notably, surgeons reported no delays or discomfort and rated the 3DM system significantly higher in image resolution, range of view, depth perception, color contrast, and postural comfort (all P<0.001). CONCLUSION: For ICL surgery, the use of the NGENUITY 3D visualization system achieves comparable surgical efficacy, safety, and patient satisfaction to procedures performed under a traditional microscope, while delivering superior intraoperative visual performance and postural comfort for the surgeon. These ergonomic and visual advantages make it a promising tool for enhancing clinical practice and surgical training.

The mitochondrial translocator protein (TSPO) is critically involved in the regulation of inflammatory responses. However, the specific functions and molecular mechanisms of TSPO in the pathogenesis of dry eye disease (DED) remain unclear. This study aims to investigate whether TSPO regulates the inflammatory response in an in vitro hyperosmolar model via the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway and to explore their relationship. The research employed a hyperosmolar-stressed human corneal epithelial cell (HCE-T) model and utilized various techniques, including Western blotting, quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), and immunofluorescence for comprehensive analysis. The results indicate that knocking down TSPO under hyperosmolar stimulation conditions significantly increased PPARγ expression levels while stabilizing mitochondrial membrane potential. Mechanistic studies revealed that further knockdown of PPARγ following hyperosmolar stimulation and TSPO knockdown led to upregulation of TSPO expression and exacerbated cell apoptosis. This finding suggests that PPARγ may exert feedback regulatory effects on TSPO. The observed phenotypic reversal after gene knockdown suggests that TSPO may influence cellular inflammatory responses and apoptosis via the mitochondrial pathway through regulation of PPARγ. In conclusion, this study's findings indicate that mutual regulation between TSPO and PPARγ may constitute an important signaling pathway in the inflammatory response associated with DED. The dynamic balance within this pathway may contribute to maintaining homeostasis in corneal epithelial cells. Based on the current in vitro findings, these insights enhance our understanding of the pathogenesis underlying dry eye and suggest potential targets for developing new treatment strategies.

Aggregation-induced emission (AIE)-active fluorescent probes have emerged as promising tools for in vivo biomarker detection and biological imaging due to their unconventional emission behavior in aggregated state. In this study, we designed novel imidazole-based aggregation-induced emission luminogens (AIEgens), TPIT, featuring a symmetrical donor-π-bridge-acceptor-π-bridge-donor (D-π-A-π-D) backbone. By introducing benzothiadiazole (BT)-derived acceptors with different electron-withdrawing capabilities and steric hindrance, a series of AIEgens (TPIT-B, TPIT-P, TPIT-N) were successfully synthesized, exhibiting tunable emission windows from red (641 nm) to near-infrared (NIR) region (802 nm), typical AIE characteristics, significant Stokes shifts (> 120 nm ) and remarkable reactive oxygen species (ROS) generation efficiency. In further animal experiments, TPIT-N nanoparticles (NPs) achieved high-contrast NIR imaging of osteosarcoma (OS) tissues. Our preliminary findings reveal that the optical performance of TPIT can be facilely modulated to meet specific requirements by rational selection of acceptor cores. This flexible molecular engineering strategy endows TPIT with board potential in medical diagnostics, tumor treatments and other biological applications.

This study aimed to investigate the therapeutic potential and anti-inflammatory mechanisms of tacrolimus (FK506) in moderate to severe dry eye by clinical, in vivo, and in vitro studies. We evaluated the effect of 0.1 % FK506 versus 0.1 % fluorometholone eye drops on patients with moderate to severe dry eye. Ocular surface disease index questionnaire (OSDI), tear breakup time (TBUT), corneal erosion, Schirmer's I test, and conjunctival impression cytology were measured at 2, 4, and 8 weeks. Tear samples from patients before and after FK506 treatment were subjected to proteomic analysis. The underlying mechanisms of FK506 were clarified using dry eye rat model and hypertonic-stimulated human corneal epithelial cells. Results demonstrated that FK506 showed transiently superior efficacy over fluorometholone in OSDI at week 2 (P = 0.041) and TBUT at week 4 (P = 0.001), despite both groups achieving significant improvements in all parameters from baseline to week 8 (P < 0.001). Tear proteomics revealed FK506-mediated modulation of autophagy-lysosomal pathway. FK506 improved ocular surface damage, reduced TNF-α and IL-1β, and upregulated LC3B II, TFEB, and LAMP1 protein expression, accompanied by reduced P62 in the rat cornea. In vitro, FK506 suppressed pro-inflammatory cytokines via enhanced autophagic flux, promoted TFEB nuclear translocation, restored lysosomal structural and functional integrity, while inhibited mTOR phosphorylation. Knockdown of TFEB reversed the FK506-mediated benefits. Overall, FK506 alleviates the symptoms and signs of moderate to severe dry eye by suppressing the inflammatory response in corneal epithelial cells. This therapeutic effect is mediated through the activation of the TFEB-driven autophagy-lysosomal pathway.

To investigate the corneal epithelial remodeling profile after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK) for high myopia, as well as its possible consequence for subjective and objective changes in visual quality. This prospective observational study included 72 eyes with high myopia, divided into two groups, who underwent either SMILE or FS-LASIK. In addition to standard evaluation, anterior segment optical coherence tomography was used to assess central 6-mm corneal epithelial thickness (ET) before surgery and at 1 week, 1, 3, and 6 months after surgery; ET inhomogeneity across the central 5- and 6-mm cornea was quantified using the coefficient of variance (CV). The objective optical quality includes the modulation transfer function cut off frequency (MTF cut off), Strehl ratio, objective scatter index (OSI), and mean OSI obtained using the Optical Quality Analysis System-II. Patient-reported quality of vision was determined with a modified National Eye Institute Refractive Error Quality of Life questionnaire. The correlation of postoperative ET and treatment parameters with visual quality related parameters was analyzed. Both ET and CV were significantly increased in the SMILE and FS-LASIK groups at 6 months postoperatively (P < 0.001). Paracentral ET was positively correlated with changes in MTF cut off and Strehl ratio at 1 week after SMILE (0.338, 0.405, separately, P < 0.05). For FS-LASIK, ET was negatively correlated with MTF cut off change at 1, 3, 6 months postoperatively (-0.334, -0.385, -0.375, separately, P < 0.05); Central 6-mm CV and Strehl ratio significant correlated at 6 months (-0.427, P = 0.01); ET was significantly correlated with patient-reported quality of vision (P < 0.05). No correlation was found between preoperative spherical equivalent, keratometry values, total corneal thickness, optical zone, and ablation depth and changes in visual quality parameters. Correction of high myopia with SMILE and FS-LASIK induced epithelial remodeling involved an increase in ET and ET inhomogeneity. Epithelial changes in different regions have different effects on subjective and objective visual quality, which may have a certain clinical relevance of the corneal epithelial thickness measurement for visual quality assessment after refractive surgery.

AIM: To compare the efficacy of 3% diquafosol sodium (DQS) eye drops at different frequencies in dry eye (DE) after femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: In this prospective study, DE patients after FS-LASIK were randomly divided into two groups. All patients were administered routine anti-inflammatory and anti-infective drugs after FS-LASIK. Additionally, both groups were treated with DQS, at frequencies of 4 (DQS4 group) and 6 (DQS6 group) times daily. Corneal fluorescein staining (CFS) score, non-invasive tear breakup time (NIBUT), tear meniscus height (TMH), lipid layer thickness (LLT), and incomplete blink rate (IBR) were assessed in patients preoperatively and at 1wk, 1, and 3mo postoperatively. The Ocular Surface Disease Index (OSDI) questionnaire was also administered. RESULTS: Totally 119 patients (238 eyes) were randomly divided into the DQS4 group (60 individuals with 120 eyes) and DQS6 group (59 individuals with 118 eyes). From 1wk to 1mo after FS-LASIK, the CFS score in the DQS6 group decreased with statistical significance (P=0.014), while the DQS4 group showed an upward trend. Comparing with preoperative values, the NIBUT of both groups was significantly prolonged at various time points after FS-LASIK (P<0.05). Within 1mo post FS-LASIK, both groups had significantly higher OSDI scores compared with preoperative values (P<0.05). At postoperative 3mo, the DQS4 group recovered to a level similar to that before surgery (P>0.05), while the DQS6 group remained a little higher than preoperative values (P>0.05). The TMH levels in the DQS4 group increased significantly at 1wk postoperatively (P<0.05), while there was no statistically significant change in the TMH levels in the DQS6 group (P>0.05). There was no significant difference in IBR and LLT between the two groups within 1mo postoperatively. At postoperative 3mo, the LLT in the DQS4 group was significantly higher than that in the DQS6 group (P<0.05). CONCLUSION: Within 1mo post-FS-LASIK, applying DQS six times daily is superior to four daily applications in improving CFS score, and in increasing NIBUT meanwhile. After 1mo, applying DQS four times daily also effectively alleviate DE symptoms and improve DE signs. Therefore, we recommend DE patients using DQS eye drops 6 times daily within 1mo after FS-LASIK, and maintaining it 4 times daily until 3mo postoperatively.

Accurate prediction of postoperative vault height following implantable collamer lens (ICL) V4c implantation is critical for minimizing complications and achieving optimal surgical outcomes. This study aims to evaluate the performance of machine learning models in predicting postoperative vault height, focusing on both regression and classification approaches. This retrospective study analyzed biometric and demographic data, including anterior chamber depth, white-to-white distance, and ICL size, among other variables. Regression and classification models were developed using gradient boosting, random forest, and CatBoost algorithms. Regression models predicted vault height as a continuous variable, while classification models categorized vault heights into binary and multi-class tasks. Model performance was evaluated using metrics including the mean absolute error (MAE) and root mean squared error (RMSE) for regression models, while accuracy, F1-score, and area under the curve (AUC) were used for classification models. Regression models demonstrated moderate predictive performance, with random forest delivering the best performance (MAE: 134.0 µm, RMSE: 171.3 µm, Pearson’s correlation coefficient: 0.45). On the other hand, classification models exhibited greater clinical applicability than regression approaches. For the binary classification task (vault < 250 µm vs. ≥ 250 µm), gradient boosting achieved the highest overall performance, with accuracy of 89 ± 12

Background:Quantitative assessment of corneal epithelial thickness (CET) has attracted a great attention for its wide application in refractive surgeries. The corneal nerves are crucial for epithelial homeostasis, and nerve injury due to corneal refractive surgery may affect the epithelia; however, few clinical studies have investigated this relationship. Our study aimed to observe changes in epithelial thickness and sub-basal nerve plexus (SNP) profile after small incision lenticule extraction (SMILE) for low-to-moderate myopia [spherical refraction of -6.0 to 0 diopters (D)], and investigate the relationship between them. Methods:This prospective observational study included 52 eyes treated with SMILE from March to May 2023 at Tianjin Medical University Eye Hospital. The epithelial thickness was measured across the central and concentric (paracentral, mid-peripheral, and peripheral) regions using spectral-domain optical coherence tomography (SD-OCT). SNPs were observed in the central and peripheral (temporal, superior, nasal, and inferior) areas using in vivo confocal microscopy (IVCM), and seven nerve parameters were assessed. All eyes were examined preoperatively and 1 week, 1 month, and 6 months postoperatively. Pearson's correlation was employed to investigate the association between anterior Q-value (corneal asphericity) and epithelial thickness. Partial correlation was adopted to examine the relationship between epithelial thickness and corresponding nerve parameters. Results:Both epithelial thickness and SNP exhibited changes after SMILE. Six months postoperatively, epithelial thickness in the central and paracentral regions increased (all P<0.05), with thickening particularly pronounced in the inferotemporal, temporal, and inferior sections of the paracentral region, and the anterior Q-value was positively correlated with epithelial thickness in the inferonasal, inferior, and inferotemporal sections (inferonasal section: r=0.293, P=0.035; inferior section: r=0.396, P=0.004; inferotemporal section: r=0.374, P=0.006). Furthermore, most central, superior, and nasal nerve parameters had still not reached preoperative levels, while most temporal and inferior nerve parameters had reached or exceeded preoperative levels, and epithelial thickness was positively correlated with corresponding nerve parameters [corneal nerve fiber density (CNFD): r=0.171, P=0.006; corneal nerve branch density (CNBD): r=0.137, P=0.028; corneal nerve fiber length (CNFL): r=0.172, P=0.006; corneal nerve fiber total branch density (CNTB): r=0.141, P=0.024; corneal nerve fiber area (CNFA): r=0.164, P=0.008]. Conclusions:Uneven epithelial thickness changes were observed after SMILE, regional epithelial thickening increased corneal oblateness. Non-uniform SNP regeneration was also observed, positive correlation between epithelial thickness and nerve parameters indicated the impact of nerves on epithelia, which may enhance the clinical value of epithelial thickness measurement.

PURPOSE:To evaluate the expression differences of tear lymphotoxin-α (LT-α), total immunoglobulin E (IgE), and matrix metalloproteinase-9 (MMP-9) in seasonal/perennial allergic conjunctivitis-associated dry eye (S/PAC-DE) and their clinical relevance, probing the underlying pathogenesis of S/PAC-DE. METHODS:This study enrolled 37 S/PAC-DE patients, 23 dry eye (DE) patients, and 24 healthy controls (HC). Assessing the clinical parameters, tear LT-α, total IgE, MMP-9, and nine other inflammatory cytokines in the three groups. Correlations between tear cytokines and clinical parameters were also analyzed. RESULTS:Tear LT-α levels were significantly lower in S/PAC-DE compared to DE and HC groups. Tear total IgE, TNF-α, and MMP-9 levels were significantly upregulated in the S/PAC-DE group than those in the DE (all p < 0.001) and HC groups (p = 0.005, p < 0.001, and p = 0.048). In the S/PAC-DE group, total IgE was positively correlated with MMP-9 (r = 0.652, p = 0.008). Total IgE and LT-α were positively correlated in the DE group (r = 0.498, p = 0.016), while the two showed a negative correlation trend in the S/PAC-DE group (r=-0.272, p = 0.103). LT-α was positively correlated with tear film break-up time and negatively correlated with corneal fluorescein staining score in both the S/PAC-DE and DE groups. CONCLUSIONS:In the S/PAC-DE co-morbid state, the inhibition of tear LT-α expression and the upregulation of the pro-inflammatory cytokines total IgE, TNF-α, and MMP-9 may collectively contribute to the disruption of the ocular surface epithelial barrier, further promoting and exacerbating DE. Additionally, the differences in correlation between LT-α and total IgE in the S/PAC-DE and common DE patients may be related to the distinct ocular immune microenvironments.

ObjectivesTo investigate the clinical characteristics and the expression of mucin 5AC (MUC5AC) in in diabetic and non-diabetic subjects with or without dry eye disease.MethodsA total of 399 participants (796 eyes) aged 50-80 years were enrolled in this study. Participants were divided into 4 groups: non-diabetic without dry eye group (normal group), non-diabetic with dry eye group, diabetic without dry eye group and diabetic with dry eye group. Demographic information, fasting plasma glucose (FBG), and glycated haemoglobin A1C (HbA1C) data were collected. Additionally, ocular surface disease index (OSDI) questionnaire, signs of dry eye, tear osmolarity, and meibomian glands were evaluated. Tear MUC5AC expression and conjunctival goblet cells density (GCD) were tested.ResultsCompared with non-diabetic with dry eye group, diabetic with dry eye group showed significantly lower tear film osmolarity (TFO), but higher corneal fluorescein and conjunctival lissamine green staining scores. In comparison with diabetic without dry eye group, diabetic with dry eye group showed significantly higher TFO, corneal fluorescein and conjunctival lissamine green staining scorers. The MUC5AC concentration and GCD of diabetic with dry eye group was significantly lower than those of the non-diabetic with dry eye group. Diabetic subjects with higher HbA1c levels (>= 7.8%) showed higher TFO and shorter fluorescein tear break time.ConclusionDiabetics with dry eye exhibited notably higher corneal fluorescein and conjunctival lissamine green staining scores. Conjunctival goblet cells and MUC5AC were significantly reduced in diabetics. Higher TFO was associated with the duration of diabetes and HbA1c levels.

Acute lung injury (ALI) is a common postoperative complication, particularly in pediatric patients after liver transplantation. Hepatic ischemia–reperfusion (HIR) increases the release of exosomes (IR-Exos) in peripheral circulation. However, the role of IR-Exos in the pathogenesis of ALI induced by HIR remains unclear. Here, we explored the role of exosomes derived from the HIR-injured liver in ALI development. Intravenous injection of IR-Exos caused lung inflammation in naive rats, whereas pretreatment with an inhibitor of exosomal secretion (GW4869) attenuated HIR-related lung injury. In vivo and in vitro results show that IR-Exos promoted proinflammatory responses and M1 macrophage polarization. Furthermore, miRNA profiling of serum identified miR-122-5p as the exosomal miRNA with the highest increase in young rats with HIR compared with controls. Additionally, IR-Exos transferred miR-122-5p to macrophages and promoted proinflammatory responses and M1 phenotype polarization by targeting suppressor of cytokine signaling protein 1(SOCS-1)/nuclear factor (NF)-κB. Importantly, the pathological role of exosomal miR-122-5p in initiating lung inflammation was reversed by inhibition of miR-122-5p. Clinically, high levels of miR-122-5p were found in serum and correlated to the severity of lung injury in pediatric living-donor liver transplant recipients with ALI. Taken together, our findings reveal that IR-Exos transfer liver-specific miR-122-5p to alveolar macrophages and elicit ALI by inducing M1 macrophage polarization via the SOCS-1/NF-κB signaling pathway.

To explore the efficacy and relevant mechanism of 0.05% cyclosporine A (CsA) eye drops (II) monotherapy in patients with allergic conjunctivitis-associated dry eye (ACDE). Prospective, randomized, controlled study. Fifty-three patients with mild-to-moderate ACDE were randomly assigned to two groups. The CsA group received 0.05% CsA eye drops (II) monotherapy four times daily. The control group received 0.1% olopatadine twice daily combined with 0.1% preservative-free artificial tears four times daily. Clinical symptoms and signs, tear total IgE, and lymphotoxin-α (LT-α) concentrations were assessed at pre- and post-treatment days 7, 30, and 60. And we further measured six tear cytokines levels using a microsphere-based immunoassay. The CsA group showed significant improvement in symptoms (Ocular Surface Disease Index and itching scores) and signs (conjunctival hyperaemia, conjunctival oedema, conjunctival papillae, tear break-up time (TBUT), corneal fluorescein staining, and goblet cell density) at each follow-up period compared to pre-treatment (all P < 0.050). And its improvement in itching scores (P7th < 0.001, P30th = 0.039, and P60th = 0.031) and TBUT (P7th = 0.009, P30th = 0.003, and P60th = 0.005) was more significant than the control group at all follow-up periods. The tear total IgE, interleukin (IL)-5, IL-6, periostin, eotaxin-3, and MMP-9 levels significantly decreased in the CsA group at day 60 after treatment (all P < 0.050). And the changed values in tear total IgE were positively correlated with the change in itching scores. 0.05% CsA eye drops (II) monotherapy can rapidly improve the symptoms and signs, especially in ocular itching and TBUT, in patients with ACDE. And its efficacy is superior to 0.1% olopatadine combined with artificial tears. Moreover, CsA downregulates the expression levels of tear inflammatory cytokines, including tear total IgE, IL-5, IL-6, periostin, eotaxin-3, and MMP-9. Among that, the reduction in tear total IgE levels may reflect the improvement of ocular itching.

Radiotherapy (RT) is a crucial treatment for colorectal cancer (CRC) patients, but it often fails to induce systemic antitumor immunity. CD73, an immunomodulatory factor, is upregulated after RT and associated with poor prognosis in CRC patients. This study aims to elucidate the mechanisms driving RT-induced CD73 upregulation in CRC and investigate how combining RT with CD73 blockade stimulates immune responses and induces abscopal effects. Findings revealed that RT-induced CD73 upregulation is mediated by the ataxia telangiectasia and Rad3-related (ATR) pathway and correlated with RT tolerance, as demonstrated through flow cytometry, immunofluorescence, and Western Blotting. Using flow cytometry and multicolor immunofluorescence, experiments demonstrated that in CRC subcutaneous tumor models, combination therapy reduces the infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and regulatory T cells (Tregs) while increasing dendritic cells (DCs) and CD8 + T cells, resulting in superior antitumor responses. Additionally, results from flow cytometry, Western Blot, and RNA sequencing demonstrated that combination therapy enhances the antigen-presenting ability of DCs and activates tumor antigen-specific CD8 + T cells, improving their function and delaying their depletion. The activation of the cGAS-STING and IFN-I pathways is crucial for this effect. In summary, the integration of RT with CD73 blockade effectively reverses the immunosuppressive TME and invigorates CD8 + T cell-driven, specific antitumor immune responses. These insights shed fresh light on the mechanisms governing the synergistic modulation of immunity by RT and CD73 blockade in CRC, offering promising avenues for the advancement of therapeutic strategies against CRC.

We examined the effects of climatic factors and Demodex infestations on meibomian gland dysfunction (MGD)-associated dry eye disease (DED) in a cross-sectional study. This study included 123 patients from Tianjin and Chengdu regions, and climate factors and the Air Quality Index (AQI) were recorded for one year. Ocular surface parameters and Demodex infestations were evaluated using various tests. Significant differences in all climatic factors and AQI were observed between Tianjin and Chengdu (P < 0.01), and ocular surface parameters also differed significantly between the two regions (P < 0.05). Temperature, relative humidity, and precipitation positively correlated with tear break-up time (BUT), meibum gland expressibility, and lid margin irregularity but negatively correlated with lissamine green staining scores (P < 0.05). Wind speed and atmospheric pressure positively correlated with corneal fluorescein staining and lissamine green staining but negatively correlated with BUT and lid margin irregularity (P < 0.05). AQI positively correlated with DED symptoms and corneal findings but negatively correlated with tear film stability and meibomian gland characteristics (P < 0.05). Demodex infestation was only positively correlated with meibum quality scores (P < 0.05). Our findings suggest that geographic climates influence ocular surface characteristics in MGD-associated DED, with daily precipitation potentially playing a significant role, and Demodex infestation contributes to meibum gland degeneration.

A cross-sectional population-based survey in the Beichen district of Tianjin was conducted to estimate the prevalence of dry eye disease (DED) among the population over 50 years old with Dry Eye Workshop (DEWS) II and Chinese expert consensus (CEC) criteria. A total of 5791 subjects over 50 years old were enrolled. Ocular surface disease index (OSDI) questionnaire, lipid layer thickness (LLT), partial blink ratio (PBR), fluorescein tear film breakup time (FBUT), Schirmer I test (SIT), fluorescein staining, meibomian gland dropout, meibomian gland expression scores (MES) and quantity scores (MQS) was assessed. Additionally, basic information, weight, disease history, living habits, anxiety, and depression condition were collected. According to the CEC, the prevalence of DED was 39.0