A novel image deep learning-based sub-centimeter pulmonary nodule management algorithm to expedite resection of the malignant and avoid over-diagnosis of the benign.

OBJECTIVES: With the popularization of chest computed tomography (CT) screening, there are more sub-centimeter (≤ 1 cm) pulmonary nodules (SCPNs) requiring further diagnostic workup. This area represents an important opportunity to optimize the SCPN management algorithm avoiding "one-size fits all" approach. One critical problem is how to learn the discriminative multi-view characteristics and the unique context of each SCPN. METHODS: Here, we propose a multi-view coupled self-attention module (MVCS) to capture the global spatial context of the CT image through modeling the association order of space and dimension. Compared with existing self-attention methods, MVCS uses less memory consumption and computational complexity, unearths dimension correlations that previous methods have not found, and is easy to integrate with other frameworks. RESULTS: In total, a public dataset LUNA16 from LIDC-IDRI, 1319 SCPNs from 1069 patients presenting to a major referral center, and 160 SCPNs from 137 patients from three other major centers were analyzed to pre-train, train, and validate the model. Experimental results showed that performance outperforms the state-of-the-art models in terms of accuracy and stability and is comparable to that of human experts in classifying precancerous lesions and invasive adenocarcinoma. We also provide a fusion MVCS network (MVCSN) by combining the CT image with the clinical characteristics and radiographic features of patients. CONCLUSION: This tool may ultimately aid in expediting resection of the malignant SCPNs and avoid over-diagnosis of the benign ones, resulting in improved management outcomes. CLINICAL RELEVANCE STATEMENT: In the diagnosis of sub-centimeter lung adenocarcinoma, fusion MVCSN can help doctors improve work efficiency and guide their treatment decisions to a certain extent. KEY POINTS: • Advances in computed tomography (CT) not only increase the number of nodules detected, but also the nodules that are identified are smaller, such as sub-centimeter pulmonary nodules (SCPNs). • We propose a multi-view coupled self-attention module (MVCS), which could model spatial and dimensional correlations sequentially for learning global spatial contexts, which is better than other attention mechanisms. • MVCS uses fewer huge memory consumption and computational complexity than the existing self-attention methods when dealing with 3D medical image data. Additionally, it reaches promising accuracy for SCPNs' malignancy evaluation and has lower training cost than other models.

Expression Changes in Programmed Death Ligand 1 from Precancerous Lesions to Invasive Adenocarcinoma in Subcentimeter Pulmonary Nodules: A Large Study of 2022 Cases in China.

PURPOSE: This large-scale, multicenter, retrospective observational study aimed to evaluate the clinicopathological and molecular profiles associated with programmed death-ligand 1 (PD-L1) expression in precancerous lesions and invasive adenocarcinoma in subcentimeter pulmonary nodules. PATIENTS AND METHODS: Patients with histologically confirmed atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (ADC) were included. PD-L1 expression was evaluated at each center using a PD-L1 immunohistochemistry 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). The tumor proportion score (TPS) cutoff values were set at ≥ 1% and ≥ 50%. RESULTS: A total of 2022 nodules from 1844 patients were analyzed. Of these, 9 (0.45%) nodules had PD-L1 TPS ≥ 50%, 187 (9.25%) had PD-L1 TPS 1-49%, and 1826 (90.30%) had PD-L1 TPS < 1%. A total of 378 (18.69%), 1016 (50.25%), and 628 (31.06%) nodules were diagnosed as AAH/AIS, MIA, and ADC, respectively, by pathology. A total of 1377 (68.10%), 591 (25.67%), and 54 (2.67%) nodules were diagnosed as pure ground-glass opacity (GGO), mixed GGO, and solid nodules, respectively, by computed tomography. There was a significant difference between PD-L1 expression and anaplastic lymphoma kinase (ALK) mutation status (P < 0.001). PD-L1 expression levels were significantly different from those determined using the International Association for the Study of Lung Cancer (IASLC) grading system (P < 0.001). CONCLUSIONS: PD-L1 expression was significantly associated with radiological and pathological invasiveness and driver mutation status in subcentimeter pulmonary nodules. The significance of PD-L1 expression in the evolution of early-stage lung adenocarcinoma requires further investigation.

A yes-associated protein 1- Notch1 receptor positive feedback loop promotes breast cancer lung metastasis by attenuating the bone morphogenetic protein 4-SMAD family member 1/5 signaling.

The Notch1 (Notch1 receptor) and yes-associated protein 1 (YAP1) signaling can regulate breast cancer metastasis. This study aimed at investigating whether and how these two signal pathways crosstalk to promote breast cancer lung metastasis. Here, we show that YAP1 expression was positively correlated with Notch1 in breast cancer according to bioinformatics and experimental validation. Mechanistically, YAP1 with TEA domain transcription factors (TEADs) enhanced Jagged1(JAG1)-Notch1 signaling. Meanwhile, Notch1 promoted YAP1 stability in breast cancer cells by inhibiting the ß-TrCP-mediated degradation, thereby, forming a YAP1- JAG1/Notch1 positive feedback loop in breast cancer. Furthermore, YAP1 enhanced the mammosphere formation and stemness of MDA-MB-231 cells by attenuating the inhibition of the BMP4-SMAD1/5 signaling. In vivo, the YAP1- JAG1/Notch1 positive feedback loop promoted the lung colonization of MDA-MB-231 cells. Our data for the first time indicate that the YAP1-Notch1 positive feedback loop promotes lung metastasis of breast cancer by modulating self-renewal and inhibiting the BMP4-SMAD1/5 signaling.

Deep Phenotyping of Chinese Electronic Health Records by Recognizing Linguistic Patterns of Phenotypic Narratives With a Sequence Motif Discovery Tool: Algorithm Development and Validation.

BACKGROUND: Phenotype information in electronic health records (EHRs) is mainly recorded in unstructured free text, which cannot be directly used for clinical research. EHR-based deep-phenotyping methods can structure phenotype information in EHRs with high fidelity, making it the focus of medical informatics. However, developing a deep-phenotyping method for non-English EHRs (ie, Chinese EHRs) is challenging. Although numerous EHR resources exist in China, fine-grained annotation data that are suitable for developing deep-phenotyping methods are limited. It is challenging to develop a deep-phenotyping method for Chinese EHRs in such a low-resource scenario. OBJECTIVE: In this study, we aimed to develop a deep-phenotyping method with good generalization ability for Chinese EHRs based on limited fine-grained annotation data. METHODS: The core of the methodology was to identify linguistic patterns of phenotype descriptions in Chinese EHRs with a sequence motif discovery tool and perform deep phenotyping of Chinese EHRs by recognizing linguistic patterns in free text. Specifically, 1000 Chinese EHRs were manually annotated based on a fine-grained information model, PhenoSSU (Semantic Structured Unit of Phenotypes). The annotation data set was randomly divided into a training set (n=700, 70%) and a testing set (n=300, 30%). The process for mining linguistic patterns was divided into three steps. First, free text in the training set was encoded as single-letter sequences (P: phenotype, A: attribute). Second, a biological sequence analysis tool-MEME (Multiple Expectation Maximums for Motif Elicitation)-was used to identify motifs in the single-letter sequences. Finally, the identified motifs were reduced to a series of regular expressions representing linguistic patterns of PhenoSSU instances in Chinese EHRs. Based on the discovered linguistic patterns, we developed a deep-phenotyping method for Chinese EHRs, including a deep learning-based method for named entity recognition and a pattern recognition-based method for attribute prediction. RESULTS: In total, 51 sequence motifs with statistical significance were mined from 700 Chinese EHRs in the training set and were combined into six regular expressions. It was found that these six regular expressions could be learned from a mean of 134 (SD 9.7) annotated EHRs in the training set. The deep-phenotyping algorithm for Chinese EHRs could recognize PhenoSSU instances with an overall accuracy of 0.844 on the test set. For the subtask of entity recognition, the algorithm achieved an F1 score of 0.898 with the Bidirectional Encoder Representations from Transformers-bidirectional long short-term memory and conditional random field model; for the subtask of attribute prediction, the algorithm achieved a weighted accuracy of 0.940 with the linguistic pattern-based method. CONCLUSIONS: We developed a simple but effective strategy to perform deep phenotyping of Chinese EHRs with limited fine-grained annotation data. Our work will promote the second use of Chinese EHRs and give inspiration to other non-English-speaking countries.

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis.

Airway epithelial apoptosis and epithelial mesenchymal transition (EMT) are two crucial components of asthma pathogenesis, concomitantly mediated by TGF-ß1. RACK1 is the downstream target gene of TGF-ß1 shown to enhancement in asthma mice in our previous study. Balb/c mice were sensitized twice and challenged with OVA every day for 7 days. Transformed human bronchial epithelial cells, BEAS-2B cells were cultured and exposed to recombinant soluble human TGF-ß1 to induced apoptosis (30 ng/mL, 72 hours) and EMT (10 ng/mL, 48 hours) in vitro, respectively. siRNA and pharmacological inhibitors were used to evaluate the regulation of RACK1 protein in apoptosis and EMT. Western blotting analysis and immunostaining were used to detect the protein expressions in vivo and in vitro. Our data showed that RACK1 protein levels were significantly increased in OVA-challenged mice, as well as TGF-ß1-induced apoptosis and EMT of BEAS-2B cells. Knockdown of RACK1 (siRACK1) significantly inhibited apoptosis and decreased TGF-ß1 up-regulated EMT related protein levels (N-cadherin and Snail) in vitro via suppression of JNK and Smad3 activation. Moreover, siSmad3 or siJNK impaired TGF-ß1-induced N-cadherin and Snail up-regulation in vitro. Importantly, JNK gene silencing (siERK) also impaired the regulatory effect of TGF-ß1 on Smad3 activation. Our present data demonstrate that RACK1 is a concomitant regulator of TGF-ß1 induces airway apoptosis and EMT via JNK/Smad/Snail signalling axis. Our findings may provide a new insight into understanding the regulation mechanism of RACK1 in asthma pathogenesis.

Latent membrane protein 2A inhibits expression level of Smad2 through regulating miR-155-5p in EBV-associated gastric cancer cell lines.

Epstein-Barr virus (EBV) infection is one of the causes of gastric cancer (GC). Besides, previous studies have demonstrated that EBV-encoded latent membrane protein 2A (LMP2A) influences the pathogenesis of EBV-associated gastric cancer (EBVaGC) through regulating several key pathways. In this study, the expression level of Smad2 was observed, which was reduced in EBVaGC cell lines, especially in the presence of LMP2A. Meanwhile, we found that LMP2A promoted the expression of miR-155-5p by activated nuclear factor-κB (NF-κB) signaling. After being treated with NF-κB inhibitor (BAY 11-7082), miR-155-5p sharply decreased. Western blot analysis proved that the overexpression of miR-155-5p could inhibit Smad2. Functional studies showed that the role of miR-155-5p might lead to good prognosis in EBV-positive GC through promoting cell apoptosis and cell cycle arrest, as well as inhibiting tumor proliferation. In addition, p-Smad2 protein was also reduced or induced by overexpression or knockdown, respectively, of miR-155-5p. Immunofluorescence analysis further indicated that LMP2A prevented p-Smad2 from transferring to the nucleus, which played a crucial role in transforming growth factor-ß (TGF-ß) signaling. In summary, our findings confirmed the relationship between LMP2A and Smad2 and provided a potential regulation of the TGF-ß pathway in EBVaGC.

A hybrid CNN feature model for pulmonary nodule malignancy risk differentiation.

The malignancy risk differentiation of pulmonary nodule is one of the most challenge tasks of computer-aided diagnosis (CADx). Most recently reported CADx methods or schemes based on texture and shape estimation have shown relatively satisfactory on differentiating the risk level of malignancy among the nodules detected in lung cancer screening. However, the existing CADx schemes tend to detect and analyze characteristics of pulmonary nodules from a statistical perspective according to local features only. Enlightened by the currently prevailing learning ability of convolutional neural network (CNN), which simulates human neural network for target recognition and our previously research on texture features, we present a hybrid model that takes into consideration of both global and local features for pulmonary nodule differentiation using the largest public database founded by the Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI). By comparing three types of CNN models in which two of them were newly proposed by us, we observed that the multi-channel CNN model yielded the best discrimination in capacity of differentiating malignancy risk of the nodules based on the projection of distributions of extracted features. Moreover, CADx scheme using the new multi-channel CNN model outperformed our previously developed CADx scheme using the 3D texture feature analysis method, which increased the computed area under a receiver operating characteristic curve (AUC) from 0.9441 to 0.9702.

SwinUNet: a multiscale feature learning approach to cardiovascular magnetic resonance parametric mapping for myocardial tissue characterization.

Objective.Cardiovascular magnetic resonance (CMR) can measure T1 and T2 relaxation times for myocardial tissue characterization. However, the CMR procedure for T1/T2 parametric mapping is time-consuming, making it challenging to scan heart patients routinely in clinical practice. This study aims to accelerate CMR parametric mapping with deep learning.Approach. A deep-learning model, SwinUNet, was developed to accelerate T1/T2 mapping. SwinUNet used a convolutional UNet and a Swin transformer to form a hierarchical 3D computation structure, allowing for analyzing CMR images spatially and temporally with multiscale feature learning. A comparative study was conducted between SwinUNet and an existing deep-learning model, MyoMapNet, which only used temporal analysis for parametric mapping. The T1/T2 mapping performance was evaluated globally using mean absolute error (MAE) and structural similarity index measure (SSIM). The clinical T1/T2 indices for characterizing the left-ventricle myocardial walls were also calculated and evaluated using correlation and Bland-Altman analysis.Main results. We performed accelerated T1 mapping with ≤4 heartbeats and T2 mapping with 2 heartbeats in reference to the clinical standard, which required 11 heartbeats for T1 mapping and 3 heartbeats for T2 mapping. SwinUNet performed well in all the experiments (MAE < 50 ms, SSIM > 0.8, correlation > 0.75, and Bland-Altman agreement limits < 100 ms for T1 mapping; MAE < 1 ms, SSIM > 0.9, correlation > 0.95, and Bland-Altman agreement limits < 1.5 ms for T2 mapping). When the maximal acceleration was used (2 heartbeats), SwinUNet outperformed MyoMapNet and gave measurement accuracy similar to the clinical standard.Significance. SwinUNet offers an optimal solution to CMR parametric mapping for assessing myocardial diseases quantitatively in clinical cardiology.

Management of Glaucoma-Related Dry Eye Disease with Intense Pulsed Light: A Randomized Control Study.

Purpose: The objective of this study was to assess the effectiveness of intense pulsed light (IPL) therapy in individuals diagnosed with glaucoma and dry eye disease (DED). Methods: This randomized control study recruited 22 individuals diagnosed with glaucoma, ranging in age from 33 to 82 years. These participants were undergoing treatment with hypotensive eyedrops and had clinical indications and subjective complaints associated with dry eye. Each patient underwent three sessions of IPL therapy in one eye, while the contralateral eye served as the control eye (CT). The following parameters were assessed at three time points: baseline, week-2, and week-4. These parameters include non-invasive breakup time (NITBUT), tear meniscus height (TMH), conjunctivocorneal epithelial staining score (CS), tear film lipid layer (TFLL), meibomian gland expressibility score (MGEx), Schirmer I test, ocular bulbar redness score (OBRS), and ocular surface disease index (OSDI). Intraocular pressure (IOP), best-corrected visual acuity (BCVA), and corneal endothelial cell count (ECC) were assessed for safety. The clinical trial was registered on 25/12/2023 at ClinicalTrials.gov website (NCT06158984). Results: Comparing baseline and 4-week measurements revealed that the IPL group found significant improvements in NITBUT (IPL: 8.74±2.60 sec. vs CT: 5.76±1.75 sec. p<0.01), TMH (IPL: 0.23±0.05mm vs CT: 0.19±0.06mm, p=0.011), C.S. (IPL: 1.14±0.56 vs CT: 1.95±1.17, p=0.005), TFLL (IPL: 2.91±2.91 vs CT:3.36±0.58, p=0.047), MGEx score (IPL: 1.14±0.35 vs CT: 1.45±0.51, p=0.020) and OSDI scores (IPL: 31.77±15.59 vs 50.59±21.55, p=0.002) significantly improved. Conversely, other parameters showed no significant improvements (p>0.05). Conclusion: The progression of ocular surface disease in individuals using topical anti-glaucoma medication may worsen if the condition is not addressed. Nevertheless, IPL therapy has the potential to result in significant improvements in both objective and subjective measures of dry eye. Best-corrected visual acuity, endothelial cell count, and intraocular pressure were determined to be within the permitted limits. No adverse events were reported during the course of the study.

The results show that people who use topical medicines to treat glaucoma may get worse eye surface disease if they do not treat the problem. IPL treatment, on the other hand, can make a big difference in both objective and subjective dry eye tests. The vision, endothelial cell count, and the pressure inside the eye were all found to be within normal limits after the IPL treatment. Even though the people in our study had glaucoma and had been taking glaucoma medicine for it for a year and the fact that the symptoms last for a long time may also change the results. Also, DED caused by glaucoma medication is complicated, with a lot of different symptoms and signs, even in the same stage. Also, subjective complaints may not match up with clinical signs. The type, amount, and length of anti-glaucoma drugs may have affected the results.

Nomogram for Predicting Central Nervous System Infection Following Traumatic Brain Injury in the Elderly.

OBJECTIVE: This study aims to identify risk factors for central nervous system (CNS) infection in elderly patients hospitalized with traumatic brain injury (TBI) and to develop a reliable predictive tool for assessing the likelihood of CNS infection in this population. METHOD: We conducted a retrospective study on 742 elderly TBI patients treated at Tangdu Hospital, China. Clinical data was randomly split into training and validation sets (7:3 ratio). By conducting univariate and multivariate logistic regression analysis in the training set, we identified a list of variables to develop a nomogram for predicting the risk of CNS infection. We evaluated the performance of the predictive model in both cohorts respectively, using receiver operating characteristics curves, calibration curves, and decision curve analysis. RESULTS: Results of the logistic analysis in the training set indicated that surgical intervention (P = 0.007), red blood cell count (P = 0.019), C-reactive protein concentration (P < 0.001), and cerebrospinal fluid leakage (P < 0.001) significantly predicted the occurrence of CNS infection in elderly TBI patients. The model constructed based on these variables had high predictive capability (area under the curve-training = 0.832; area under the curve-validation = 0.824) as well as clinical utility. CONCLUSIONS: A nomogram constructed based on several key predictors reasonably predicts the risk of CNS infection in elderly TBI patients upon hospital admission. The model of the nanogram may contribute to timely interventions and improve health outcomes among affected individuals.

High-Q Thin-Film Lithium Niobate Microrings Fabricated with Wet Etching.

Thin-film lithium niobate (TFLN) has been widely used in electro-optic modulators, acoustic--optic modulators, electro-optic frequency combs, and nonlinear wavelength converters owing to the excellent optical properties of lithium niobate. The performance of these devices is highly dependent on the fabrication quality of TFLN. Although state-of-the-art TFLN microrings with an intrinsic quality factor (Q-factor) exceeding 1 × 107 have been realized by inductively coupled plasma-reactive ion etching (ICP-RIE) and chemical mechanical polishing (CMP), ICP-RIE has moderate throughput, moderate reproducibility, and high cost in etching TFLN, while CMP features moderate throughput and low cost in etching TFLN. Here, a wet etching method for TFLN, leading to the fabrication of a micro-racetrack with an intrinsic Q-factor of over 9.27 × 106 is developed. The suitability of this method to fabricate a narrow coupling gap between the bus waveguide and microring enables the coupling conditions of the microring to be customized. This method features a high throughput, a high reproducibility, and a low cost in etching TFLN, showing the potential to boost the mass production of integrated LN photonic devices with high fidelity and affordability dramatically.

TeaBERT: An Efficient Knowledge Infused Cross-Lingual Language Model for Mapping Chinese Medical Entities to the Unified Medical Language System.

Medical entity normalization is an important task for medical information processing. The Unified Medical Language System (UMLS), a well-developed medical terminology system, is crucial for medical entity normalization. However, the UMLS primarily consists of English medical terms. For languages other than English, such as Chinese, a significant challenge for normalizing medical entities is the lack of robust terminology systems. To address this issue, we propose a translation-enhancing training strategy that incorporates the translation and synonym knowledge of the UMLS into a language model using the contrastive learning approach. In this work, we proposed a cross-lingual pre-trained language model called TeaBERT, which can align synonymous Chinese and English medical entities across languages at the concept level. As the evaluation results showed, the TeaBERT language model outperformed previous cross-lingual language models with Acc@5 values of 92.54%, 87.14% and 84.77% on the ICD10-CN, CHPO and RealWorld-v2 datasets, respectively. It also achieved a new state-of-the-art cross-lingual entity mapping performance without fine-tuning. The translation-enhancing strategy is applicable to other languages that face the similar challenge due to the absence of well-developed medical terminology systems.

Mapping Chinese Medical Entities to the Unified Medical Language System.

Background: Chinese medical entities have not been organized comprehensively due to the lack of well-developed terminology systems, which poses a challenge to processing Chinese medical texts for fine-grained medical knowledge representation. To unify Chinese medical terminologies, mapping Chinese medical entities to their English counterparts in the Unified Medical Language System (UMLS) is an efficient solution. However, their mappings have not been investigated sufficiently in former research. In this study, we explore strategies for mapping Chinese medical entities to the UMLS and systematically evaluate the mapping performance. Methods: First, Chinese medical entities are translated to English using multiple web-based translation engines. Then, 3 mapping strategies are investigated: (a) string-based, (b) semantic-based, and (c) string and semantic similarity combined. In addition, cross-lingual pretrained language models are applied to map Chinese medical entities to UMLS concepts without translation. All of these strategies are evaluated on the ICD10-CN, Chinese Human Phenotype Ontology (CHPO), and RealWorld datasets. Results: The linear combination method based on the SapBERT and term frequency-inverse document frequency bag-of-words models perform the best on all evaluation datasets, with 91.85%, 82.44%, and 78.43% of the top 5 accuracies on the ICD10-CN, CHPO, and RealWorld datasets, respectively. Conclusions: In our study, we explore strategies for mapping Chinese medical entities to the UMLS and identify a satisfactory linear combination method. Our investigation will facilitate Chinese medical entity normalization and inspire research that focuses on Chinese medical ontology development.

Asymptomatic stones in the lacrimal canaliculus.

Key Clinical Message: Asymptomatic lacrimal canaliculus stones causing many stones without symptoms are rare. The patient recovered well within a week after dacryolith removal. This diagnosis is prevalent in this age group. However, asymptomatic nasolacrimal obstruction should be considered. Abstract: Dacryoliths, also known as symptomatic stones, are frequently observed in the lacrimal drainage system. These stones manifest through symptoms such as conjunctivitis, discharge, and epiphora. Nevertheless, the occurrence of numerous stones in the lacrimal canaliculus, in the absence of apparent symptoms, is uncommon. In this study, we present a case with the presence of several stones within the inferior lacrimal canaliculus. A female patient, aged 74, appeared with bilateral senile cataracts and was scheduled for cataract surgery. During a standard ocular examination, it was observed that the tear meniscus height in the left eye had a greater magnitude compared with the right eye. Canaliculitis with dacryolith was verified using a series of diagnostic procedures, including physical inspection, fluorescent dye disappearance test, palpation, 50 Mhz ultrasound biomicroscope scan, and irrigation of the lacrimal canaliculi. Upon surgical investigation, the canaliculus obstruction was confirmed, characterized by the existence of many tiny dacryolith formations inside the inferior canalicular system. Following the surgical excision of the dacryoliths, the patient experienced a full remission within a week. While it is common for individuals in this age range to receive this diagnosis, it is important to consider silent nasolacrimal blockage as a potential alternative diagnosis. It is important to note that the presence of dacryoliths in the lacrimal drainage system might manifest independently of conjunctivitis. No discernible risk indicators were found in relation to the aforementioned patient.

Protocol for a parallel assignment prospective, randomised, double-blinded, placebo-controlled trial to evaluate the efficacy of 0.01% atropine for near work-induced transient myopia and myopic progression in China.

INTRODUCTION: Assessment of near work-induced transient myopia (NITM) is important for permanent myopia development and progression. Atropine eye drop has been reported to be beneficial in reducing initial NITM and slowing down myopic progression. This study aimed to investigate the efficacy of 0.01% atropine in treating NITM and its possible association with the progression of refractive change in Chinese myopic children. METHODS AND ANALYSIS: The study is designed as a parallel assignment prospective, randomised, double-blinded, placebo-controlled trial conducted at He Eye Specialist Hospital in Shenyang, China. One hundred fifty participants will be randomly assigned in a 1:1 ratio to receive 0.01% atropine or placebo eye drop once nightly bilaterally for 1 year. Initial NITM, cycloplegic refraction, axial length, best-corrected visual acuity, intraocular pressure and pupil diameter will be measured at baseline, 4 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks. Visual Function Questionnaire will be administered at baseline and each follow-up visit. Adverse events also will be monitored and documented at each subsequent follow-up visit. ETHICS AND DISSEMINATION: A parallel assignment prospective, randomised, double-blinded, placebo-controlled trial to evaluate the efficacy of 0.01% atropine for near work-induced transient myopia and myopic progression registered on 10 September 2023. Ethics approval number: IRB (2023) K025.01. The study's findings will be shared regardless of the effect's direction. TRIAL REGISTRATION NUMBER: NCT06034366.

Protocol for a parallel assignment prospective, randomised, comparative trial to evaluate the safety and efficacy of intense pulsed light (IPL) combined with 3% diquafosol (DQS) ophthalmic solution in dry eye syndrome.

INTRODUCTION: Evaporative dry eye (EDE) is common and can lead to ocular pain, decreased visual quality and reduced quality of life. Intense pulsed light (IPL) and 3% diquafosol ophthalmic solution have been found to be beneficial in reducing signs and symptoms of dry eye. METHODS AND ANALYSIS: A randomised clinical trial will be performed at He Eye Specialist Hospital in Shenyang. 360 dry eye disease patients will be equally divided randomly into the IPL group, DQS group (3% diquafosol ophthalmic solution eye-drops) and IPL+group (IPL combined with 3% diquafosol eye-drops). All groups will be followed up for 4 weeks. The primary outcome measures will be the non-invasive tear break-up time and the Ocular Surface Disease Index change from the baseline. The secondary outcome measures willincludeconjunctival and cornea staining with fluorescein and lissamine, meibomian gland function and secretion quality, tear film lipid layer score, tear meniscus height, conjunctival hyperemia (redness score) changes . Adverse events also will be monitored and documented. DISCUSSION: This study aimed to assess whether the combination of IPL with 3% diquafosol ophthalmic solution (study group), IPL+ (study group), is more effective than IPL (active control group) or DQS (active control group) in participants with EDE. ETHICS AND DISSEMINATION: Management of dry eye with IPL combined with 3% diquafosol ophthalmic solution, registered on 23 January 2023. Ethics approval number: IRB (2022) K029.01. The study's findings will be shared regardless of the effect's direction. TRIAL REGISTRATION NUMBER: NCT05694026.

Tear Film Lipid Layer Changes Following Combined Effect of Heated Eye Mask with Intense Pulsed Light Therapy for Evaporative Dry Eye: A Randomized Control Study.

Background: Dry eye disease (DED) is a complex ocular surface inflammatory disorder with a multifactorial etiology. Therapies such as intense pulsed light (IPL) and heated eye mask (HEM) have been reported to improve the tear film lipid layer (TFLL) and signs and symptoms of DED. Methods: This randomized study aimed to compare the effects of IPL combined with HEM (IPL+HEM) group, IPL group, and control group in participants with evaporative DED. All participants were examined at baseline (D0), day 21 (D21), day 42 (D42), and day 84 (D84) for noninvasive tear breakup time (NITBUT), TFLL, corneal conjunctival staining (CS), meibomian gland quality (MGQ), meibomian gland expressibility (MGEx), and Ocular Surface Disease Index (OSDI). Results: The mean age of participants was IPL+HEM: 28.06 ± 3.88 years, IPL: 29.88 ± 4.68 years, and control: 28.52 ± 3.77 years. At D84, significant improvements in TFLL (p < 0.05), noninvasive tear breakup time (NITBUT) (p < 0.05), corneoconjunctival staining (CS) (p < 0.05), MGQ (p < 0.05), MGEx (p < 0.05), and OSDI (p < 0.05) were found in the IPL+HEM and IPL groups, whereas the control group had no significant improvements. Furthermore, ΔTFLL significantly correlated with ΔNITBUT (r = -0.678, p < 0.001), ΔCS (r = 0.321, p < 0.001), ΔMGQ (r = 0.669, p < 0.001), ΔMGEx (r = 0.598, p < 0.001), and ΔOSDI score (r = 0.649, p < 0.001). Conclusions: IPL therapy in combination with HEM and IPL therapy only can significantly improve the quality of TFLL and clinically reduce the sign and symptoms of evaporative DED. However, IPL therapy in combination with HEM was found to be more effective than IPL therapy alone.

Relationship between ocular surface pain and corneal nerve loss in dry eye diabetics: a cross-sectional study in Shenyang, China.

BACKGROUND: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED pathology. OBJECTIVE: To investigate the potential relationship between corneal nerve loss and ocular pain among diabetic patients with dry eye (DE). DESIGN: A cross-sectional study. SETTING: He Eye Specialist Hospital, Shenyang, China. PARTICIPANTS: This study recruited 124 eyes of 62 diabetic patients diagnosed with DED between August and October 2022. MAIN OUTCOME MEASURES: Best-corrected visual acuity, intraocular pressure, non-invasive tear breakup time, tear meniscus height, tear film lipid layer, conjunctival hyperaemia (redness score), conjunctivocorneal epithelial staining (CS score), central corneal sensitivity and vitro confocal corneal microscopy was assessed in all subjects. The Ocular Surface Disease Index Questionnaire assessed DE symptoms and ocular pain. RESULTS: The study's final analysis included 26 patients (52 eyes) without ocular pain and 36 patients (72 eyes) with ocular pain. The corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL) in patients with ocular pain were significantly lower than those without (p<0.001, p=0.004, and p<0.001, respectively). CNFD, CNBD and CNFL negatively correlated with ocular pain (r=-0.385, r=-0.260, r=-0.358, respectively). Moreover, CNFD, CNBD and CNFL have a significant (p<0.05) positive correlation with corneal sensitivity (r=0.523, r=0.330, r=0.421, respectively). CONCLUSIONS: Corneal nerve loss was associated with ocular pain and decreased corneal sensitivity in diabetic patients with DE. Further studies into the neurological role of ocular surface diseases can elaborate diagnostics, prognosis and treatment of diabetic patients with DE. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05193331).

The Combined Impact of Intense Pulsed Light Combined and 3% Diquafosol Ophthalmic Solution on Evaporative Dry Eye: A Randomized Control Study.

INTRODUCTION: The primary objective of this study is to assess whether the combination of intense pulsed light (IPL) with 3% diquafosol (DQS) ophthalmic solution is more effective than intense pulsed light in alleviating signs and symptoms of dry eye disease (DED). METHODS: This randomized study included 66 participants with evaporative dry eye (EDE) who received IPL + DQS therapy (n = 44 eyes), IPL therapy (n = 44 eyes), or sham therapy (n = 44 eyes). All participants were examined at baseline (D0), day 14 (D14), and day 28 (D28) for non-invasive break-up time (NITBUT), tear-film lipid layer (TFLL), corneal conjunctival staining (CS), meibomian gland quality (MGQ), meibomian gland expression (MGEx), and ocular surface disease index (OSDI). RESULTS: At day 28, comparison among the IPL + DQS therapy, IPL therapy, and sham therapy found significant differences in the mean NITBUT (12.03 ± 1.27 versus 10.47 ± 3.48 versus 4.57 ± 0.46; p < 0.001), TFLL (2.09 ± 0.29 versus 2.27 ± 0.45 versus 2.89 ± 0.65; p < 0.001), CS (1.43 ± 0.82 versus 1.93 ± 1.32 versus 3.52 ± 1.00; p < 0.001), MGQ (1.55 ± 0.66 versus 1.91 ± 0.77 versus 2.66 ± 0.53; p < 0.001), MGEx (1.27 ± 0.45 versus 1.75 ± 0.44 versus 2.41 ± 0.50; p < 0.001), and OSDI score (19.36 ± 7.01 versus 24.77 ± 4.68 versus 42.61 ± 7.49; p < 0.001); significant improvements in NITBUT, TFLL, CS, MGQ, MGEx, and OSDI were found in the IPL + DQS therapy and IPL therapy, while the sham therapy had no significant improvements. CONCLUSION: Combining 3% diquafosol ophthalmic solution with intense pulsed light was superior to IPL therapy alone in relieving the signs and symptoms of patients with severe evaporative DED. TRIAL REGISTRATION: Clinical Trials Identifier: NCT05694026.

Effects of Diquafosol Sodium Ophthalmic Solution on Tear Film Matrix Metallopeptidase-9 and Corneal Nerve Density in Patients with Type 2 Diabetic Dry Eye.

Purpose: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED's pathology. This preliminary short-term study aimed to evaluate the effects of 3% Diquafosol Sodium ophthalmic solution (DQS) on ocular surface inflammation and corneal nerve density in diabetic dry eye (DDE) patients. Methods: In this perspective, participants used 1 drop of 3% DQS (Diquas; Santen Pharmaceutical Co., Ltd., Osaka, Japan) 6 times daily for 8 weeks. Non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctival hyperemia [redness score (RS)], corneoconjunctival staining (CFS), corneal sensitivity (CS), Meibomian gland quality (MGQ) and Meibomian gland expressibility (MGEx), corneal nerve fiber density (CNFD), and Standard Patient Evaluation Eye Dryness (SPEED) questionnaire were assessed at baseline, at weeks 4, and up to 8 weeks. Matrix metalloproteinase-9 (MMP-9) of tear samples was measured at baseline and weeks 8. Results: The mean age was 61.27 ± 11.68 years. At baseline NITBUT = 5.89 ± 2.81 s, tear meniscus height = 0.17 ± 0.05 mm, TFLL = 2.74 ± 0.51, CFS = 4.35 ± 0.68, CS = 53.83 ± 9.63 mm, MMP-9 = 49.10 ± 10.42 ng/mL, RS = 1.65 ± 0.44, MGEx = 1.85 ± 0.72, MGQ = 2.65 ± 0.50, CNFD = 20.36 ± 8.20 no./mm2, and SPEED = 12.62 ± 3.91. At week 4, significant improvements were found in all parameters except RS (1.59 ± 0.46, P = 0.172) and CNFD (21.46 ± 8.41, P = 0.163). Finally, at week 8, all parameters had significant improvements. Conclusion: Preliminary short-term findings suggest that treatment of DDE patients with DQS was found to be safe and efficacious in improving dry eye parameters. In addition, inflammatory marker and corneal nerve density were significantly improved. This study was registered with ClinicalTrials.gov (NCT05193331).