Deepm6A-MT: A deep learning-based method for identifying RNA N6-methyladenosine sites in multiple tissues.

N6-methyladenosine (m6A) is the most prevalent, abundant, and conserved internal modification in the eukaryotic messenger RNA (mRNAs) and plays a crucial role in the cellular process. Although more than ten methods were developed for m6A detection over the past decades, there were rooms left to improve the predictive accuracy and the efficiency. In this paper, we proposed an improved method for predicting m6A modification sites, which was based on bi-directional gated recurrent unit (Bi-GRU) and convolutional neural networks (CNN), called Deepm6A-MT. The Deepm6A-MT has two input channels. One is to use an embedding layer followed by the Bi-GRU and then by the CNN, and another is to use one-hot encoding, dinucleotide one-hot encoding, and nucleotide chemical property codes. We trained and evaluated the Deepm6A-MT both by the 5-fold cross-validation and the independent test. The empirical tests showed that the Deepm6A-MT achieved the state of the art performance. In addition, we also conducted the cross-species and the cross-tissues tests to further verify the Deepm6A-MT for effectiveness and efficiency. Finally, for the convenience of academic research, we deployed the Deepm6A-MT to the web server, which is accessed at the URL http://www.biolscience.cn/Deepm6A-MT/.

Using three-dimensional modelling of the anterior sclera to investigate the scleral profile in myopic eyes.

PURPOSE: This study used three-dimensional (3D) modelling to investigate scleral profiles in myopic eyes and compare them with emmetropic eyes. METHODS: In this prospective observational study, the eyes of 151 participants were analysed using the corneoscleral profile module (CSP) of the Pentacam HR. Non-rotationally symmetrical ellipsoids were fitted to the anterior scleral sagittal height. Three radii were analysed, namely the nasal-temporal (Rx), superior-inferior (Ry) and anterior-posterior (Rz) orientations. Additionally, the area index (AI) and aspherical parameters (Qxy, Qxz and Qyz) of the anterior sclera-fitted ellipsoid (ASFE) were quantified. RESULTS: The findings showed an increase in Rx (-0.349 mm/D), Ry (-0.373 mm/D), Rz (-1.232 mm/D) and AI (-36.165 mm2 /D) with increasing myopia. From emmetropia to high myopia, the vertical and horizontal planes of the anterior sclera became increasingly prolate (emmetropia, Qxz: 0.02, Qyz: 0.01; low myopia, Qxz: -0.28, Qyz: -0.28; high myopia, Qxz: -0.41, Qyz: -0.43). There were no significant differences in the coronal plane across the three groups (H = 2.65, p = 0.27). The anterior scleral shape of high myopes in the horizontal and vertical planes was more prolate than that of emmetropes and low myopes (Qxz, high myopes vs. low myopes: p = 0.03, high myopes vs. emmetropes: p < 0.001; Qyz, high myopes vs. low myopes: p = 0.04, high myopes vs. emmetropes: p < 0.001). CONCLUSIONS: As the degree of myopia increased, non-uniform anterior scleral enlargement was observed. These findings provide a better understanding of the anterior segment with varying degrees of myopia.

Repeatability and Reproducibility of Corneoscleral Topography Measured With Scheimpflug Imaging in Keratoconus and Control Eyes.

OBJECTIVES: To determine and compare the repeatability and reproducibility of anterior scleral parameters measured by the corneoscleral profile (CSP) module of Pentacam in keratoconus (KC) and control eyes. METHODS: This is a prospective observational study. Thirty KC participants (30 eyes) and 24 control participants (24 eyes) were examined three times using the CSP. Sagittal height mean (SHM), sagittal height astigmatism (SHA), and mean bulbar slope (BSM) were measured in 12 mm and 16 mm chord lengths. The repeatability and reproducibility of these measurements were also assessed. Coefficients of variation (CoV), intraclass correlation coefficient (ICC), coefficient of repeatability (CoR1), and coefficient of reproducibility (CoR2) were adopted to assess the reliability. RESULTS: In the KC and control groups, SHM showed high repeatability and reproducibility (coefficients of variation [CoVs]≤0.96%, intraclass correlation coefficient [ICCs]≥0.97), and SHM of control eyes showed higher repeatability and reproducibility than that of KC eyes at 12 mm chord length (KC group, CoRs ranged from 35.56 µm to 43.52 µm, control group, ranged from 23.50 µm to 30.31 µm) and 16 mm chord length (KC group, CoRs ranged from 79.54 µm to 81.58 µm, control group, ranged from 48.25 µm to 66.10 µm). Mean bulbar slope also showed high repeatability and reproducibility (CoVs≤3.65%, CoRs≤2.64). Furthermore, the SHA of control eyes showed higher repeatability and reproducibility when compared with KC eyes (control group: CoVs≤29.95%, KC group: CoVs≥32.67%). CONCLUSIONS: Keratoconus and control eyes demonstrated high repeatability and reproducibility when using CSP measurements, which may prove helpful in fitting contact lenses.

Association between the posterior ocular contour pattern and progression of myopia in children: A prospective study based on OCT imaging.

PURPOSE: This study aims to reveal the relationship between the posterior ocular contour and the subsequent progression of myopia in children. METHODS: Children aged 8-12 years with myopia received baseline measurements and were instructed to wear their glasses every day and return for a follow-up visit after one year. Axial length and other ocular parameters were measured using a noncontact biometer. The contour of the posterior eye was calculated and analysed based on images from spectral domain optical coherence tomography (SD-OCT). Univariate and multivariate linear regression models were created to analyse the relationship between the contour of the posterior eye and the progression of myopia. RESULTS: Baseline posterior ocular contour measurements correlated with baseline axial length and spherical equivalent refraction (SER) (all p < 0.05). Eyes that were more myopic tended to have a more prolate posterior ocular contour. Although the baseline contour of the retinal pigment epithelium (RPE) and chorioscleral interface (CSI) showed no significant relationship with the progression of myopia (all p > 0.05), interestingly, when the baseline contour of the RPE was more prolate than that of the CSI, the axial length increased during the following year (R2  = 0.62; p < 0.01). The multivariate model, when adjusted for other variables, further validated the independent role of this variable. CONCLUSIONS: The difference between the RPE and CSI contours correlated with the subsequent progression of myopia in children. This finding can help inform clinicians regarding the management of children at the onset of myopia and potentially provide an avenue for experimental research on the mechanism of myopia development.

SoftVoting6mA: An improved ensemble-based method for predicting DNA N6-methyladenine sites in cross-species genomes.

The DNA N6-methyladenine (6mA) is an epigenetic modification, which plays a pivotal role in biological processes encompassing gene expression, DNA replication, repair, and recombination. Therefore, the precise identification of 6mA sites is fundamental for better understanding its function, but challenging. We proposed an improved ensemble-based method for predicting DNA N6-methyladenine sites in cross-species genomes called SoftVoting6mA. The SoftVoting6mA selected four (electron-ion-interaction pseudo potential, One-hot encoding, Kmer, and pseudo dinucleotide composition) codes from 15 types of encoding to represent DNA sequences by comparing their performances. Similarly, the SoftVoting6mA combined four learning algorithms using the soft voting strategy. The 5-fold cross-validation and the independent tests showed that SoftVoting6mA reached the state-of-the-art performance. To enhance accessibility, a user-friendly web server is provided at http://www.biolscience.cn/SoftVoting6mA/.

Axial Length Shortening after Combined Repeated Low-Level Red-Light Therapy in Poor Responders of Orthokeratology in Myopic Children.

Purpose: To investigate the efficacy and safety of orthokeratology (ortho-k) and repeated low-level red-light (RLRL) therapy in treating poor responders of ortho-k in myopic children. Methods: Study participants were 100 myopic children who completed two years of ortho-k treatment in a retrospective study. In the first year of ortho-k treatment (phase one), they experienced axial elongation of 0.30 mm or greater (defined as poor responders to ortho-k). Children were divided into two groups: the orthokeratology group (OK, n = 45) continued to receive ortho-k monotherapy and the combination group (OK-RLRL, n = 55) received RLRL in addition to ortho-k for the next year (phase two). Axial elongation over time between the groups was compared. Results: The mean age, male-to-female ratio, axial length (AL), and axial elongation in phase one were comparable between OK and OK-RLRL groups (all P > 0.05). During phase two, significant AL shortening was observed in the OK-RLRL group compared with children in the OK group (-0.10 ± 0.16 mm vs 0.30 ± 0.19 mm, P < 0.001). Among these 55 myopic children in the OK-RLRL group, 35 (63.6%), 25 (45.4%), 11 (20%), 6 (10.9%), and 3 (5.4%) of them had AL shortening over 0.05 mm/year, 0.10 mm/year, and 0.20 mm/year, 0.3 mm/year, and 0.4 mm/year, respectively. Older baseline age (ß = -0.02), higher treatment compliance (ß = -0.462), and AL change at 1 month (ß = 1.263) were significantly associated with less AL elongation (all P < 0.05). Conclusions: For poor responders of orthokeratology, RLRL could slow axial elongation in addition to the ortho-k treatment effect. Those who respond poorly to ortho-k with elder age might benefit more from combined therapy.

Association between vision-related quality of life and mental health status in myopia children using various optical correction aids.

PURPOSE: To evaluate the relationship between vision-related quality of life and mental health in myopia children with various optical aids. METHODS: This cross-sectional study enrolled children aged 8-13 years, exhibiting myopia ranging from -4.50 to -0.75 D, and utilizing various optical aids for correction. Full ocular examinations and completion of two questionnaires were performed. Vision-related quality of life was evaluated using the Paediatric Refractive Error Profile (PREP), and mental health status was assessed utilising the Screen for Child Anxiety Related Emotional Disorders (SCARED). Univariate and multivariate analyses were conducted to evaluate the association between vision-related quality of life and mental health status. RESULTS: The study sample comprised 209 children with corrected myopia using single vision spectacles (100 [47.8 %]), soft contact lenses (66 [31.6 %]), and orthokeratology lenses (43 [20.6 %]). The mean age was 10.31 ± 1.65 y, and males accounted for 50.7 % of the sample. The distribution of demographic characteristics showed no significant difference among all correction types, except that the myopia duration was longer for orthokeratology lens wearers than those using spectacles (P=0.03). Contact lens showed clear benefits in almost all dimensions of vision-related quality of life, especially in appearance, satisfaction, activity and peer perceptions dimensions. The prevalence of anxiety disorders among spectacle wearers was 25.0 %, the highest among all groups. For myopia children with optical corrections, not being in the top 30 percent of their class rank, reporting lower PREP scores on symptoms, handling and peer perceptions dimensions were related with a higher prevalence of anxiety disorders. CONCLUSIONS: Lower vision-related quality of life was associated with worse mental health status of myopia children with optical corrections. Identifying this association is crucial for protecting the mental health of myopia children and enhancing corrective measures.

HLH-30/TFEB modulates autophagy to improve proteostasis in Aß transgenic Caenorhabditis elegans.

Alzheimer's disease (AD) is a complex neurodegenerative disease that affects elderly individuals, characterized by senile plaques formed by extracellular amyloid beta (Aß). Autophagy dysfunction is a manifestation of protein homeostasis imbalance in patients with AD, but its relationship with Aß remains unclear. Here, we showed that in Aß transgenic Caenorhabditis elegans, Aß activated the TOR pathway and reduced the nuclear entry of HLH-30, leading to autophagy dysfunction characterized by autophagosome accumulation. Then, utilizing RNA-seq, we investigated the regulatory mechanisms by which HLH-30 modulates autophagy in C. elegans. We found that HLH-30 elevated the transcript levels of v-ATPase and cathepsin, thus enhancing lysosomal activity. This led to an increase in autophagic flux, facilitating more pronounced degradation of Aß. Moreover, HLH-30 reduced the level of ROS induction by Aß and enhanced the antioxidant stress capacity of the worms through the gsto-1 gene. Additionally, we identified two HLH-30/TFEB activators, saikosaponin B2 and hypericin, that improved autophagic flux, thereby enhancing protein homeostasis in C. elegans. Overall, our findings suggested that HLH-30/TFEB plays a key role in modulating autophagy and can be considered a promising drug target for AD treatments.

Long-term effect of orthokeratology on choroidal thickness and choroidal contour in myopic children.

PURPOSE: To investigate the long-term effect of orthokeratology (ortho-k) on the choroidal thickness and choroidal contour in myopic children. METHODS: Subjects were from a conducted 2-year randomised clinical trial. Children (n=80) aged 8-12 years with spherical equivalent refraction of -1.00 to -6.00D were randomly assigned to the control group (n=40) and ortho-k group (n=40). Optical coherence tomography images were collected at the baseline, 1-month, 6-month, 12-month, 18-month and 24-month visits, then the choroidal thickness and choroid contour were calculated. Axial length (AL) and other ocular biometrics were also measured. RESULTS: During 2 years, in the control group, the choroidal thickness became thinning and the choroidal contour became prolate with time at all visits (all p<0.001). Ortho-k can improve the choroidal thickness (all p<0.001) and maintain the choroidal contour at all visits (all p<0.05). In the ortho-k group, the choroidal contour was less changed in the temporal than nasal (p=0.008), and the choroidal thickness was more thickening in the temporal 3 mm (p<0.001). Two-year change in choroidal thickness was significantly associated with the 2-year AL change in the control group (r=-0.52, p<0.001), however, this trend was broken by ortho-k (r=-0.05, p=0.342). After being adjusted by other variables in the multivariable regression model, the effect of ortho-k on choroidal thickness was stable. CONCLUSIONS: In the current 2-year prospective study, ortho-k can improve the choroidal thickness and maintain the choroidal contour, but this effect diminished in a long term. Further study with larger sample size and longer follow-up is warranted to refine this issue.

Vision Improvement in Keratoconus Patients Trained With Perceptual Learning: A Randomized Controlled Trial.

PURPOSE: To investigate the effectiveness and maintenance of perceptional learning (PL) on vision improvement in keratoconus (KC) patients corrected with spectacles. DESIGN: Randomized, double-blind clinical trial. METHODS: Non-progressive KC patients 9 years of age or older who had best spectacle-corrected distance visual acuity (CDVA) of 0 to 1.0 logMAR (Snellen equivalent range 20/20 to 20/200) and who were contact lenses intolerant were enrolled. Eligible subjects were randomized into PL and control groups to receive PL and placebo training for 3 months, respectively. Spectacle-corrected visual acuity, contrast sensitivity function (CSF), stereoacuity, and visual functioning and quality of life were measured at baseline, 3 months, and 6 months of follow-up. Statistics were analyzed following the intention-to-treat principle. RESULTS: After 3 months of training, the CDVA of patients in the PL group improved as compared to the placebo group (0.17 ± 0.15 logMAR vs 0.02 ± 0.06 logMAR; P = .0006). Eight of 17 (47.06%) patients in the PL group reached CDVA improvement ≥2 lines (P = .0010). This improvement persisted for at least 6 months (from baseline) as compared to the placebo group (0.17 ± 0.17 logMAR vs 0.01 ± 0.07 logMAR; P = .0011). The increase in CSF in the PL group mainly was found for moderate spatial frequency (0.11 ± 0.17 log units at 3 cpd; 0.12 ± 0.19 log units at 6 cpd). Linear regression indicated that patients with worse initial CDVA achieved better gains in CDVA after PL (P = .009). No side effects were observed, and no subjects withdrew from the study because of training difficulties. CONCLUSIONS: Three-month PL improved vision in KC patients, and the improvement was maintained after 3 months of treatment cessation. The results indicate that PL may be a promising therapy for KC patients with unsatisfied spectacle-corrected visual acuity.

BiDFDC-Net: a dense connection network based on bi-directional feedback for skin image segmentation.

Accurate segmentation of skin lesions in dermoscopic images plays an important role in improving the survival rate of patients. However, due to the blurred boundaries of pigment regions, the diversity of lesion features, and the mutations and metastases of diseased cells, the effectiveness and robustness of skin image segmentation algorithms are still a challenging subject. For this reason, we proposed a bi-directional feedback dense connection network framework (called BiDFDC-Net), which can perform skin lesions accurately. Firstly, under the framework of U-Net, we integrated the edge modules into each layer of the encoder which can solve the problem of gradient vanishing and network information loss caused by network deepening. Then, each layer of our model takes input from the previous layer and passes its feature map to the densely connected network of subsequent layers to achieve information interaction and enhance feature propagation and reuse. Finally, in the decoder stage, a two-branch module was used to feed the dense feedback branch and the ordinary feedback branch back to the same layer of coding, to realize the fusion of multi-scale features and multi-level context information. By testing on the two datasets of ISIC-2018 and PH2, the accuracy on the two datasets was given by 93.51% and 94.58%, respectively.

Improved U-Net based on cross-layer connection for pituitary adenoma MRI image segmentation.

Pituitary adenoma is a common neuroendocrine neoplasm, and most of its MR images are characterized by blurred edges, high noise and similar to surrounding normal tissues. Therefore, it is extremely difficult to accurately locate and outline the lesion of pituitary adenoma. To sovle these limitations, we design a novel deep learning framework for pituitary adenoma MRI image segmentation. Under the framework of U-Net, a newly cross-layer connection is introduced to capture richer multi-scale features and contextual information. At the same time, full-scale skip structure can reasonably utilize the above information obtained by different layers. In addition, an improved inception-dense block is designed to replace the classical convolution layer, which can enlarge the effectiveness of the receiving field and increase the depth of our network. Finally, a novel loss function based on binary cross-entropy and Jaccard losses is utilized to eliminate the problem of small samples and unbalanced data. The sample data were collected from 30 patients in Quzhou People's Hospital, with a total of 500 lesion images. Experimental results show that although the amount of patient sample is small, the proposed method has better performance in pituitary adenoma image compared with existing algorithms, and its Dice, Intersection over Union (IoU), Matthews correlation coefficient (Mcc) and precision reach 88.87, 80.67, 88.91 and 97.63%, respectively.

Modified UNet++ with atrous spatial pyramid pooling for blood cell image segmentation.

Blood cell image segmentation is an important part of the field of computer-aided diagnosis. However, due to the low contrast, large differences in cell morphology and the scarcity of labeled images, the segmentation performance of cells cannot meet the requirements of an actual diagnosis. To address the above limitations, we present a deep learning-based approach to study cell segmentation on pathological images. Specifically, the algorithm selects UNet++ as the backbone network to extract multi-scale features. Then, the skip connection is redesigned to improve the degradation problem and reduce the computational complexity. In addition, the atrous spatial pyramid pooling (ASSP) is introduced to obtain cell image information features from each layer through different receptive domains. Finally, the multi-sided output fusion (MSOF) strategy is utilized to fuse the features of different semantic levels, so as to improve the accuracy of target segmentation. Experimental results on blood cell images for segmentation and classification (BCISC) dataset show that the proposed method has significant improvement in Matthew's correlation coefficient (Mcc), Dice and Jaccard values, which are better than the classical semantic segmentation network.

Group theoretic particle swarm optimization for gray-level medical image enhancement.

As a principal category in the promising field of medical image processing, medical image enhancement has a powerful influence on the intermedia features and final results of the computer aided diagnosis (CAD) system by increasing the capacity to transfer the image information in the optimal form. The enhanced region of interest (ROI) would contribute to the early diagnosis and the survival rate of patients. Meanwhile, the enhancement schema can be treated as the optimization approach of image grayscale values, and metaheuristics are adopted popularly as the mainstream technologies for medical image enhancement. In this study, we propose an innovative metaheuristic algorithm named group theoretic particle swarm optimization (GT-PSO) to tackle the optimization problem of image enhancement. Based on the mathematical foundation of symmetric group theory, GT-PSO comprises particle encoding, solution landscape, neighborhood movement and swarm topology. The corresponding search paradigm takes place simultaneously under the guidance of hierarchical operations and random components, and it could optimize the hybrid fitness function of multiple measurements of medical images and improve the contrast of intensity distribution. The numerical results generated from the comparative experiments show that the proposed GT-PSO has outperformed most other methods on the real-world dataset. The implication also indicates that it would balance both global and local intensity transformations during the enhancement process.

Changes in Stress-Strain Index in School-Aged Children: A 3-Year Longitudinal Study.

Purpose: To determine three-year change of the corneal biomechanical parameter stress-strain index (SSI) in schoolchildren aged 7- 9 years and their correlation with refractive error and axial length (AL). Methods: This is a prospective cohort study. Data of the AL, refractive error, and corneal biomechanical parameter SSI were collected at baseline and a 3-year follow-up for 217 schoolchildren. SSI, AL, and refractive error were measured via corneal visualization Scheimpflug technology (Corvis ST), IOLMaster biometry, and cycloplegic refraction. Three years of changes in SSI and its association with refractive error and AL were analyzed. Participants were divided into persistent nonmyopia (PNM), newly developed myopia (NDM), and persistent myopia (PM). The three-year difference in SSI among the three groups was analyzed. Results: After three years of follow-up, the corneal biomechanical parameter SSI decreased in all participants (P < 0.01). There was a negative correlation between the change in SSI and the change in AL (r = -0.205, P=0.002) and a positive correlation between the change in refractive error (r = 0.183, P=0.007). After three years of follow-up, there was a decrease in the SSI for the NDM, PM, and PNM participants, with a median change of -0.05 for PNM and -0.13 and -0.09 for the NDM and PM, respectively. There was a significant decrease in corneal biomechanical properties for NDM patients compared with PNM patients (P < 0.01). Conclusion: In 7- to 9-year-old schoolchildren, SSI decreased after three years of the longitudinal study, and the change in SSI was correlated with the change in AL and refractive error. There was a rapid decrease in corneal biomechanical properties among newly developed myopic patients.

Effect of COVID-19 home confinement on the efficacy of orthokeratology, 0.01% atropine and combined treatment.

PURPOSE: To investigate the effect of COVID-19 home confinement on the efficacy of the interventions for controlling myopia, and to select effective therapies to control myopia during COVID-19 confinement. METHOD: Children (n = 164) aged 8-12 years with spherical equivalent refraction of -1.00 to -6.00 diopters were stratified into two age subgroups and randomly allocated into the control, 0.01% atropine, orthokeratology (ortho-k) and atropine combined ortho-k (ACO) groups. Axial length (AL) was measured at baseline, 6-, 12-, 18- and 24-month visits. The follow-up spanned the period before the COVID-19 outbreak, the period of the home confinement, and the period of the school reopening. Hence, the AL change in different periods was collected and compared. Data analysis was performed following the criteria of intention to treat (ITT). RESULTS: All 164 children were involved in the ITT analysis. Compared to control, all interventions can still reduce the AL elongation during the COVID-19 home confinement period (all p < 0.05). However, the efficacy was compromised: individuals experienced more AL elongation during the COVID-19 home confinement period in the control, 0.01% atropine and ACO groups (all p < 0.05). Interestingly, in the ortho-k group, the difference was insignificant (p = 0.178), and the interaction between the intervention type (control vs. ortho-k) and the confinement severity was significant (p for interaction = 0.041), which is different from the atropine (p for interaction = 0.248) or ACO group (p for interaction = 0.988). These results were stable after being adjusted by other variables based on the multivariable regression model. CONCLUSION: Ortho-k was less affected by the COVID-19 home confinement, which is potentially a better therapy for children in this high-risk environment. Further investigations are warranted to validate this issue.

Accommodation and vergence function in children using atropine combined with orthokeratology.

PURPOSE: This study aimed to evaluate binocular vision in terms of vergence and accommodative measurements in children treated with 0.01% atropine combined with orthokeratology (OK). METHODS: This was a prospective and randomized controlled clinical trial involving participants aged 8 to 12 years, with a spherical equivalent (SE) ranging from - 1.00 to - 6.00D. Participants were randomly divided into four groups: 1) a combination group using 0.01% atropine solution and OK lens; 2) an OK group using placebo solution and OK lens; 3) an atropine group using 0.01% atropine solution and wearing spectacles; and 4) a control group using placebo solution and wearing spectacles. Binocular vision was determined at baseline and at 3-month visits, with evaluations including horizontal phoria, fusional vergence, the accommodative convergence/accommodation (AC/A) ratio, accommodative lag, and accommodative amplitude (AA). The Wilcoxon signed-rank test was used to compare the changes in binocular vision in each group, and the Kruskal-Wallis test was used for comparisons of four groups. RESULTS: Sixty-two participants completed the study. There was no significant difference in baseline refraction, accommodation or vergence measurements among the groups (all P > 0.05). Three months later, the accommodative lag significantly decreased in the OK group (P = 0.002) but remained unchanged in the other three groups (all P > 0.05). In addition, binocular accommodative facilities and positive relative accommodations increased in the combination and OK groups (both P < 0.05) but remained unchanged in the atropine and control groups (both P > 0.05). Only the participants with esophoria in the OK group had a significant decrease in esophoria (P = 0.008). Moreover, the changes in fusional vergence and AC/A did not significantly differ between the four groups (all P > 0.05). CONCLUSION: Accommodative measurements changed similarly in the groups treated with OK. Changes in vergence measurements after treatment with 0.01% atropine were not significant.

Effect of atropine, orthokeratology and combined treatments for myopia control: a 2-year stratified randomised clinical trial.

PURPOSE: To investigate the 2-year efficacy of atropine, orthokeratology (ortho-k) and combined treatment on myopia. To explore the factors influencing the efficacy. METHODS: An age-stratified randomised controlled trial. Children (n=164) aged 8-12 years with spherical equivalent refraction of -1.00 to -6.00 D were stratified into two age subgroups and randomly assigned to receive placebo drops+spectacles (control), 0.01% atropine+spectacles (atropine), ortho-k+placebo (ortho-k) or combined treatment. Axial length was measured at baseline and visits at 6, 12, 18 and 24 months. The primary analysis was done following the criteria of intention to treat, which included all randomised subjects. RESULTS: All interventions can significantly reduce axial elongation at all visits (all p<0.05). Overall, the 2-year axial elongation was significantly reduced in combined treatment than in monotherapies (all p<0.05). After stratification by age, in the subgroup aged 8-10, the difference between combined treatment and ortho-k became insignificant (p=0.106), while in the subgroup aged 10-12, the difference between combined treatment and atropine became insignificant (p=0.121). A significant age-dependent effect existed in the ortho-k group versus the control group (p for interaction=0.013), and a significant age-dependent effect existed in the ortho-k group versus the atropine group (p for interaction=0.035), which indicated that ortho-k can achieve better efficacy in younger children. CONCLUSIONS: Atropine combined with ortho-k treatment can improve the efficacy of myopia control compared with monotherapy in children aged 8-12. Younger children might benefit more from ortho-k. TRIAL REGISTRATION NUMBER: ChiCTR1800015541.

Liensinine and neferine exert neuroprotective effects via the autophagy pathway in transgenic Caenorhabditis elegans.

BACKGROUND: Liensinine and neferine are the main bisbenzylisoquinoline alkaloids obtained from the seeds of Nelumbo nucifera, which commonly used as edible food and traditional medicine in Asia. It was reported that liensinine and neferine could inhibit the activities of acetylcholinesterase and cross the blood-brain barriers, suggesting their therapeutic potential for the management of Alzheimer's disease. METHODS: Here, we employed SH-SY5Y human neuroblastoma cells stably transfected with the human Swedish amyloid precursor protein (APP) mutation APP695 (APP695swe SH-SY5Y) as an in vitro model and transgenic Caenorhabditis elegans as an in vivo model to investigate the neuroprotective effects and underlying mechanism of liensinine and neferine. RESULTS: We found that liensinine and neferine could significantly improve the viability and reduce ROS levels in APP695swe SH-SY5Y cells, inhibit ß-amyloid and tau-induced toxicity, and enhance stress resistance in nematodes. Moreover, liensinine and neferine had obviously neuroprotective effects by assaying chemotaxis, 5-hydroxytryptamine sensitivity and the integrity of injured neurons in nematodes. Preliminary mechanism studies revealed that liensinine and neferine could upregulate the expression of autophagy related genes (lgg-1, unc-51, pha-4, atg-9 and ced-9) and reduce the accumulation of ß-amyloid induced autophagosomes, which suggested autophagy pathway played a key role in neuroprotective effects of these two alkaloids. CONCLUSIONS: Altogether, our findings provided a certain working foundation for the use of liensinine and neferine to treat Alzheimer's disease based on neuroprotective effects.

Long-Term Axial Length Shortening in Myopic Orthokeratology: Incident Probability, Time Course, and Influencing Factors.

Purpose: Long-term axial length (AL) shortening in myopia is uncommon but noteworthy. Current understanding on the condition is limited due to difficulties in case collection. The study reported percentage, probability, and time course of long-term AL shortening in myopic orthokeratology based on a large database. Methods: This study reviewed 142,091 medical records from 29,825 subjects in a single-hospital orthokeratology database that were collected over 10 years. Long-term AL shortening was defined as a change in AL of -0.1 mm or less at any follow-up beyond 1 year. Incident probability was calculated based on multivariate logistic regression. Time course was estimated using mixed-effect regression model. Results: A total of 10,093 subjects (mean initial age, 11.70 ± 2.52 years; 58.8% female) with 80,778 visits were included. The number of subjects experienced long-term AL shortening was 1,662 (16.47%; 95% confidence interval, 15.75%-17.21%). Initial age showed significant impact on the incident occurrence (OR, 1.37; 95% confidence interval, 1.34-1.40; P < 0.001). The estimated probability of AL shortening was approximately 2% for subjects with initial age of 6 years and 50% for those aged 18. Among the 1662 AL shortening cases, the median magnitude of the maximum AL reduction was 0.19 mm. The shortening process mostly occurred within the initial 2 years. Subject characteristics had limited associations with the shortening rate. Conclusions: Long-term AL shortening is possible in subjects receiving myopic orthokeratology. Although age notably affect the incident probability, the time course seems to not vary significantly.