Effect of low-dose atropine eyedrops on pupil metrics: results after half a year of treatment and cessation.

PURPOSE: To evaluate the effect of low-dose atropine eyedrops on pupil metrics. METHODS: This study was based on a randomized, double-masked, placebo-controlled, and cross-over trial in mainland China. In phase 1, subjects received 0.01% atropine or placebo once nightly. After 1 year, the atropine group switched to placebo (atropine-placebo group), and the placebo group switched to atropine (placebo-atropine group). Ocular parameters were measured at the crossover time point (at the 12th month) and the 18th month. RESULTS: Of 105 subjects who completed the study, 48 and 57 children were allocated into the atropine-placebo and placebo-atropine groups, respectively. After cessation, the photopic pupil diameter (PD) and mesopic PD both decreased (- 0.46 ± 0.47 mm, P < 0.001; - 0.30 ± 0.74 mm, P = 0.008), and the constriction ratio (CR, %) increased (4.39 ± 7.54, P < 0.001) compared with values at the crossover time point of the atropine-placebo group; pupil metrics of the atropine-placebo group had no difference from the values at the crossover time point of the placebo-atropine group. After 6 months of treatment, the photopic PD and the mesopic PD increased (0.54 ± 0.67 mm, P < 0.001; 0.53 ± 0.89 mm, P < 0.001), the CR (%) decreased (- 2.53 ± 8.64, P < 0.001) compared with values at the crossover time point of the placebo-atropine group. There was no significant relationship between pupil metrics and myopia progression during 0.01% atropine treatment. CONCLUSION: Pupil metrics and the CR could return to pre-atropine levels after cessation. Pupil metrics had no significant effect on myopia progression during treatment.

Effect of Atropine 0.01% Eye Drops on the Difference in Refraction and Axial Length between Right and Left Eyes.

INTRODUCTION: This study sought to determine whether the application of 0.01% atropine eye drops could impact the disparity in refraction and axial length (AL) between the right and left eyes in Chinese children. METHODS: The study was designed as a double-blind, placebo-controlled randomized trial. A total of 220 children aged 6-12 years were recruited from the Beijing Tongren Hospital in Beijing, China. Participants were randomized in a 1:1 ratio and were prescribed 0.01% atropine or placebo eye drops to be administered once a night to both eyes for the duration of 1 year. The cycloplegic refraction and AL were recorded including baseline, 6 months, and again at the 12 months. RESULTS: After 1-year follow-up period, 76 (69%) and 83 (75%) subjects of the initial 220 participants were identified as the 0.01% atropine and placebo groups, respectively. The inter-ocular difference in spherical equivalent refraction (SER) and AL demonstrated stable values in the 0.01% atropine treatment group (SER: p = 0.590; AL: p = 0.322) analyzed after 1 year, but found a significant increase (SER: p < 0.001; AL: p = 0.001) in the placebo group. Furthermore, over 1 year, eyes with greater myopia in the atropine group exhibited slower myopia progression (0.45 ± 0.44 D) than the lesser myopic eye (0.56 ± 0.44 D) (p = 0.003). CONCLUSION: This study demonstrated that 0.01% atropine could maintain the inter-ocular SER and AL difference. And 0.01% atropine appeared to be more effective in delaying the progression of myopia in eyes with more myopia than in the less myopic eyes.

[Study on HPLC fingerprint and chemical constituent difference of different species of Aurantii Fructus Immaturus].

This study is to establish an HPLC fingerprint by HPLC-DAD method and simultaneous quantitative analysis of 17 components of 18 batches of Citrus aurantium and 10 batches of C. sinensis. The separation was performed on an Agilent Poroshell 120 SB-C18 (4.6 mm×100 mm,2.7 µm) column with the gradient elution of methanol-0.1% formic acid water, the flow was 0.6 mL•min⁻¹. The detection wavelength was set at 318 nm. The column temperature was maintained at 30 ℃. The data calculation was performed with similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (Version 2004A) together with SIMCA-P 13.0 software to clarify the differential marker between these two different species of Aurantii Fructus Immaturus. This method has good precision stability and repeatability that could provide basis for quality control and evaluation of Aurantii Fructus Immaturus.

Repeatability and agreement between a reference Scheimpflug tomographer and a low-cost Scheimpflug system.

PURPOSE: To assess the repeatability and agreement between Scheimpflug-based corneal topographers, Scansys and Pentacam, in measuring ocular parameters in myopic eyes. SETTING: Grade-A tertiary hospital in Beijing, China. DESIGN: Cross-sectional study. METHODS: The following measurements were performed in 204 subjects undergoing preoperative examinations for refractive surgery from the corneal curvature, astigmatism, corneal thickness, corneal volume, corneal asphericity, anterior chamber depth (ACD) and volume (ACV), and pupil diameters. Repeatability was determined using intraclass correlation coefficient with 95% CI, Cronbach α, coefficient of variation, within-subject SD, test-retest repeatability, and 1-way analysis of variance (1-way analysis of variance). The interdevice agreement was determined using paired t test and Bland-Altman plots. RESULTS: Scansys showed good repeatability in the anterior and posterior corneal flattest meridian (Kf), steepest meridian (Ks), and mean (Km); axis of anterior corneal Ks; anterior corneal astigmatism; pupil central corneal thickness (CCT); CCT; corneal apex thickness; thinnest corneal thickness; corneal volume; photopic pupil diameter; ACD; and ACV. In the agreement study, Bland-Altman plots showed that 95% limit of agreement of corneal curvature, pupil CCT, corneal apex thickness, thinnest corneal thickness, and corneal volume generated by Scansys and Pentacam were narrow. There were no statistically significant differences in the anterior corneal Kf and Km. CONCLUSIONS: Scansys showed good repeatability in measuring corneal curvature of anterior and posterior surfaces, anterior corneal astigmatism, corneal thickness, corneal volume, photopic pupil diameter, ACV, and ACD. Scansys and Pentacam can only be used interchangeably in measuring anterior corneal curvature.

Myopia progression after cessation of low-dose atropine eyedrops treatment: A two-year randomized, double-masked, placebo-controlled, cross-over trial.

PURPOSE: The purpose of the study was to evaluate myopia progression and axial elongation after stopping 0.01% atropine eye drops through a 2-year cross-over study. METHODS: This study was a randomized, double-masked, placebo-controlled, cross-over trial in mainland China. 220 children aged 6-12 years with spherical equivalent range of -1.00 D to -6.00 D in both eyes were enrolled in Phase 1 for 1 year. Children who had completed the first year's follow-up continued in the second phase. In Phase 2, the placebo group was crossed over to the 0.01% atropine group (referred to as the 'placebo-atropine group'), and the 0.01% atropine group was crossed over to the placebo group (referred to as the 'atropine-placebo group'). All children underwent the examination of cycloplegic refraction and axial length at a 6-month interval. Only data from right eyes were included in analysis. RESULTS: One hundred thirty-three subjects completed 2 years of follow-up. In the first year, the mean myopia progression in atropine-placebo group was 0.21 ± 0.08 D slower than that in placebo-atropine group. After cross-over treatment, the mean myopia progression in atropine-placebo group was 0.22 ± 0.07D faster than that in placebo-atropine group in the second year. Over 2 years, the mean myopia progression was -1.26 ± 0.66D and -1.25 ± 0.70D in the atropine-placebo and placebo-atropine groups (p = 0.954). CONCLUSIONS: The difference in myopia progression between atropine-placebo group and placebo-atropine group in Phase 1 was similar to Phase 2 during the cross-over treatment. Through our cross-over trial, the results suggest that there is no rebound effect after using 0.01% atropine eye drops to prevent progression of myopia.

Zonule-Associated Gene Variants in Isolated Ectopia Lentis and Glaucoma.

PRCIS: We report 3 novel variants in fibrillin-1 (FBN1) and latent transforming growth factor-ß-binding protein 2 (LTBP2) in 3 families with isolated ectopia lentis (EL), which shed new light on the diagnosis and genetic counseling of EL and secondary glaucoma in clinical settings. PURPOSE: To explore the genetic mechanism in 3 families with isolated EL and secondary angle closure glaucoma. METHODS: Three Han Chinese families with EL and glaucoma were recruited. All of the participants underwent complete ocular and general physical examinations and DNA samples were extracted from peripheral venous blood and screened for disease-causing variants using whole exome and Sanger sequencing. In silico analyses were performed to predict the structural and functional changes in gene variants and abnormal proteins. RESULTS: All 3 probands presented with EL and pupillary-blocking glaucoma. Genetic testing showed that all the patients have zonule-related gene mutations, with the proband (II:1), as well as his mother (I:2) and daughters (III:1 and III:2) from family 1 carrying a heterozygous mutation in FBN1 gene (c.6493G>T:p.(V2165L)); the proband (II:1) from family 2 carrying a heterozygous mutation in FBN1 gene (c.2543C>A:p.(T848N)), and the proband (II:1) from family 3 carrying a pair of compound heterozygous mutations in LTBP2 gene (c.4825T>A:p.(C1609S) / c.529T>C:p.(W177R)). No other genetic variants were found to be associated with the phenotypes of patients and other family members in this study. All variants are predicted to affect the structure and function of proteins as risk factors for EL based on bioinformatics analysis. CONCLUSION: Four novel mutations were identified in 3 families with EL, suggesting an intimate link between specific mutations in FBN1 and LTBP2 and isolated EL and angle closure glaucoma. Our results expanded the variant spectrum of zonule-related genes and helped explore the underlying molecular pathology of these disorders.

Effect of Age and Refractive Error on Local and Global Visual Perception in Chinese Children and Adolescents.

PURPOSE: This study investigated the impact of age and myopia on visual form perception among Chinese school-age children. METHODS: This cross-sectional study included 1,074 students with a mean age of 12.1 ± 4.7 (range = 7.3-18.9) years. The mean spherical equivalence refraction (SER) of the participants was -1.45 ± 2.07 D. All participants underwent distance visual acuity (VA), refraction measurement and local and global visual form perception test including orientation, parallelism, collinearity, holes and color discrimination tasks. RESULTS: The reaction times of emmetropes were slower than those of myopic and high myopic groups on both local (orientation, parallelism, and collinearity) and global discrimination tasks (all p < 0.05). A reduction in reaction times was found with increasing age on both local and global discrimination tasks (all p < 0.05). Age was significantly associated with both local and global visual perception performance after adjusting for gender, visual acuity and SER (orientation, ß = -0.54, p < 0.001; parallelism, ß = -0.365, p < 0.001; collinearity, ß = -0.28, p < 0.001; holes, ß = -0.319, p < 0.001; color, ß = -0.346, p < 0.001). CONCLUSIONS: This study revealed that both local and global visual perception improve with age among Chinese children and that myopes seem to have better visual perception than emmetropes.

Machine Learning to Determine Risk Factors for Myopia Progression in Primary School Children: The Anyang Childhood Eye Study.

INTRODUCTION: To investigate the risk factors for myopia progression in primary school children and build prediction models by applying machine learning to longitudinal, cycloplegic autorefraction data. METHODS: A total of 2740 children from grade 1 to grade 6 were examined annually over a period of 5 years. Myopia progression was determined as change in cycloplegic autorefraction. Questionnaires were administered to gauge environmental factors. Each year, risk factors were evaluated and prediction models were built in a training group and then tested in an independent hold-out group using the random forest algorithm. RESULTS: Six variables appeared in prediction models on myopia progression for all 5 years, with combined weight of 77% and prediction accuracy over 80%. Uncorrected distance visual acuity (UDVA) had the greatest weight (mean 28%, range 22-39%), followed by spherical equivalent (20%, 7-28%), axial length (13%, 10-14%), flat keratometry reading (K1) (7%, 4-11%), gender (6%, 2-9%), and parental myopia (3%, 1-10%). UDVA and spherical equivalent had peak weight at the second and third study years, respectively. The weight of myopic parents decreased steadily over the 5 years (9.5%, 1.9%, 1.8%, 1%, and 1.3%). Weekly time spent reading, reading distance, reading in bed, and frequency of eating meat were included as variables in different study years. CONCLUSIONS: Myopia progression in children was predicted well by machine learning models. UDVA and spherical equivalents were good predictive factors for myopia progression in children through primary school. Parental myopia was found to play a substantial role in the early stage of myopia progression but waned as children grew older.

Association Between Color Vision Deficiency and Myopia in Chinese Children Over a Five-Year Period.

Purpose: To explore the relationship of color vision deficiency with myopia progression and axial elongation in Chinese primary school children during a five-year cohort study. Methods: A total of 2849 grade 1 students (aged 7.1 ± 0.4 years) from 11 primary schools were enrolled and followed up for five years. Cycloplegic autorefraction and axial length were measured annually. Color vision testing was performed using Ishihara's test and the City University color vision test. Results: The prevalence of color vision deficiency was 1.68%, with 2.81% in boys and 0.16% in girls. Color-deficient cases consisted of 91.6% deutan and 8.3% protan. Over the five years, the cumulative incidence of myopia was 35.4% (17/48) in the color-vision deficiency group, which was lower than the 56.7% (1017/1794) in the color normal group (P = 0.004). Over the five-year study period, the change in spherical equivalent refraction in the color vision-deficiency group (-1.81 D) was also significantly lower than that in the color normal group (-2.41 D) (P = 0.002). Conclusions: The lower incidence and slower progression of myopia in children with color-vision deficiency over the five-year follow-up period suggest that color-deficient individuals are less susceptible to myopia onset and development.

Ocular Perfusion Pressure in 7- and 12-Year-Old Chinese Children: The Anyang Childhood Eye Study.

Purpose: The purpose of this study was to report the distribution of mean ocular perfusion pressure (MOPP) and its associated factors in Chinese children. Methods: We enrolled 3048 grade 1 students and 2258 grade 7 students of the Anyang Childhood Eye Study in central China. Systolic and diastolic blood pressure (SBP and DBP) were recorded with a digital automatic sphygmomanometer. Intraocular pressure (IOP) was assessed by a non-contact tonometer. MOPP was calculated as 2/3 × (DBP + 1/3[SBP - DBP]) - IOP. Risk factors for myopia were obtained through a questionnaire survey. Results: The MOPP was 33.83 ± 6.37 mm Hg (mean ± SD) in grade 1, which was lower than 36.99 ± 6.80 mm Hg in grade 7 (P < 0.001). Compared with myopic eyes, non-myopic eyes had higher MOPP in grade 7 (37.72 ± 6.72 mm Hg versus 36.58 ± 6.57 mm Hg, P < 0.001) and in grade 1 (33.88 ± 6.29 mm Hg versus 33.12 ± 7.03 mm Hg, P = 0.12). Multivariable analysis showed that higher MOPP was associated with less myopia (P < 0.001), higher body mass index (BMI; P < 0.001), thinner central corneal thickness (P < 0.001), less time on near work (P < 0.001), and more time on sleeping (P = 0.04). Conclusions: MOPP was higher in children of older age, with higher BMI, less time on near work, and more time on sleeping, and was higher in eyes with less myopia. Translational Relevance: We found that MOPP might be an indicator for the detection of myopia development.

Effect of 0.01% atropine eyedrops on intraocular pressure in schoolchildren: a randomized clinical trial.

AIM: To assess the effect of 0.01% atropine eye drops on intraocular pressure (IOP) in myopic children. METHODS: A placebo-controlled, double-masked, randomized study. Totally 220 children aged 6 to 12y with myopia ranging from -1.00 to -6.00 D in both eyes were enrolled. Children were randomized in a 1:1 ratio to either 0.01% atropine eye drops or a placebo group using generated random numbers. All participants underwent the examination of IOP and cycloplegic refraction at baseline, 6 and 12mo. The change of IOP and the proportion of subjects with increased IOP in atropine and placebo groups were compared. RESULTS: Of 220 children, 117 were boys (53.2%). A total of 159 (72.3%) participants completed the follow-up at the 1-year study. At baseline, the mean IOP was 15.74 mm Hg (95%CI, 15.13 to 16.34 mm Hg) for the 0.01% atropine group and 15.59 mm Hg (95%CI, 15.00 to 16.19 mm Hg) for placebo group (mean difference, 0.14 mm Hg; P=0.743) after adjusting for central corneal thickness at baseline. At one year follow-up, the mean change of IOP was 0.16 mm Hg (95%CI, -0.43 to 0.76 mm Hg) for the 0.01% atropine group and -0.11 mm Hg (95%CI, -0.71 to 0.50 mm Hg) for placebo group (mean difference, 0.27 mm Hg; P=0.525) after adjusting for central corneal thickness. The 51.4% of children have increased IOP in the 0.01% atropine group, compared with 45.9% in the placebo group (P=0.511). CONCLUSION: The 0.01% atropine eye drops do not significantly affect the risk of elevated IOP. It is relatively safer to use in the studies that try to minimize myopia progression. However, a further long-duration study is required to be validated.

Effect of Text Messaging Parents of School-Aged Children on Outdoor Time to Control Myopia: A Randomized Clinical Trial.

Importance: Myopia in school-aged children is a public health issue worldwide; consequently, effective interventions to prevent onset and progression are required. Objective: To investigate whether SMS text messages to parents increase light exposure and time outdoors in school-aged children and provide effective myopia control. Design, Setting, and Participants: This randomized clinical trial was conducted in China from May 2017 to May 2018, with participants observed for 3 years. Of 528 965 primary school-aged children from Anyang, 3113 were randomly selected. Of these, 268 grade 2 schoolchildren were selected and randomly assigned to SMS and control groups. Data were analyzed from June to December 2021. Interventions: Parents of children in the SMS group were sent text messages twice daily for 1 year to take their children outdoors. All children wore portable light meters to record light exposure on 3 randomly selected days (2 weekdays and 1 weekend day) before and after the intervention. Main Outcomes and Measures: The co-primary outcomes were change in axial length (axial elongation) and change in spherical equivalent refraction (myopic shift) from baseline as measured at the end of the intervention and 3 years later. A secondary outcome was myopia prevalence. Results: Of 268 grade 2 schoolchildren, 121 (45.1%) were girls, and the mean (SD) age was 8.4 (0.3) years. Compared with the control group, the SMS intervention group demonstrated greater light exposure and higher time outdoors during weekends, and the intervention had significant effect on axial elongation (coefficient, 0.09; 95% CI, 0.02-0.17; P = .01). Axial elongation was lower in the SMS group than in the control group during the intervention (0.27 mm [95% CI, 0.24-0.30] vs 0.31 mm [95% CI, 0.29-0.34]; P = .03) and at year 2 (0.39 mm [95% CI, 0.35-0.42] vs 0.46 mm [95% CI, 0.42-0.50]; P = .009) and year 3 (0.30 mm [95% CI, 0.27-0.33] vs 0.35 mm [95% CI, 0.33-0.37]; P = .005) after the intervention. Myopic shift was lower in the SMS group than in the control group at year 2 (-0.69 diopters [D] [95% CI, -0.78 to -0.60] vs -0.82 D [95% CI, -0.91 to -0.73]; P = .04) and year 3 (-0.47 D [95% CI, -0.54 to -0.39] vs -0.60 D [95% CI, -0.67 to -0.53]; P = .01) after the intervention, as was myopia prevalence (year 2: 38.3% [51 of 133] vs 51.1% [68 of 133]; year 3: 46.6% [62 of 133] vs 65.4% [87 of 133]). Conclusions and Relevance: In this randomized clinical trial, SMS text messages to parents resulted in lower axial elongation and myopia progression in schoolchildren over 3 years, possibly through increased outdoor time and light exposure, showing promise for reducing myopia prevalence. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOC-17010525.

Brain Activation Induced by Myopic and Hyperopic Defocus From Spectacles.

Purpose: To assess neural changes in perceptual effects induced by myopic defocus and hyperopic defocus stimuli in ametropic and emmetropic subjects using functional magnetic resonance imaging (fMRI). Methods: This study included 41 subjects with a mean age of 26.0 ± 2.9 years. The mean spherical equivalence refraction was -0.54 ± 0.51D in the emmetropic group and -3.57 ± 2.27D in the ametropic group. The subjects were instructed to view through full refractive correction, with values of +2.00D to induce myopic defocus state and -2.00D to induce hyperopic defocus state. This was carried over in three random sessions. Arterial spin labeling (ASL) perfusion was measured using fMRI to obtain quantified regional cerebral blood flow (rCBF). Behavioral tests including distant visual acuity (VA) and contrast sensitivity (CS), were measured every 5 min for 30 min. Results: Myopic defocus induced significantly greater rCBF increase in four cerebral regions compared with full correction: right precentral gyrus, right superior temporal gyrus, left inferior parietal lobule, and left middle temporal gyrus (P < 0.001). The differences were less significant in low myopes than emmetropes. In the hyperopic defocus session, the increased responses of rCBF were only observed in the right and left precentral gyrus. Myopic defocused VA and CS improved significantly within 5 min and reached a plateau shortly after. Conclusion: This study revealed that myopic defocus stimuli can significantly increase blood perfusion in visual attention-related cerebral regions, which suggests a potential direction for future investigation on the relationship between retinal defocus and its neural consequences.

Varying Dose of Atropine in Slowing Myopia Progression in Children Over Different Follow-Up Periods by Meta-Analysis.

Purpose: To evaluate the efficacy and safety of atropine for slowing myopia progression and to investigate whether the treatment effect remains constant with continuing treatment. Method: Studies were retrieved from MEDLINE, EMBASE, and the Cochrane Library from their inception to May 2021, and the language was limited to English. Randomized controlled trials (RCTs) and cohort studies involving atropine in at least one intervention and placebo/non-atropine treatment in another as the control were included and subgroup analysis based on low dose (0.01%), moderate dose (0.01%-<0.5%), and high dose (0.5-1.0%) were conducted. The Cochrane Collaboration and Newcastle-Ottawa Scale were used to evaluate the quality of RCTs and cohort studies, respectively. Results: Twelve RCTs and fifteen cohort studies involving 5,069 children aged 5 to 15 years were included. The weighted mean differences in myopia progression between the atropine and control groups were 0.73 diopters (D), 0.67 D, and 0.35 D per year for high-dose, moderate-dose, and low-dose atropine, respectively (χ2 = 13.76; P = 0.001, I 2 = 85.5%). After removing studies that provided extreme findings, atropine demonstrated a significant dose-dependent effect on both refractive change and axial elongation, with higher dosages of atropine resulting in less myopia progression (r = 0.85; P = 0.004) and less axial elongation (r = -0.94; P = 0.005). Low-dose atropine showed less myopia progression (-0.23 D; P = 0.005) and less axial elongation (0.09 mm, P < 0.001) in the second year than in the first year, whereas in high-dose atropine more axial elongation (-0.15 mm, P = 0.003) was observed. The higher dose of atropine was associated with a higher incidence of adverse effects, such as photophobia with an odds ratio (OR) of 163.57, compared with an OR of 6.04 for low-dose atropine and 8.63 for moderate-dose atropine (P = 0.03). Conclusion: Both the efficacy and adverse effects of atropine are dose-dependent in slowing myopia progression in children. The efficacy of high-dose atropine was reduced after the first year of treatment, whereas low-dose atropine had better efficacy in a longer follow-up period.

Astigmatism and its components in 12-year-old Chinese children: the Anyang Childhood Eye Study.

PURPOSE: To determine prevalence of refractive (RA), corneal (CA) and internal astigmatism (IA), including variation with gender and spherical equivalent refraction (SE), in a population of 12-year-old Chinese children. METHODS: A total of 1783 students with a mean age of 12.7 years (range 10.0-15.6 years) completed comprehensive eye examinations in the Anyang Childhood Eye Study. Data of cycloplegic refraction and corneal curvature were analysed. RESULTS: Prevalences of RA, CA and IA ≥1.0 D were 17.4% (95%CI 15.6% to 19.2%), 52.8% (50.5% to 55.1%)%) and 20.9% (19.0% to 22.8%), respectively. With different limits of astigmatism axes classification, including ±15°, ±20° and ±30°, RA and CA axes were mainly 'with-the-rule' (WTR) (ie, correcting axis of negative cylinders at or near 180°), while those for IA axes were mainly 'against-the-rule' (ATR) (ie, correcting axis of negative cylinders at or near 90°). RA was not different between the genders, but girls had higher prevalence and greater means of CA and IA. RA and CA increased in students with higher ametropia (more myopia and more hyperopia) and were the highest in a high myopic group (SE≤-6 D), while IA was stable across refraction groups. Children with RA higher than 0.50 D were more likely to have lens corrections (51%, 57%, 61% and 69% for magnitudes of ≥0.50 D, ≥0.75 D, ≥1.0 D and ≥1.5 D, respectively). CONCLUSIONS: Prevalence of RA in the Chinese 12-year-old children was relatively high compared with other studies. RA and CA had mainly 'WTR' astigmatism, while IA was mainly ATR and partially compensated for CA. Girls had greater means and prevalences of CA and IA than did boys. Both RA and CA, but not IA, increased with refractive errors away from emmetropia.

System Pharmacology-Based Strategy to Decode the Synergistic Mechanism of Zhi-zhu Wan for Functional Dyspepsia.

Functional dyspepsia (FD) is a widely prevalent gastrointestinal disorder throughout the world, whereas the efficacy of current treatment in the Western countries is limited. As the symptom is equivalent to the traditional Chinese medicine (TCM) term "stuffiness and fullness," FD can be treated with Zhi-zhu Wan (ZZW) which is a kind of Chinese patent medicine. However, the "multi-component" and "multi-target" feature of Chinese patent medicine makes it challenge to elucidate the potential therapeutic mechanisms of ZZW on FD. Presently, a novel system pharmacology model including pharmacokinetic parameters, pharmacological data, and component contribution score (CS) is constructed to decipher the potential therapeutic mechanism of ZZW on FD. Finally, 61 components with favorable pharmacokinetic profiles and biological activities were obtained through ADME (absorption, distribution, metabolism, and excretion) screening in silico. The related targets of these components are identified by component targeting process followed by GO analysis and pathway enrichment analysis. And systematic analysis found that through acting on the target related to inflammation, gastrointestinal peristalsis, and mental disorder, ZZW plays a synergistic and complementary effect on FD at the pathway level. Furthermore, the component CS showed that 29 components contributed 90.18% of the total CS values of ZZW for the FD treatment, which suggested that the effective therapeutic effects of ZZW for FD are derived from all active components, not a few components. This study proposes the system pharmacology method and discovers the potent combination therapeutic mechanisms of ZZW for FD. This strategy will provide a reference method for other TCM mechanism research.

Application of a strategy based on metabolomics guided promoting blood circulation bioactivity compounds screening of vinegar.

BACKGROUND: Rice vinegar (RV) and white vinegar (WV) as daily flavoring, have also used as accessory in traditional Chinese medicine processing. As we know, the promoting blood circulation efficiency could be enhanced when herbs processed by vinegar. Number of reports focused on health benefits derived by consumption of vinegar. However, few concerned the blood circulation bioactivity. METHODS: In this paper, a metabolomics guided strategy was proposed to elaborate on the chemical constituents' variation of two kinds of vinegar. GC-MS coupled with multivariate statistical analysis were conducted to analyze the chemical components in RV and WV and discriminate these two kinds of vinegar. The anti-platelet activities in vitro were investigated by whole blood aggregometry platelet test. And the anticoagulant activities were monitored by the whole blood viscosity, plasma viscosity, packed cell volume, prothrombin time, and four coagulation tests (PT, TT, APTT, FIB) in vivo. RESULTS: Constituents of RV and WV were globally characterized and 33 potential biomarkers were identified. The contents of four potential alkaloid biomarkers increased with aging time prolonged in RV. RV and its alkaloids metabolites exhibited some anti-platelet effects in vitro and anticoagulant activities in vivo. WV failed to exhibit promoting effects. CONCLUSIONS: Alkaloid metabolites were demonstrated to be the principal compounds contributing to discrimination and it increased with aging time prolonged in RV. RV exhibited the blood circulation bioactivity. The alkaloids of RV contributed to the blood circulation bioactivity. Graphical abstract The diagram of metabolomics guided promoting blood circulation bioactivity compounds screening strategy.

Long-Term Outcomes After Small-Bone-Window Posterior Fossa Decompression and Duraplasty in Adults with Chiari Malformation Type I.

BACKGROUND: Small-bone-window posterior fossa decompression with duraplasty is one of the popular surgical options for Chiari malformation type I, but its efficacy is controversial and the risk factors of clinical outcome remain unclear. METHODS: The study cohort included 152 patients with Chiari malformation type I who received small-bone-window posterior fossa decompression at Beijing Tiantan hospital from January 2008 to September 2009. All patients underwent combined surgical procedures: a small-bone-window suboccipital decompression (diameter, 2.5-3 cm) and a C1 laminectomy (1.5- to 2-cm wide) followed by a duraplasty with an autologous graft. Clinical manifestations, radiologic features, and follow-up data during a 6-year span were analyzed. Risk factors associated with outcome were investigated by the use of χ(2) analysis and logistic regression analysis. RESULTS: The average follow-up duration was 74 months. Symptoms were improved in 126 patients (82.9%), remained stable in 21 patients (13.8%), and deteriorated in 5 patients (3.3%). There was no mortality. Postoperative magnetic resonance imaging scans were available for all patients. Preoperatively, 112 patients were associated with syringomyelia, and the follow-up magnetic resonance images showed obvious reduction of syringomyelia in 73 patients (65.2%) and no significant change in 39 patients (34.8%). In addition, enlargement of the cistern magna was observed in 92 patients (85.2%). Regression analysis indicates preoperative motor dysfunction, brainstem herniation and basilar invagination may influence the clinical outcome (P < 0.05). CONCLUSIONS: Small-bone-window posterior fossa decompression with duraplasty is an effective and safe treatment option with a low complication rate. Motor dysfunction, brainstem herniation, and basilar invagination are predictors of poor clinical prognosis.