Impact of Online Video Game-Based Dichoptic Training on Binocular Vision Rehabilitation in Post-surgical Patients with Intermittent Exotropia.

INTRODUCTION: Dichoptic training has emerged as a promising rehabilitation approach for improving binocular visual function in patients with strabismus. A prospective observational study design was employed to assess the effectiveness of online video game-based dichoptic training in rehabilitating binocular visual function in patients who had undergone an operation for intermittent exotropia. METHODS: A total of 64 patients who had undergone an operation for intermittent exotropia were recruited and divided into the training group and the control group based on whether they would receive the dichoptic training. The dichoptic training was conducted for 3 months in the training group and the control group would not accept any form of orthoptic therapy. Assessments of binocular visual functions and deviation were conducted at baseline, 3-month and 6-month follow-up. RESULTS: Twenty-nine participants in the training group (mean 9.69 ± 2.66 years old) and 26 participants in the control group (mean 8.41 ± 2.64 years old) completed follow-up. At both 3- and 6-month follow-ups, the training group showed superior distance stereopsis compared to the control group, with near stereopsis only showing significant difference at the 6-month follow-up. Additionally, the training group exhibited significantly less distance exo-deviation drift than the control group at these times, and no significant difference was observed in near exo-deviation drift between the groups. The control group had a significantly higher rate of suboptimal surgical outcomes at both the 3- and 6-month follow-up. However, no significant differences were observed in simultaneous perception and fusion functions between the two groups. CONCLUSIONS: Online video game-based dichoptic training has the potential to become a novel postoperative rehabilitation strategy for patients with intermittent exotropia.

Critical role of transcriptome-wide m6A methylation in the aqueous humor of patients with pseudoexfoliation glaucoma.

N6-methyladenosine (m6A) modification is one of the most common types of methylation modifications in eukaryotic mRNA. However, its role in the pathogenesis of pseudoexfoliation glaucoma (PXG) has not yet been reported. To enhance understanding in this regard, we assessed the m6A methylome in the aqueous humor of patients with PXG. MeRIP-Seq and RNA-Seq analyses were performed to compare the m6A methylomes and gene expression profiles of the aqueous humor of patients with PXG with those of patients with age-related cataract (ARC). Colorimetric m6A quantification was performed to detect global m6A levels. Quantitative reverse transcription PCR confirmed the expression of m6A-related enzymes and mRNAs in both groups. Results showed significantly higher aqueous humor m6A levels in the PXG group than in the ARC group. Five m6A-related enzymes, including METTL3, YTHDC2, HNRNPA2B1, HNRNPC, and LRPPRC, were significantly up-regulated in PXG specimens. We also observed 9728 m6A-modified peaks related to 6126 gene transcripts in the PXG group, with more than 250 genes containing one m6A peak (hypomethylated or hypermethylated). The distribution of the m6A peaks was enriched in coding sequences and 3'-untranslated regions for both groups. GGAC motif structures were also significantly enriched. Bioinformatics analysis further revealed that m6A plays a critical role in extracellular matrix formation and histone deacetylation. Additionally, MMP14, ADAMTSL1, FN1, and HDAC1 showed significant changes in m6A methylation and mRNA expression in the PXG group. Therefore, m6A methylation may regulate extracellular matrix composition in PXG and METTL3 may be a pivotal regulator of this process. In the future, it would be necessary to investigate MMP14, ADAMTSL1, FN1, and HDAC1, which are potential target genes.

Surgical treatment versus observation in moderate intermittent exotropia (SOMIX): study protocol for a randomized controlled trial.

BACKGROUND: Intermittent exotropia (IXT) is the most common type of strabismus in China, but the best treatment and optimal timing of intervention for IXT remain controversial, particularly for children with moderate IXT who manifest obvious exodeviation frequently but with only partial impairment of binocular single vision. The lack of randomized controlled trial (RCT) evidence means that the true effectiveness of the surgical treatment in curing moderate IXT is still unknown. The SOMIX (surgical treatment versus observation in moderate intermittent exotropia) study has been designed to determine the long-term effectiveness of surgery for the treatment and the natural history of IXT among patients aged 5 to 18 years old. METHODS/DESIGN: A total of 280 patients between 5 and 18 years of age with moderate IXT will be enrolled at Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. After initial clinical assessment, all participants will be randomized to receive surgical treatment or observation, and then be followed up for 5 years. The primary objective is to compare the cure rate of IXT between the surgical treatment and observation group. The secondary objectives are to identify the predictive factors affecting long-term outcomes in each group and to observe the natural course of IXT. DISCUSSION: The SOMIX trial will provide important guidance regarding the moderate IXT and its managements and modify the treatment strategies of IXT. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02736526 . Registered April 13, 2016.

Effect of Proprioception and Balance Training Combined with Continuous Nursing on BBS Score and HSS Score of Patients Undergoing Total Knee Arthroplasty.

Background: Total knee arthroplasty is one of the most effective methods for the treatment of end-stage knee osteoarthritis, but 10% of patients still show insufficient function, strength, and mobility. Continuous nursing service plays an important role in the rehabilitation of patients undergoing total knee arthroplasty. For discharged and convalescent patients, the traditional follow-up model cannot solve the nursing problems of discharged patients. How to meet the health needs of discharged patients under the limited nursing resources has become an existing problem. Objective: To explore the effect of proprioception and balance training combined with continuous nursing on Berg balance scale (BBS) score and Hospital for Special Surgery (HSS) score of patients undergoing total knee arthroplasty (TKA) is the objective of this study. Methods: Sixty patients undergoing TKA in our hospital from December 2019 to April 2021 were enrolled. The patients were randomly assigned into the control group and the study group. The control group received continuous nursing, and the study group received proprioception and balance training combined with continuous nursing. Results: The nursing satisfaction of the study group was higher than that of the control group (P < 0.05). The HSS scores at discharge, 1 month, 3 months, and 6 months after discharge in the study group were higher than those in the control group (P < 0.05). It was higher in the study group than in the control group at 1 month, 3 months, and 6 months after discharge (P < 0.05). The pain catastrophizing score of the study group at discharge was lower than that of the control group at 1 month, 3 months, and 6 months after discharge (P < 0.05). The BBS scores at discharge, 1 month, 3 months, and 6 months after discharge in the study group were higher than those in the control group (P < 0.05). The Lindmark balance scores at discharge, 1 month, 3 months, and 6 months after discharge in the study group were lower than those in the control group (P < 0.05). Conclusion: Proprioception and balance training combined with continuous nursing can effectively promote the recovery of knee joint function of patients after TKA, enhance patients' pain catastrophizing grade, enhance patients' quality of life, effectively promote patients' knee joint function and BBS score, and promote the improvement of disease.

Novel Small Molecule Tyrosine Kinase 2 Pseudokinase Ligands Block Cytokine-Induced TYK2-Mediated Signaling Pathways.

A member of the Janus kinase (JAK) family, Tyrosine Kinase 2 (TYK2), is crucial in mediating various cytokine-signaling pathways such as interleukin-23 (IL23), interleukin-12 (IL12) and type I Interferons (IFN) which contribute to autoimmune disorders (e.g., psoriasis, lupus, and inflammatory bowel disease). Thus, TYK2 represents an attractive target to develop small-molecule therapeutics for the treatment of cytokine-driven inflammatory diseases. Selective inhibition of TYK2 over other JAK isoforms is critical to achieve a favorable therapeutic index in the development of TYK2 inhibitors. However, designing small molecule inhibitors to target the adenosine triphosphate (ATP) binding site of TYK2 kinase has been challenging due to the substantial structural homology of the JAK family catalytic domains. Here, we employed an approach to target the JAK homology 2 (JH2) pseudokinase regulatory domain of the TYK2 protein. We developed a series of small-molecule TYK2 pseudokinase ligands, which suppress the TYK2 catalytic activity through allosteric regulation. The TYK2 pseudokinase-binding small molecules in this study simultaneously achieve high affinity-binding for the TYK2 JH2 domain while also affording significantly reduced affinity for the TYK2 JAK homology 1 (JH1) kinase domain. These TYK2 JH2 selective molecules, although possessing little effect on suppressing the catalytic activity of the isolated TYK2 JH1 catalytic domain in the kinase assays, can still significantly block the TYK2-mediated receptor-stimulated pathways by binding to the TYK2 JH2 domain and allosterically regulating the TYK2 JH1 kinase. These compounds are potent towards human T-cell lines and primary immune cells as well as in human whole-blood specimens. Moreover, TYK2 JH2-binding ligands exhibit remarkable selectivity of TYK2 over JAK isoforms not only biochemically but also in a panel of receptor-stimulated JAK1/JAK2/JAK3-driven cellular functional assays. In addition, the TYK2 JH2-targeting ligands also demonstrate high selectivity in a multi-kinase screening panel. The data in the current study underscores that the TYK2 JH2 pseudokinase is a promising therapeutic target for achieving a high degree of biological selectivity. Meanwhile, targeting the JH2 domain represents an appealing strategy for the development of clinically well-tolerated TYK2 inhibitors that would have superior efficacy and a favorable safety profile compared to the existing Janus kinase inhibitors against autoimmune diseases.

Deep Learning-Based Classification of Cancer Cell in Leptomeningeal Metastasis on Cytomorphologic Features of Cerebrospinal Fluid.

Background: It is a critical challenge to diagnose leptomeningeal metastasis (LM), given its technical difficulty and the lack of typical symptoms. The existing gold standard of diagnosing LM is to use positive cerebrospinal fluid (CSF) cytology, which consumes significantly more time to classify cells under a microscope. Objective: This study aims to establish a deep learning model to classify cancer cells in CSF, thus facilitating doctors to achieve an accurate and fast diagnosis of LM in an early stage. Method: The cerebrospinal fluid laboratory of Xijing Hospital provides 53,255 cells from 90 LM patients in the research. We used two deep convolutional neural networks (CNN) models to classify cells in the CSF. A five-way cell classification model (CNN1) consists of lymphocytes, monocytes, neutrophils, erythrocytes, and cancer cells. A four-way cancer cell classification model (CNN2) consists of lung cancer cells, gastric cancer cells, breast cancer cells, and pancreatic cancer cells. Here, the CNN models were constructed by Resnet-inception-V2. We evaluated the performance of the proposed models on two external datasets and compared them with the results from 42 doctors of various levels of experience in the human-machine tests. Furthermore, we develop a computer-aided diagnosis (CAD) software to generate cytology diagnosis reports in the research rapidly. Results: With respect to the validation set, the mean average precision (mAP) of CNN1 is over 95% and that of CNN2 is close to 80%. Hence, the proposed deep learning model effectively classifies cells in CSF to facilitate the screening of cancer cells. In the human-machine tests, the accuracy of CNN1 is similar to the results from experts, with higher accuracy than doctors in other levels. Moreover, the overall accuracy of CNN2 is 10% higher than that of experts, with a time consumption of only one-third of that consumed by an expert. Using the CAD software saves 90% working time of cytologists. Conclusion: A deep learning method has been developed to assist the LM diagnosis with high accuracy and low time consumption effectively. Thanks to labeled data and step-by-step training, our proposed method can successfully classify cancer cells in the CSF to assist LM diagnosis early. In addition, this unique research can predict cancer's primary source of LM, which relies on cytomorphologic features without immunohistochemistry. Our results show that deep learning can be widely used in medical images to classify cerebrospinal fluid cells. For complex cancer classification tasks, the accuracy of the proposed method is significantly higher than that of specialist doctors, and its performance is better than that of junior doctors and interns. The application of CNNs and CAD software may ultimately aid in expediting the diagnosis and overcoming the shortage of experienced cytologists, thereby facilitating earlier treatment and improving the prognosis of LM.

The mediating role of coping in the relationship between family function and resilience in adolescents and young adults who have a parent with lung cancer.

PURPOSE: Resilience plays an important role in helping individuals to adapt to adversity and improve their psychosocial outcomes. This study aims to examine the mediating role of coping in the relationship between family function and resilience in adolescents and young adults (AYAs) who have a parent with lung cancer. METHOD: A total of 135 AYAs with a lung cancer parent were recruited from a tertiary grade A cancer center in southern China, and investigated using a self-designed general information questionnaire, the Resilience Scale for Chinese Adolescents, the Simplified Coping Style Questionnaire, and the Family Adaptation, Partnership, Growth, Affection, Resolve index. RESULTS: The mean score of AYAs' resilience was (3.61 ± 0.49), and its influencing factors included AYAs' years in work, family function, and positive coping. The total effect of family function on resilience was significant (total effect = 0.38, 95% CI [0.048-0.115]), and a positive indirect effect was identified for family function on resilience via positive coping (indirect effect = 0.10, 95% CI [0.005-0.043]). CONCLUSION: Family functioning can facilitate resilience either directly or by promoting positive coping. This study suggests that individualized interventions can be made to improve resilience by promoting family function, or by enhancing positive coping in AYAs with a lung cancer parent.

Newly developed abnormal head position and secondary esotropia after strabismus surgery for children with intermittent exotropia.

PURPOSE: To review cases of newly developed AHP and secondary esotropia (ET) after surgical correction for IXT. METHODS: Medical records of cases with newly developed AHP and secondary ET after surgical correction for IXT were retrospectively reviewed. RESULTS: Fifteen cases were included and the mean pre-operative exodeviation was 31.7 ± 10.6 prism diopters (PD) (range: 16-50) at distance. They received bilateral lateral rectus (LR) recessions (13/15), unilateral LR recession and medial rectus (MR) resection (1/15) or bilateral LR recession plus unilateral MR resection (1/15). Fourteen patients developed chin-down AHP with secondary V-pattern ET and 1 presented chin-up AHP with secondary A-pattern ET. The mean esodeviation in primary gaze was 22.7 ± 10.0 PD (range: 3-40) at distance. Twelve cases underwent a second surgery for correction of AHP and secondary ET, and approximately half (5/11) of the recessed LR muscles explored showed a 3-5 mm downward displacement of the new attachment. Surgical management mainly included advancement of LR to the original insertion with a 3-5 mm upward transposition. The AHP dissipated and ocular alignment returned to normal in all of these cases. Three cases did not require further surgery, and their AHP and secondary ET were no longer present at 2-5 months after the first surgery. CONCLUSION: A downward shift of the recessed LR in IXT may lead to secondary V-pattern ET and development of a chin-down AHP. Advancement of LR with an upward transposition serves as an effective procedure for the correction of this complication.

Discovery of spiro amide SHR902275: A potent, selective, and efficacious RAF inhibitor targeting RAS mutant cancers.

The RAS-RAF-MEK-ERK signaling pathway plays a key role to regulate multiple cellular functions. Acquired resistance to the first-generation RAF inhibitors that only targeted the bRAFV600E mutation prompted the need for a new generation of RAF inhibitors to target cancers bearing mutant RAS and wild type RAF activity by inhibition of paradoxical activation. Starting from the company's previously reported RAF inhibitor 1, extensive drug potency and drug-like properties optimizations led to the discovery of molecule 33 (SHR902275) with greatly improved in vitro potency and solubility. Molecule 33 exhibited good DMPK (Drug Metabolism and Pharmacokinetics) properties, excellent permeability, and outstanding mouse/rat oral PK. It was further evaluated in an in vivo RAS mutant Calu6 xenograft mouse model and demonstrated dose dependent efficacy. To achieve high exposure in a toxicity study, pro-drug 48 was also explored.

A Novel CD73 Inhibitor SHR170008 Suppresses Adenosine in Tumor and Enhances Anti-Tumor Activity with PD-1 Blockade in a Mouse Model of Breast Cancer.

INTRODUCTION: CD73 and adenosine support growth-promoting neovascularization, metastasis, and survival in cells, and promote anti-PD-1 mAb therapy-induced immune escape. Consequently, developing a CD73 inhibitor as monotherapy and a potential beneficial combination partner with immune-checkpoint inhibitors needs investigation. METHODS: CD73 inhibitors were evaluated in vitro with soluble and membrane-bound CD73 enzymes, as well as its PD biomarker responses in human peripheral blood mononuclear cells (PBMC) by flow cytometry and ELISA. The binding modes of the molecules were analyzed via molecular modeling. The anti-tumor activity and synergistic effect of SHR170008 in combination with anti-PD-1 mAb were evaluated in a syngeneic mouse breast cancer model. RESULTS: SHR170008 was discovered during the initial structural modifications on the link between the ribose and the α-phosphate of AMPCP, which significantly improved the stability of the compound confirmed by the metabolite identification study. Further modifications on the adenine base of AMPCP improved the potency due to forming stronger interactions with CD73 protein. It exhibited potent inhibitory activities on soluble and endogenous membrane-bound CD73 enzymes, and induced IFNγ production, reversed AMP-suppressed CD25+ and CD8+/CD25+ expression, and enhanced granzyme B production on CD8+ T cells in human PBMC. SHR170008 showed dose-dependent anti-tumor efficacy with suppression of adenosine in the tumors in EMT6 mouse breast tumor model. The increase of adenosine in tumor tissue by anti-PD-1 mAb alone was suppressed by SHR170008 in the combination groups. Simultaneous inhibition of CD73 and PD-1 neutralization synergistically enhanced antitumor immunity and biomarkers in response, and exposures of SHR170008 were correlated with the efficacy readouts. CONCLUSION: Our findings suggest that CD73 may serve as an immune checkpoint by generating adenosine, which suppresses the antitumor activity of anti-PD-1 mAb, and inhibition of CD73 may be a potential beneficial combination partner with immune-checkpoint inhibitors to improve their therapeutic outcomes in general.

Establishment and Verification of Neural Network for Rapid and Accurate Cytological Examination of Four Types of Cerebrospinal Fluid Cells.

Fast and accurate cerebrospinal fluid cytology is the key to the diagnosis of many central nervous system diseases. However, in actual clinical work, cytological counting and classification of cerebrospinal fluid are often time-consuming and prone to human error. In this report, we have developed a deep neural network (DNN) for cell counting and classification of cerebrospinal fluid cytology. The May-Grünwald-Giemsa (MGG) stained image is annotated and input into the DNN network. The main cell types include lymphocytes, monocytes, neutrophils, and red blood cells. In clinical practice, the use of DNN is compared with the results of expert examinations in the professional cerebrospinal fluid room of a First-line 3A Hospital. The results show that the report produced by the DNN network is more accurate, with an accuracy of 95% and a reduction in turnaround time by 86%. This study shows the feasibility of applying DNN to clinical cerebrospinal fluid cytology.

Crucial Impact of Hydrophilicity on the Self-Assembled 2D Colloidal Crystals Using Langmuir-Blodgett Method.

Large-scale close-packed two-dimensional (2D) colloidal crystal with high coverage is indispensable for various promising applications. The Langmuir-Blodgett (LB) method is a powerful technique to prepare 2D colloidal crystals. However, the self-assembly and movement of microspheres during the whole LB process are less analyzed. In this study, we clarify the crucial impact of hydrophilicity of the microspheres on their self-assembly in the LB process and on the properties of the prepared 2D colloidal crystals. The characteristic surface pressure-area isotherms of the microspheres have been analyzed and adjusted by only counting the quantity of the microspheres on the water surface, which leads to more accurate results. The critical surface pressures for hydrophilic and hydrophobic microspheres are about 61 and 46 mN/m, respectively. The decrease of the surface hydrophilicity of microspheres facilitates their self-assembly on the water surface, which further leads to higher coverage and less defects of the 2D colloidal crystals. A coverage of as high as 97% was obtained using hydrophobic microspheres. Entropy and intersphere capillary forces drive the self-assembly and transportation of the microspheres, respectively. Caused by the diffraction of visible light, opposite contrasts at local adjacent regions on the surface of the 2D colloidal crystals have been observed. The understanding of self-assembly of the microspheres during the LB process paves the way to fabricate the high-quality 2D colloidal crystals for various applications such as photonic papers and inks, stealth materials, biomimetic coatings, and related nanostructures.

Toward a Reliable Synaptic Simulation Using Al-Doped HfO2 RRAM.

The potential in a synaptic simulation for neuromorphic computation has revived the research interest of resistive random access memory (RRAM). However, novel applications require reliable multilevel resistive switching (RS), which still represents a challenge. We demonstrate in this work the achievement of reliable HfO2-based RRAM devices for synaptic simulation by performing the Al doping and the postdeposition annealing (PDA). Transmission electron microscopy and operando hard X-ray photoelectron spectroscopy results reveal the positive impact of Al doping on the formation of oxygen vacancies. Detailed I-V characterizations demonstrate that the 16.5% Al doping concentration leads to better RS properties of the device. In comparison with the other reported results based on HfO2 RRAM, our devices with 16.5% Al-doping and PDA at 450 °C show better reliable multilevel RS (∼20 levels) performance and an increased on/off ratio. The 16.5% Al:HfO2 sample with PDA at 450 °C shows good potentiation/depression characteristics with low pulse width (10 µs) along with a good On/Off ratio (>1000), good data retention at room temperature, and high temperature and good program/erase endurance characteristics with a pulse width of 50 ns. The synapse features including potentiation, depression, and spike time-dependent plasticity were successfully achieved using optimized Al-HfO2 RRAM devices. Our results demonstrate the beneficial effects of Al doping and PDA on the enhancement of the performances of RRAM devices for the synaptic simulation in neuromorphic computing applications.

Reliable resistive switching of epitaxial single crystalline cubic Y-HfO2 RRAMs with Si as bottom electrodes.

Previous studies have mainly focused on the resistive switching (RS) of amorphous or polycrystalline HfO2-RRAM. The RS of single crystalline HfO2 films has been rarely reported. Yttrium doped HfO2 (YDH) thin films were fabricated and successful Y incorporation into HfO2 was confirmed by x-ray photoemission spectroscopy. A pure cubic phase of YDH and an abrupt YDH/Si interface were obtained and verified by x-ray diffraction, Raman spectroscopy and transmission electron microscopy. A Pt/YDH/n++-Si heterostructure using Si as the bottom electrode was fabricated, which shows stable RS with an ON/OFF ratio of 100 and a reliable data retention (104 s). The electron transport mechanism was investigated in detail. It indicates that hopping conduction is dominating when the device is at a high resistance state, while space charge limited conduction acts as the dominant factor at a low resistance state. Such behavior, which is different from devices using TiN or Ti as electrodes, was attributed to the Y doping and specific YDH/Si interface. Our results demonstrate a proof of concept study to use highly doped Si as bottom electrodes along with single crystalline YDH as insulator layer for such RRAM applications as wireless sensors and synaptic simulation.

Long-term therapeutic outcome of ophthalmic complications following endoscopic sinus surgery.

Ophthalmic complications associated with endoscopic sinus surgery (ESS) are quite rare. There is a paucity of reliable data and limited experience on the clinical findings and treatments of these injuries. Our study here is to characterize the types of orbital injury following ESS, in particular extraocular muscle injury, and to evaluate the long-term therapeutic outcomes as compiled from a relatively large sample of Chinese patients.A series of 27 patients (21 males and 6 females; mean age = 42.6 years, ranges: 10-60 years) were retrospectively reviewed. The mean duration of orbital complication was 6.6 months (ranges: 1 day to 24 months). The right eye was affected in 19 patients and the left in 8 patients. All patients had various extraocular muscle dysfunction, including contusion, oculomotor nerve damage, muscle entrapment, muscle transection, and muscle destruction. All patients subjected to strabismus surgery showed an obvious reduction in deviation. Three patients achieved orthophoria without any surgery during the period of observation. All patients displayed mild to complicated orbital hemorrhage that often disappeared within 2 weeks. Optic nerve injury occurred in 29.6% of patients and vision damage in these patients was often irreversible.All patients with ophthalmic complications after ESS had strabismus and extraocular muscle dysfunction. Timing and type of strabismus surgery performed depended on the severity and number of muscles involved as well as the type of injury. This surgery is less effective in cases of restriction factor adhesion and/or entrapment as compared to that of patients with other types of strabismus. Orbital hemorrhages were usually resolved spontaneously, but optic nerve injury was mostly irreversible.

Single Stage Surgical Outcomes for Large Angle Intermittent Exotropia.

Although there were many prior studies about exotropia, few focused on large-angle intermittent exotropia. The goal of this study was to evaluate single-stage surgical outcomes for large-angle intermittent exotropia and analyze risk factors that may affect the success of surgery. Records from intermittent exotropia patients with exodeviations >60 prism diopters(PD) who were surgically treated at the Zhongshan Ophthalmic Center, of Sun Yat-Sen University were reviewed. Included within this review were data on, pre- and post-operative ocular motility, primary alignment, binocular vision and complications. Patients with exodeviations ≤70PD received two-muscle surgery, while those with exodeviations >70PD were subjected to a three-muscle procedure. A total of 40 records were reviewed. The mean exodeviation was 73±9PD at distance and 75±26PD at near. There were 25 patients received two-muscle surgery and 15 the three-muscle procedure. Orthophoria (deviation within 8PD) was obtained in 77.5% of these patients and the ratios of surgical under-correction and over-correction were 15% and 7.5% respectively. However, when combining ocular alignment with binocular vision as the success criteria, success rates decreased to 30%. No statistically significant differences in success rates were obtained between the two- and three-muscle surgery groups. Seven subjects experienced an abduction deficit during the initial postoperative stages, but eventually showed a full recovery. One patient required a second surgery for overcorrection. No statistically significant risk factors for poor outcome were revealed. Our data showed that single-stage two- and three-muscle surgeries for large-angle intermittent exotropia are effective in achieving a favorable outcome.

Clinical Characteristics and Surgical Outcomes in Patients With Intermittent Exotropia: A Large Sample Study in South China.

The clinical characteristics and surgical outcomes in a large sample of patients with intermittent exotropia (IXT) as well as an analysis of risk factors associated with surgical failures are presented in this article. Data from IXT patients who received surgical management at the Eye Hospital, in the Zhongshan Ophthalmic Center, of Sun Yat-Sen University, China from January 2009 to December 2013 were reviewed retrospectively. Included within this analysis were data from pre- and postoperative ocular motility, primary alignment, and binocular vision.A total of 1228 patients with IXT were reviewed. Males (50.4%) and females (49.6%) were nearly equally represented in this sample. Thirty-two patients (2.6%) had a family history of strabismus. The mean age at onset was 6.77  ±â€Š 6.43 years (range 7 months -48.5 years), mean duration at presentation was 7.35  ±â€Š 6.68 years (range 6 months-47 years), and mean age at surgery was 13.7  ±  8.8 years (range 3-49 years). The mean refractive error was -0.84  ±â€Š 2.69 diopter in the right eye and -0.72  ±â€Š 2.58 diopter in the left eye. Amblyopia (4.2%), oblique muscle dysfunction (7.0%), and dissociated vertical deviation (4.7%) were also present in these patients. The most common subtype of IXT was the basic type (88.1%). Orthophoria was observed in 80.5% of patients and the ratios of surgical undercorrection and overcorrection were 14.7% and 4.8%, respectively, as determined with a mean follow-up time of 7.8  ±â€Š 3.7 months. When combining ocular alignment with binocular vision as the success criteria, the success rate decreased to 35.6%. Multivariate risk factor analysis showed that only the loss of stereoacuity (P = 0.002) was associated with a poor outcome. There were no differences in the long-term results between bilateral lateral rectus recession and unilateral lateral rectus recession with medial rectus resection.Most IXT patients displayed normal vision, with few having positive family histories, amblyopia, oblique muscle dysfunction, and dissociated vertical deviation. The most common subtype of IXT was the basic type. Long-term surgical results were less favorable when sensory status was included in the criteria for success. Patients with stereoacuity loss were at an increased risk for poor outcomes.

Discovery of aminoquinazoline derivatives as human A(2A) adenosine receptor antagonists.

Novel bicyclic adenosine A(2A) antagonists with an aminoquinazoline moiety were designed and synthesized. The optimization of the initial lead compound based on in vitro and in vivo activity has led to the discovery of a potent and selective class of adenosine A(2A) antagonists. The structure-activity relationships of this novel series of bicyclic aminoquinazoline derivatives as adenosine A(2A) antagonists are described in detail.

[Effect of high glucose on NADPH oxidase expression and reactive oxygen species generation in human umbilical vein endothelial cells].

OBJECTIVE: To explore the effect of high glucose on NADPH oxidase (NOX) expression and intracellular reactive oxygen species (ROS) generation in human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were divided into a control group, a mannite group, a glucose group and a glucose plus diphenylene iodonium (DPI) group. Intracellular ROS was detected by flow cytometry. RNA and protein expression of NOX in HUVECs was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. RESULTS: 1) Compared with the control group, the intracellular ROS were significantly increased in the glucose group (P< 0.05, n=3), but there were no significant change in the glucose plus DPI group (P> 0.05, n=3); 2) Compared with the control group, the mRNA and protein expression of NOX4 in the glucose group were significantly increased (P< 0.05), but there were no significant change in the mRNA and protein expression of NOX2, p22phox, p67phox and rac (all P> 0.05); 3) there were no significant difference in the mRNA and protein expression of NOX2, NOX4, p22phox, p67phox and rac between the glucose plus DPI group and the control group (all P> 0.05). CONCLUSION: High glucose may increases intracellular ROS generation by increasing the expression of NOX4 in HUVECs, which might mediate the oxidative stress.