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Saeed Aljohani,1 Jingyun Wang,2 Mitchell Scheiman,3 Qing-Qing Tan,4 Hongxin Xu,5 Nawaf Almutairi,1 Saleh Alshammeri1 1Department of Optometry, College of Applied Medical Science, Qassim University, Buraydah, Qassim, Saudi Arabia; 2SUNY College of Optometry, New York, NY, USA; 3Salus University, Wyncote, PA, USA; 4Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 5Panorama Windows Ltd, New York, NY, USACorrespondence: Saeed Aljohani, Email sa.aljohani@qu.edu.saBackground: Previous studies have shown that it is necessary to evaluate adherence during the treatment process, using educational intervention methods which have been shown to improve adherence with patching treatment. A previous study reported that an educational cartoon had significantly improved adherence with patching. However, this black-white cartoon is not commercially available.Objective: This study investigates the feasibility of a 4-minute educational cartoon video in improving adherence with patching therapy for amblyopic children.Methods: Children (3 to 10 years old) with unilateral amblyopia who were prescribed 2 hours or 6 hours of patching per day were enrolled. Objective adherence to the treatment was tracked using a microsensor. Children returned after 4 weeks ± 2 days to measure adherence. Participants with adherence ≤ 50% were eligible to watch the educational cartoon video. They continued with the previously prescribed treatment (2 hours or 6 hours patching) for an additional week to evaluate the follow-up adherence.Results: A total of 27 participants were enrolled. The mean age (SD) was 6.6 (1.5) years. Twenty-two participants (12 in the 2 hours patching group and 10 in the 6 hours patching group) had adherence ≤ 50% and watched our cartoon video. The cartoon video improved mean adherence (SD) from 29.6% (11.9%) to 56.8% (12.1%) in all 22 participants from both regimens (paired 2-tailed t-test, t= − 11, P < 0.000).Conclusion: The Educational cartoon video is feasible for use in a clinical setting. These data showed a trend of improvement in adherence with both patching regimens in children after watching the educational cartoon video.Keywords: educational cartoon, amblyopia, adherence, patching

Xuan Yue,1,&ast; Xiao-Ming Liu,1,&ast; Jiao Chen,1,&ast; Hai-Yun Chen,2 Qian-Qian Tan,2 Yong Zhou2 1Department of Neurology, XuZhou Children’s Hospital, XuZhou, People’s Republic of China; 2Puluo (Wuhan) Medical Biotechnology Co., LTD, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Ming Liu, Department of Neurology, XuZhou Children’s Hospital, Sudi North Road, No. 18, XuZhou, JiangSu, People’s Republic of China, Tel +18952173923, Email xzlrlxm@163.comObjective: The third generation of antiepileptic medication (ASM) perampanel (PER), is mostly used as an add-on treatment for refractory epilepsy patients, and rarely used as a monotherapy. This study aims to observe the efficacy and assess the cognitive effects of PER monotherapy in patients with self-limited epilepsy with centrotemporal spikes (SeLECTS).Patients and Methods: Through screening, 86 patients who were first diagnosed with SeLECTS and treated with PER monotherapy were included in this study. All patients were followed up at least 12 months, and Evaluated the efficacy and safety of PER by observing the seizures of patients. At the same time, we used the P300 event-related potential (ERP) component and Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) to evaluate the cognitive changes in children before and after treatment with PER.Results: Ten percent of the children experienced adverse effects, such as dizziness, gait instability, and irritability. The drug retention rate at the last follow-up was 98.83%. Further more, the P300 ERP component and WISC-IV tests were performed no significant difference before and 12 months after PER monotherapy in SeLECTS children.Conclusion: The third-generation of ASM PER monotherapy had a clear effect in children with SeLECTS. A small dose of PER can control seizures well and has no obvious effect on cognitive development.Keywords: self-limited epilepsy with centrotemporal spikes, P300 ERP component, Wechsler Intelligence Scale for Children-Fourth Edition, perampanel, monotherapy

Saeed Aljohani,1 Sulaiman Aldakhil,1 Saif H Alrasheed,2,3 Qing-Qing Tan,4 Saleh Alshammeri1 1Department of Optometry, College of Applied Medical Sciences, Qassim University, Buraydah, Qassim, Saudi Arabia; 2Department of Optometry, College of Applied Medical Sciences, Qassim University, Qassim, Buraydah, Saudi Arabia; 3Department of Binocular Vision, Faculty of Optometry and Visual Sciences, Al-Neelain University, Khartoum, Sudan; 4Department of Ophthalmology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of ChinaCorrespondence: Saif H Alrasheed, Department of Optometry, College of Applied Medical Sciences, Qassim University, P.O.Box 6688, Qassim, Buraydah, Saudi Arabia, Tel +966505201475, Fax +966-16-3800050, Email s.rasheed@qu.edu.saPurpose: To provide the clinical characteristics of amblyopia in children under 17 years of age in Qassim Region, Saudi Arabia.Patients and Methods: The study was a cross-sectional hospital-based, included 121 children with amblyopia aged between 3 and 17 years, referred from 6 hospitals in Qassim region to the paediatric optometry clinic at Qassim University medical city. Demographics and comprehensive ocular examination including visual acuity (VA), assessment of anterior and posterior segment, cycloplegic refraction (RE), angle of deviation, and cause of amblyopia were collected.Results: The mean age at diagnosis of amblyopia was 8.93 ± 3.67 years. The leading cause of amblyopia was strabismus and anisometropia shared the same percentage at 29.75%, and the combined-mechanism at 18.18%. Amblyopia was more common in males 57.85%, particularly strabismic amblyopia in 66.67% and anisometropic amblyopia in 61.11%, p = 0.408. Amblyopia was more predominant in the age group 6- to 9-year-old, particularly, strabismic amblyopia 44.44%, and amblyopia due to a combined mechanism of 36.36%, p = 0.066. The degree of hyperopia was not varied by the cause of amblyopia (P = 0.401), with slightly high hyperopia found in ametropic and strabismic amblyopia. Conversely, hyperopic astigmatism was significantly associated with amblyopia P = 0.020, with a high degree of hyperopic astigmatism found in meridional amblyopia and ametropic amblyopia.Conclusion: The commonest types of amblyopia in children were attributed to strabismus and anisometropia. Causes of amblyopia differed by age group with strabismus, anisometropia, and combined mechanism accounting for most children aged 6- to 9-years and strabismus for children aged less than 6 years. Hyperopic and myopic astigmatism were significantly associated with anisometropia and meridional amblyopia. Therefore, efforts should be made for early diagnosis and management of childhood amblyopia and uncorrected refractive errors to avoid their impact on quality of life.Keywords: amblyopia, anisometropic amblyopia, meridional amblyopia, Saudi Arabia, hyperopic astigmatism, uncorrected refractive errors, visual impairment

Purpose: To evaluate and compare the effect of decentration and tilt on the optical quality of monofocal and trifocal intraocular lenses (IOL)., Methods: Optical quality of a monofocal IOL (AcrySof IQ SN60WF; Alcon Laboratories, Inc., USA) and a trifocal IOL (AcrySof IQ PanOptix; Alcon Laboratories, Inc., USA) was assessed using an in vitro optical bench (OptiSpheric IOL R&D; Trioptics GmbH, Germany). At apertures of 3.0 mm and 4.5 mm, modulation transfer function (MTF) at spatial frequency of 50 lp/mm, MTF curve and the United States Air Force (USAF) resolution test chart of the two IOLs were measured and compared at their focus with different degrees of decentration and tilt. Optical quality at infinity, 60 cm and 40 cm and the through-focus MTF curves were compared when the two IOLs were centered at apertures of 3.0 mm and 4.5 mm. Spectral transmittance of the two IOLs was measured by the UV-visible spectrophotometer (UV 3300 PC; MAPADA, China)., Results: The SN60WF and the PanOptix filtered blue light from 400 to 500 nm. Both IOLs at the far focus and the PanOptix at the intermediate focus showed a decrease in optical quality with increasing decentration and tilt. The PanOptix demonstrated enhanced optical quality compared to the previous gradient at the near focus at a decentration range of 0.3-0.7 mm with a 3.0 mm aperture, and 0.5 mm with a 4.5 mm aperture, whereas other conditions exhibited diminished optical quality with increasing decentration and tilt at the focus of both IOLs. When the two IOLs were centered, the SN60WF had better optical quality at infinity, while the PanOptix had better optical quality at 60 cm and 40 cm defocus. The optical quality of the SN60WF exceeded that of the PanOptix at far focus, with a 3 mm aperture decentration up to 0.7 mm and a 4.5 mm aperture decentration up to 0.3 mm; this observation held true for all tilts, irrespective of aperture size. As both decentration and tilt increased, the optical quality of the SN60WF deteriorated more rapidly than that of the PanOptix at the far focal point., Conclusions: The SN60WF showed a decrease in optical quality with increasing decentration and tilt. Optical quality of the PanOptix at the near focus increased in some decentration conditions and decreased in some conditions, while it showed a decrease at the other focuses with increasing decentration. While tilt only had a negative effect on optical quality. When both IOLs were centered, the PanOptix provided a wider range of vision, while the SN60WF provided better far distance vision. At the far focus, the SN60WF has better resistance to tilt than the PanOptix, but the optical quality degrades more quickly when decentered and tilted., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Non-small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (EGFR) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with EGFR ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified. Hence, we conducted this study tofind correlations between the tumor immune microenvironment of EGFR ex20ins and the efficacy of ICI-combined regimen., Methods: We performed single-cell transcriptome sequencing and multiplex immunofluorescence staining (mIF) to investigate the immune microenvironment of NSCLC patients with EGFR ex20ins, L858R, and EGFR wild-type. We analyzed 15 treatment-naïve NSCLC samples utilizing single-cell RNA sequencing (scRNA-seq). Another 30 cases of EGFR L858R and 4 cases of wild-type were recruited to compare the immune microenvironment with that of EGFR ex20ins (28 cases) by mIF., Results: We observed that cell components, function and interactions varied between EGFR ex20ins, L858R, and wild-type NSCLC.We discovered similar T cell and CD8+ T cell distributions among groups but found noninferior or even better T cell activation in ex20ins patients. Infiltrating CD8+ FOXP3- T cells were significantly lower in the tumor region of EGFR ex20ins compared to wild-type. T cells from the ex20ins group had a greater tendency to promote cancer cell inflammation and epithelial-mesenchymal transition (EMT) compared to wild-type group. For macrophages, there were more M2-like macrophages in ex20ins patients. M1-like macrophages in ex20ins group produced fewer antitumor cytokines than in other groups., Conclusions: The immune microenvironment of EGFR ex20ins is more suppressive than that of L858R and wild-type, suggesting that ICI monotherapy may not be sufficient for these patients. ICI-combined regimen might be a treatment option for EGFR ex20ins due to tumor-promoting inflammation and noninferior T cell functions in the immune microenvironment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ferroptosis is a novel form of cell death, which is distinguished from apoptosis and necrosis, and characterized by accumulation of lipid-based reactive oxygen species (ROS) in an iron-dependent manner. Erastin, a small molecule, was widely reported to trigger ferroptosis in various kinds of cancer cells, including pancreatic cancer cells by inducing ROS accumulation. However, how erastin treatment exerts cytotoxicity is not still fully understood. In this study, the effects of erastin in causing pancreatic cancer cell death via inducing ferroptosis and apoptosis are investigated. As expected, erastin treatment caused ROS accumulation, increase in iron concentration and non-apoptotic cell death, which is different from that of induced by apoptosis inducer, staurosporine. Interestingly, erastin treatment caused the upregulation of clusterin, which contributes to the regulation of malignant behaviors of pancreatic cancer, including preventing apoptosis and inducing chemoresistance. Without erastin treatment, overexpressed clusterin significantly promoted cell proliferation, which is consistent with its cytoprotective roles. After erastin treatment, overexpressed clusterin decreased erastin-induced ROS accumulation and cell death. By measuring iron concentration, reduced glutathione (GSH) and glutathione peroxidase 4 (GPX4), it is revealed that clusterin caused resistance to erastin-induced ferroptosis potentially via maintaining the enzymatic activity of GPX4, without disturbing GSH amount. Thus, ferroptosis inducer, erastin, may crosstalk with apoptotic cell death via regulating clusterin, indicating a more complex regulatory network between ferroptosis and apoptosis., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Despite intensive studies in modeling neuropsychiatric disorders especially autism spectrum disorder (ASD) in animals, many challenges remain. Genetic mutant mice have contributed substantially to the current understanding of the molecular and neural circuit mechanisms underlying ASD. However, the translational value of ASD mouse models in preclinical studies is limited to certain aspects of the disease due to the apparent differences in brain and behavior between rodents and humans. Non-human primates have been used to model ASD in recent years. However, a low reproduction rate due to a long reproductive cycle and a single birth per pregnancy, and an extremely high cost prohibit a wide use of them in preclinical studies. Canine model is an appealing alternative because of its complex and effective dog-human social interactions. In contrast to non-human primates, dog has comparable drug metabolism as humans and a high reproduction rate. In this study, we aimed to model ASD in experimental dogs by manipulating the Shank3 gene as SHANK3 mutations are one of most replicated genetic defects identified from ASD patients. Using CRISPR/Cas9 gene editing, we successfully generated and characterized multiple lines of Beagle Shank3 (bShank3) mutants that have been propagated for a few generations. We developed and validated a battery of behavioral assays that can be used in controlled experimental setting for mutant dogs. bShank3 mutants exhibited distinct and robust social behavior deficits including social withdrawal and reduced social interactions with humans, and heightened anxiety in different experimental settings (n = 27 for wild-type controls and n = 44 for mutants). We demonstrate the feasibility of producing a large number of mutant animals in a reasonable time frame. The robust and unique behavioral findings support the validity and value of a canine model to investigate the pathophysiology and develop treatments for ASD and potentially other psychiatric disorders., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To investigate the effect of the optional biometric parameters lens thickness (LT) and center corneal thickness (CCT) in the Kane formula on intraocular lens (IOL) power calculation., Methods: A cross-sectional study included consecutive cataract patients who received uncomplicated cataract surgery with IOL implantation from May to September 2022 were enrolled. The ocular biometric parameters were obtained using IOLMaster 700 and then inputted into online Kane formula calculator. The IOL power was calculated for targeting emmetropia and compared between groups: not omitting (NO) group, omitting LT and CCT (OLC) group, omitting LT (OL) group and omitting CCT (OC) group. Further, according to the axial length (AL), anterior chamber depth (ACD), and mean keratometry (Km), the eyes were divided into three subgroups, respectively., Results: 1005 eyes of 1005 consecutive patients were included. There was no significant difference in IOL power between NO group and OC group (P = 0.064), and the median absolute difference (MedAD) was 0.05D. The IOL power in NO group showed significant differences from OLC group and OL group respectively (P < 0.001), and both MedAD values were 0.18D. Among AL subgroups, MedAD ranged from 0.06D to 0.35D in short eyes. Among ACD subgroups, the above values ranged from 0.06D to 0.23D in shallow ACD subgroup. Among Km subgroups, these values ranged from 0.05D to 0.31D in steep Km subgroup., Conclusion: The optional biometric parameter CCT has no effect on the calculation results of the Kane formula, whereas the parameter LT has a great influence on the Kane formula results for the IOL power calculation in cataract patients with short AL, shallow ACD and steep Km., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To determine the effectiveness of the Convergence Insufficiency Symptom Survey (CISS) in evaluating visual symptoms in young adults with convergence excess (CE)., Methods: A cross-sectional study was performed based on a population of optometry students. Comprehensive binocular vision tests including cover test, near point of convergence, fusional vergence and accommodative amplitude, were performed. Participants were categorised into three groups: normal binocular vision (NBV), CE and CE + accommodative insufficiency (AI) (i.e., CE + AI). The CISS was administered to each participant. An analysis of variance with Bonferroni correction was performed to compare clinical measures among the three groups. A receiver-operating characteristic (ROC) curve was constructed to evaluate the ability of CISS to differentiate CE from the NBV population., Results: A total of 181 participants were enrolled, including 96 in the NBV group, 66 in the CE group and 19 in the CE + AI group. A significant difference in CISS score was detected between the three groups (p < 0.001). Post-hoc tests showed significantly higher CISS scores in the CE group (16.7 ± 10.8) and the CE + AI group (19.7 ± 10.9) compared with the NBV group (12.2 ± 7.8) (p = 0.01 and p = 0.005, respectively), with no difference between the CE and the CE + AI groups (p = 0.52). The ROC curve showed the CISS poorly (but significantly) differentiated CE from NBV (area under the curve = 0.62, p = 0.01). The optimal cutoff value for a CISS score to differentiate CE was 16, with sensitivity and specificity of 52% and 72%, respectively., Conclusions: Young adults with CE had significantly higher CISS scores than those with NBV. Although using the CISS solely for diagnosing CE is not recommended, it can be used to provide a measure of symptoms in individuals identified as having CE based on clinical measurements., (© 2023 College of Optometrists.)

Aim: To investigate the effect of all-trans retinoic acid (ATRA) on retinol dehydrogenase 5 (RDH5), matrix metalloproteinase-2 (MMP-2) and transforming growth factor-β2 (TGF-β2) transcription levels, and the effect of RDH5 on MMP-2 and TGF-β2 in retinal pigment epithelium (RPE) cells., Methods: After adult RPE cell line-19 (ARPE-19 cells) intervened with gradient concentrations of ATRA (0-20 µmol/L) for 24h, flow cytometry was used to detect the proliferation and apoptosis of cells in each group, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect RDH5, MMP-2 and TGF-β2 mRNA expression. Then, after ARPE-19 cells transfected with three different siRNA targets for 48h, the RDH5 knockdown efficiency of each group and expression of MMP-2 and TGF-β2 mRNA within them was detected by qRT-PCR., Results: Flow cytometry results showed that ATRA could inhibit the proliferation of RPE cells and promote the apoptosis of RPE cells, and the difference of apoptosis was statistically significant when the ATRA concentration exceeded 5 µmol/L and compared with the normal control group ( P =0.027 and P =0.031, respectively). qRT-PCR results showed that ATRA could significantly inhibit the expression level of RDH5 mRNA ( P <0.001) and promote the expression of MMP-2 and TGF-β2 mRNA ( P =0.03 and P <0.001, respectively) in a dose-dependent manner, especially when treated with 5 µmol/L ATRA. The knockdown efficiency of RDH5 siRNA varies with different targets, among which RDH5 siRNA-435 had the highest knockdown efficiency, i.e. , more than 50% lower than that of the negative control group ( P =0.02). When RDH5 was knocked down for 48h, the results of qRT-PCR showed that the expressions of MMP-2 and TGF-β2 mRNA were significantly up-regulated ( P <0.001)., Conclusion: ATRA inhibits the expression of RDH5 and promotes MMP-2 and TGF-β2, and further RDH5 knockdown significantly upregulates MMP-2 and TGF-β2. These findings suggest that RDH5 may be involved in an epithelial-mesenchymal transition of RPE cells mediated by ATRA., (International Journal of Ophthalmology Press.)

Purpose: To define the prognostic role of lymph node involvement (LNI) in patients with pancreatic neuroendocrine tumors (PNETs) and identify predictors of LNI using a comprehensive multifactor analysis focusing on preoperative radiological features., Methods: This study included 236 patients with preoperative computed tomography who underwent radical surgical resection of PNETs at our hospital between 2009 and 2019. Univariate and multivariable logistic regression analyses were performed to investigate the risk factors associated with LNI and tumor recurrence. The disease-free survival (DFS) rates with and without LNI were compared., Results: Forty-four of the 236 patients (18.6%) had LNI. Biliopancreatic duct dilatation (odds ratio [OR], 2.295; 95% confidence interval [CI], 1.046-5.035; p = 0.038), tumor margin (OR, 2.189; 95% CI, 1.034-4.632; p = 0.041), and WHO grade (G2: OR, 2.923; 95% CI, 1.005-8.507; p = 0.049; G3: OR, 12.067; 95% CI, 3.057-47.629; p < 0.001) were independent risk factors of LNI in PNETs. Multivariable analysis showed that LNI (OR, 2.728; 95% CI, 1.070-6.954; p = 0.036), G3 (OR, 4.894; 95% CI, 1.047-22.866; p = 0.044), and biliopancreatic duct dilatation (OR, 2.895; 95% CI, 1.124-7.458; p = 0.028) were associated with PNET recurrence in patients after surgery. Patients with LNI had a significantly worse DFS than those without LNI (3-year DFS: 85.9 vs. 96.7%; p < 0.001; 5-year DFS: 65.1 vs. 93.9%; p < 0.001)., Conclusion: LNI was associated with decreased DFS. Biliopancreatic duct dilatation, irregular tumor margins, and grades G2 and G3 were independent risk factors for LNI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Femtosecond transient absorption, nanosecond transient absorption, and nanosecond resonance Raman spectroscopy techniques coupled with density functional theory calculations were performed to unravel the photocyclization and photorelease mechanisms of a diarylethene based compound ( 1o ) containing two caged groups (OMe and OAc). Since the ground state parallel (P) conformer of 1o with a large dipole moment is stable in DMSO, the fs-TA transformations observed for 1o in DMSO mainly have contributions from the P conformer, which undergoes an intersystem crossing to generate a corresponding triplet state species. In a less polar solvent like 1,4-dioxane, in addition to the P path behavior of 1o , an antiparallel (AP) conformer can also take place to give a photocyclization reaction from the Franck-Condon state and finally give a deprotection via this pathway. This work provides a deeper understanding for these reactions, which not only facilitate the applications of diarylethene compounds but also help for the future design of functionalized diarylethene derivatives for particular applications.

Background: Pancreatic neuroendocrine tumors (pNETs) are heterogenous neoplasms, of which the prognosis varies widely. Purely cystic pancreatic neuroendocrine tumors (C-pNETs) are a small subset of pNETs in which data are extremely rare. This study aimed to compare clinicopathological and long-term survival differences between C-pNETs and solid pNETs (S-pNETs)., Methods: A retrospective review of 242 patients with pNETs underwent resection in our institution from 2009 to 2019 was conducted. Demography characteristics, clinicopathological features and long-term outcomes of them were analyzed., Results: Sixteen out of 242 patients (6.6%) were identified as C-pNETs. Compared with S-pNETs, C-pNETs were more frequently non-functional (75% vs 45%, P = 0.02), and the median tumor diameter of C-pNETs was smaller (36 mm vs. 47 mm, P = 0.001). And the accuracy of preoperative diagnosis of C-pNETs was significantly lower (31% vs 78%, P = 0.001). Of note, the majority of C-pNETs were well-differentiated with G1 (81% vs 35%, P = 0.001). And there were no G3 (0 vs 7%, P = 0.001) in C-pNETs. No T4 stage or R1/R2 surgical margin detected in C-pNETs. And only one C-pNETs (6%) had regional lymph node metastasis (N) or synchronous distant metastasis (M). Additionally, only one patient with C-pNETs (6%) suffered tumor recurrence, compared with 24 (13%) for S-pNETs. And survival analysis showed the patients with C-pNETs seemed to be with better disease-free survival (P = 0.26)., Conclusion: C-pNETs are rare subtype with possibly less aggressive behavior comparing with their solid counterparts. Recurrence and tumor-related death still occurs in patients with resected C-pNETs, although they tend to be with more favorable prognosis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: For patients with lung malignancies with RET rearrangement, the efficacy of immune checkpoint inhibitors is limited. The characteristics of the tumour immune microenvironment (TIME) and molecular pathological features of these patients have not been well elucidated. We aimed to investigate their clinical outcomes and explore characteristics of TIME, using multiplex immunohistochemistry technology (mIHC)., Patients and Methods: The pathology and TIME characteristics of 29 patients with lung malignancies with RET rearrangement were retrospectively analysed, and their relationships with clinical efficacy and prognosis were investigated. Gene detection relied on high-throughput sequencing, and TIME detection was based on mIHC., Results: Of 29 patients, 25(86%) had adenocarcinoma, and the acinar type accounted for the greatest percentage of patients, followed by the solid type, regardless of whether the disease was early or locally advanced and metastatic. In addition, we report a novel KIF5B-RET(k24:R8) rearrangement in pulmonary sarcoma. The density of CD8+ T cells in tumour stroma in early-stage patients was significantly higher than that in locally advanced and metastatic patients (P = 0.014). The proportion of M2 macrophages in tumour stroma was significantly higher than that in tumour parenchyma (P = 0.046). Although the difference was not statistically significant (P = 0.098), patients positive for M2 macrophage infiltration into the tumour parenchyma (≥5%) may have a better prognosis. Seven patients received immunotherapy and disease control rate was 85.7%., Conclusions: A novel KIF5B-RET rearrangement variant in pulmonary sarcoma shows similar TIME characteristics to lung cancer. amongst patients with lung malignancies with RET rearrangement, patients with M2 macrophage infiltration into the tumour parenchyma may have a better prognosis, but further studies with larger cohorts are needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To compare the binocular vision status of patients pre- and post-cataract surgery, and to investigate the risk factors for patients who develop binocular vision anomalies post-surgery., Methods: A prospective study of patients (≥50 years) who elected to undergo bilateral cataract surgery was implemented. A comprehensive binocular vision test battery including stereopsis, ocular alignment, fusional vergence, vergence facility, near point of convergence and the Convergence Insufficiency Symptom Survey (CISS) was administered before the first surgery and at the third visit after surgery on the second eye. A detailed diagnostic classification protocol was applied to identify the presence of binocular vision anomalies pre- and post-surgery., Results: Seventy-three participants were included at baseline, 24 (33%) of whom were diagnosed with non-strabismic binocular vision anomalies (NSBVA), mainly convergence insufficiency (18/73, 25%). Fifty-one participants completed the post-operative evaluation, 17 (33%) of whom had NSBVA pre-surgery and 13 (26%) post-surgery (p = 0.48). There were a number of conversions from NSBVA to normal binocular vision and vice versa. Logistic regression showed that the adjusted odds ratio of pre-existing NSBVA diagnosis for predicting the risk of post-operative NSBVA was 6.37 (p < 0.01). There were no significant changes in most binocular vision measures post-surgery, except for a significant improvement in the CISS score (p < 0.01, Cohen's d = 0.83)., Conclusions: Binocular vision anomalies, especially convergence insufficiency, are prevalent in the age-related cataract population. Cataract surgery does not appear to be a significant risk factor for the development of new binocular vision anomalies. A pre-existing binocular vision anomaly is the main risk factor for predicting a post-operative binocular vision anomaly in this population., (© 2022 College of Optometrists.)

Purpose: To evaluate the repeatability of wavefront aberration measurements and the correlation between corneal aberration and pupil size in normal eyes using a wavefront-based autorefractor (i.Profiler Plus ; Carl Zeiss Vision, Germany)., Methods: A prospective cross-sectional study. Wavefront aberrations, including spherical aberration (SA) (Z 4 0 ), coma (Z 3 -1 , Z 3 1 ), trefoil (Z 3 -3 , Z 3 3 ) and total higher-order aberrations (tHOA), were measured at different pupil diameters. The repeatability was evaluated using one-way ANOVA method, and statistical indicators including within-subject standard deviation (S w ), test-retest repeatability (TRT), and intra-class correlation coefficient (ICC). The correlations between corneal aberrations and pupil sizes were evaluated by Pearson correlation analysis., Results: A total of 96 healthy young volunteers were enrolled. Corneal and ocular higher-order aberrations (HOA) measured by i.Profiler showed S w  < 0.01 μm, TRT < 0.10 μm, ICC > 0.90. There was a linear positive correlation between the corneal HOA and pupil size. The correlation coefficient between SA and tHOA was the largest (r = 0.996, P < 0.001)., Conclusions: The measurements of wavefront aberrations by i.Profiler are highly repeatable. Corneal HOA was significantly dependent on pupil size. SA was the most influential aberration for visual quality in this study., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Tumor-related osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia. The diagnosis of TIO can be very difficult because of its nonspecific nature of clinical manifestations. Here we reported a case of young TIO patient with "painful knee joint with difficulty in moving" to improve the clinical diagnosis and treatment levels., Case Presentation: The patient's clinical features were consistent with TIO. A tumor was successfully located in left tibial by 68 Ga-DOTATATE PET/CT, and then was surgically resected. Upon pathologic assessment, the tumor was diagnosed as phosphaturia stromal tumor (PMT) with positive Vim staining. After the surgery, serum phosphate level rapidly recovered and symptoms significantly improved., Conclusion: TIO should be considered in patients with chronically hypophosphorus osteomalacia in the setting of no family history. Early removal of the responsible tumors is clinically essential for the treatment, and imaging examination is of great significance for tumor localization., (© 2022. The Author(s).)

Background: Tic disorders (TDs), including Tourette syndrome, are childhood-onset neuropsychiatric disorders characterized by motor and/or vocal tics that commonly affect children's physical and mental health. The pathogenesis of TDs may be related to abnormal neurotransmitters in the cortico-striatal-thalamo-cortical circuitry, especially dopaminergic, glutamatergic, and serotonergic neurotransmitters. The purpose of this study was to preliminarily investigate the differences in the three types of neurotransmitters in plasma and urine between children with TD and healthy children., Methods: We collected 94 samples of plasma and 69 samples of urine from 3-12-year-old Chinese Han children with TD before treatment. The plasma and urine of the same number of healthy Chinese Han children, matched for age and sex, participating in a physical examination, were collected. Ultra-performance liquid chromatography-tandem mass spectrometry was used to detect the three types of neurotransmitters in the above samples., Results: The plasma levels of norepinephrine, glutamic acid, and γ-aminobutyric acid, and the urine levels of normetanephrine and 5-hydroxyindoleacetic acid were higher in the TD children than in healthy children. The area under the curve (AUC) values of the above neurotransmitters in plasma and urine analyzed by receiver operating characteristic curve analysis were all higher than 0.6, with significant differences. Among them, the combined AUC of dopamine, norepinephrine, normetanephrine, glutamic acid, and γ-aminobutyric acid in the 8-12-year-old subgroup was 0.930, and the sensitivity and specificity for TD were 0.821 and 0.974, respectively ( p = 0.000)., Conclusions: There are differences in plasma and urine neurotransmitters between TD children and healthy children, which lays a foundation for further research on the pathogenesis of TD.

Background: This study is the first part of the "Binocular Vision Anomalies after Cataract Surgery" study that aimed to investigate the impact of cataract surgery on binocular vision status in adults with age-related cataract. This study aimed to investigate the preoperative binocular vision status of participants with age-related cataract., Methods: Patients who elected to undergo bilateral cataract surgery (≥50 years of age) were recruited. Clinical measures of binocular vision including stereopsis, ocular alignment, fusional vergence, vergence facility, convergence amplitude and a symptom survey related to binocular vision anomalies were administered. A detailed classification protocol was established to identify the presence of binocular vision anomalies. The frequency of specific binocular vision anomalies and normative data of binocular vision measures were reported., Results: A total of 73 subjects were evaluated. No strabismus was detected in the cohort. Non-strabismic binocular vision anomalies were detected in 24 subjects (32.9%), of whom 18 (24.7%) had convergence insufficiency, 3 (4.1%) had basic exophoria, 2 (2.7%) had convergence excess, and 1 (1.4%) had fusional vergence dysfunction. Decreased vergence facility and convergence amplitude were more common compared to the pre-presbyopes (P < 0.01)., Conclusion: Binocular vision problems, especially convergence insufficiency, are common in the adults with age-related cataract. The study results demonstrate that the lack of normative binocular vision data for the presbyopic population is a significant gap in the literature and suggest the need for a study of normative data for this population., Trial Registration: The study was registered at ClinicalTrials.gov (NCT03592615, USA)., (© 2022. The Author(s).)

Backgroud: Tumor grade is the determinant of the biological aggressiveness of pancreatic neuroendocrine tumors (PNETs) and the best current tool to help establish individualized therapeutic strategies. A noninvasive way to accurately predict the histology grade of PNETs preoperatively is urgently needed and extremely limited., Methods: The models training and the construction of the radiomic signature were carried out separately in three-phase (plain, arterial, and venous) CT. Mann-Whitney U test and least absolute shrinkage and selection operator (LASSO) were applied for feature preselection and radiomic signature construction. SVM-linear models were trained by incorporating the radiomic signature with clinical characteristics. An optimal model was then chosen to build a nomogram., Results: A total of 139 PNETs (including 83 in the training set and 56 in the independent validation set) were included in the present study. We build a model based on an eight-feature radiomic signature (group 1) to stratify PNET patients into grades 1 and 2/3 groups with an AUC of 0.911 (95% confidence intervals (CI), 0.908-0.914) and 0.837 (95% CI, 0.827-0.847) in the training and validation cohorts, respectively. The nomogram combining the radiomic signature of plain-phase CT with T stage and dilated main pancreatic duct (MPD)/bile duct (BD) (group 2) showed the best performance (training set: AUC = 0.919, 95% CI = 0.916-0.922; validation set: AUC = 0.875, 95% CI = 0.867-0.883)., Conclusions: Our developed nomogram that integrates radiomic signature with clinical characteristics could be useful in predicting grades 1 and 2/3 PNETs preoperatively with powerful capability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Qiu, Tan, Chen, Tan, Ren, Yang, Yao, Cao, Ke and Liu.)

KCNQ5 is suggestively associated with myopia, but its specific role in the myopic process has not been studied further. The aim of this study was to investigate the expression of potassium channel gene KCNQ5 and the changes of K + microenvironment within the retina of form deprivation myopia (FDM) guinea pigs. A total of 60 guinea pigs were randomly divided into the normal control (NC) group, the self-control (SC) group, and the form-deprivation (FD) group for different treatments. Molecular assays and immunohistochemistry (IHC) were conducted to measure the expression and distribution of KCNQ5-related gene and protein in the retina. We determined the K + concentration in the retina. In addition, the possible effects of form deprivation on potassium ionic currents and the pharmacological sensitivity of KCNQ5 activator Retigabine and inhibitor XE991 to the M-current in RPE cells were investigated using the patch-clamp technique. As a result, FD eyes exhibited more myopic refraction and longer AL. The mRNA and protein levels of KCNQ5 significantly decreased in the FD eyes, but the K + concentration increased. In addition, the M-type K + current [IK (M) ] density decreased in FD RPE cells, and were activated or inhibited in a concentration-dependent manner due to the addition of Retigabine or XE991. Overall, KCNQ5 was significantly downregulated in the retina of FD guinea pigs, which may be associated with the increasing K + concentration, decreasing IK (M) density, and elongating ocular axis. It suggested that KCNQ5 may play a role in the process of myopia, and the intervention of potassium channels may contribute to the prevention and control of myopia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Tan, Lan, Lv, Zhou, Zhong, Gu, Mao and Liao.)

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders that is featured by the extensive deposition of fat in the hepatocytes. Current treatments are very limited due to its unclear pathogenesis. Here, we investigated the function of circ&#95;0057558 and miR-206 in NAFLD. High-fat diet (HFD) feeding mouse was used as an in vivo NAFLD model and long-chain-free fatty acid (FFA)-treated liver cells were used as an in vitro NAFLD model. qRT-PCR was used to measure levels of miR-206, ROCK1 mRNA, and circ&#95;0057558, while Western blotting was employed to determine protein levels of ROCK1, p-AMPK, AMPK, and lipogenesis-related proteins. Immunohistochemistry were performed to examine ROCK1 level. Oil-Red O staining was used to assess the lipid deposition in cells. ELISA was performed to examine secreted triglyceride (TG) level. Dual-luciferase assay was used to validate interactions of miR-206/ROCK1 and circ&#95;0057558/miR-206. RNA immunoprecipitation was employed to confirm the binding of circ&#95;0057558 with miR-206. Circ&#95;0057558 was elevated while miR-206 was reduced in both in vivo and in vitro NAFLD models. miR-206 directly bound with ROCK1 3'-UTR and suppressed lipogenesis and TG secretion through targeting ROCK1/AMPK signaling. Circ&#95;0057558 directly interacted with miR-206 to disinhibit ROCK1/AMPK signaling. Knockdown of circ&#95;0057558 or overexpression of miR-206 inhibited lipogenesis, TG secretion and expression of lipogenesis-related proteins. ROCK1 knockdown reversed the effects of circ&#95;0057558 overexpression. Injection of miR-206 mimics significantly ameliorated NAFLD progression in vivo. Circ&#95;0057558 acts as a miR-206 sponge to de-repress the ROCK1/AMPK signaling and facilitates lipogenesis and TG secretion, which greatly contributes to NAFLD development and progression., (© 2021. The Author(s).)

Significance: This study confirmed the application of the Convergence Insufficiency Symptom Survey (CISS) in distinguishing children with oculomotor dysfunction (OMD) from those with normal binocular vision (NBV) but not in distinguishing children with accommodative insufficiency (AI)., Purpose: The purpose of this study was to determine the application of the CISS for quantifying symptoms in children aged 9 to 18 years with AI or OMD., Methods: All participants (aged 9 to 18 years) underwent comprehensive binocular vision tests including visual acuity, cover test, near point of convergence, fusional vergence, accommodative amplitude, and the Developmental Eye Movement test to ascertain the presence of any vision conditions. According to the examination outcomes, participants were divided into four groups: NBV group, AI group, OMD group, and a group with both AI and OMD (AI-OMD). The CISS was individually administered to each participant. An ANOVA and a receiver operating characteristic curve were performed to evaluate the ability of the CISS to quantify symptoms in AI and OMD., Results: A total of 82 participants were qualified for this study, with 18 in the NBV group, 21 in AI, 16 in OMD, and 27 in AI-OMD group. The mean CISS score was significantly different among the four groups (F = 4.19, P = .008). Post hoc tests showed significantly higher CISS scores in the OMD group than the NBV (P = .01) and the AI (P = .03) groups, but no differences were detected among other groups. Receiver operating characteristics curve showed a significant effect of the CISS score on predicting an OMD (area under curve = 0.78, P = .006). Using a CISS score of ≥15, good discrimination of OMD was obtained., Conclusions: Children with OMD (Developmental Eye Movement type II or IV) had higher CISS scores than ones with NBV. Using the CISS, children with AI did not report worse symptoms than children with NBV., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Aim: To compare the visual performance of pseudophakic eyes implanted with A1-UV and SN60WF aspheric intraocular lens (IOL), and to investigate the correlations between visual quality parameters and pupil size., Methods: This prospective comparative study included 105 eyes of 90 patients with age-related cataract who underwent uneventful phacoemulsification. The subjects were divided into two groups according to the implanted IOL type. Three months postoperatively, visual acuity and contrast sensitivity were measured, wave-front aberrations were assessed using a KR-1W aberrometer (Topcon), and objective optical quality parameters were performed using an optical quality analysis system-OQAS II (Visiometrics). Independent sample t -test and Spearman correlation analysis were used for data analysis., Results: There were no significant differences found in visual acuity, contrast sensitivity and visual quality parameters between the two groups ( P >0.05). The measured intraocular spherical aberration (SA) in A1-UV IOL eyes of -0.19±0.05 µm was close to the designed SA value of -0.20 µm. The modulation transfer function cutoff, Strehl ratio and OQAS values were negatively correlated with pupil size in both groups ( P <0.01)., Conclusion: The subjective and objective visual quality in pseudophakic eyes with A1-UV and SN60WF IOLs are comparable. For aspheric IOL eyes, visual quality decreases with increasing pupil size., (International Journal of Ophthalmology Press.)

The genus of Coelogyne Lindl. comprised about 200 species while its generic relationship has been uncertain. The whole chloroplast genome of C. barbata was reported in order to provide new data on the molecular phylogeny of Coelogyne . The cp genome of C. barbata was 1,600,93 bp in total length, including a pair of inverted repeat regions (IR, 26,710 bp), one large single-copy region (LSC, 87,868 bp), and one small single-copy region (SSC, 188,05 bp). The complete chloroplast DNA encoded 132 genes, containing 86 protein-coding genes, 38 tRNA genes, and eight rRNA genes. Phylogenetic analysis showed that C. barbata was related to Pholidota imbricata ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Purpose: To investigate the impact of different sizes of steep meridian clear corneal incisions for phacoemul sification on anterior corneal higher-order aberrations., Methods: Medical records of patients who underwent 2.2-mm coaxial micro-incision cataract surgery or 2.75-mm coaxial small-incision cataract surgery were retrospectively reviewed. Only patients with preexisting anterior corneal astigmatism <2.00 diopters (D) and ≥0.50 D who underwent a steep meridian clear corneal incision were included. Primary outcomes were 3rd- to 6th-order anterior corneal higher-order aberrations with an 8-mm pupil. Anterior corneal astigmatism and effective phaco time were evaluated as secondary outcomes. Preoperative and 3-month postoperative outcomes were evaluated., Results: Anterior corneal astigmatism significantly decreased after both procedures; however, there was no significant difference found in surgically induced anterior corneal astigmatism between the two procedures (p=0.146). Although the total higher-order aberrations did not significantly change after both procedures, the group comparison showed a significant difference in surgically induced total higher-order aberrations (a decrease of 0.337 ± 1.156 mm in 2.2-mm coaxial micro-incision cataract surgery and an increase of 0.106 ± 0.521 mm in 2.75-mm coaxial small-incision cataract surgery, p=0.046). Spherical aberrations significantly decreased after 2.2-mm coaxial micro-incision cataract surgery (p=0.001), whereas they did not change significantly after 2.75-mm coaxial small-incision cataract surgery (p=0.564). Coma did not significantly change after either of the procedures. Trefoil did not significantly change after 2.2-mm coaxial micro-incision cataract surgery (p=0.361), whereas it significantly increased after 2.75-mm coaxial small-incision cataract surgery (p<0.001). There was no significant difference shown in effective phaco time between the procedures. A significantly positive correlation was shown between surgically induced anterior corneal astigmatism and coma in 2.75-mm coaxial small-incision cataract surgery (r=0.387, p=0.006). There was no significant correlation found between any surgically induced higher-order aberration changes and effective phaco time., Conclusions: The results showed that 2.2-mm coaxial micro-incision cataract surgery and 2.75-mm coaxial small-incision cataract surgery did not significantly degrade the total higher-order aberrations of the anterior cornea. However, the surgically induced changes in total higher-order aberration showed a significant difference between the two procedures, with a slight reduction after 2.2-mm coaxial micro-incision cataract surgery and a slight increase after 2.75-mm coaxial small-incision cataract surgery. Phaco time and power used during surgery had no impact on corneal aberrations.

Background: Owing to the limited prevalence and heterogeneity, it is difficult to predict long-term survival of non-functional pancreatic neuroendocrine tumours (NF-PNETs).This study aimed to evaluate the factors predicting disease-specific survival (DSS) for well-differentiated NF-PNETs., Methods: Data were collected retrospectively from 256 patients with pancreatic neuroendocrine tumours who underwent surgical resection between January 2009 and December at our institution. Of these, 103 NF-PNETs (40%) were identified for analysis., Results: Of the 103 patients, 54 were male (52%) and the mean age was 52 years (range 21-75 years). Most patients (60/103, 58%) in our series were symptomatic. Seventeen patients (16%) died during follow-up, with a median period of 47 months. There were 88 patients with well-differentiated tumours and 10 of them (10/88, 11%) died of tumour progression. Median DSS after primary resection was 58.8 months (range 16-122 months). Multivariate analysis identified age >52 years (P = 0.038) and tumour grade G2 (P = 0.001) as statistically significant predictors of DSS. There was no association between gender, tumour size, symptoms, surgical procedure, severe complications, tumour location, tumour size, resection margin, positive lymph nodes and vascular invasion with DSS., Conclusion: Tumour grade, age, presence of symptoms and distant metastasis were related to poor DSS of NF-PNETs. Age >52 years and tumour grade G2 might be independent predictors of poor DSS for patients with well-differentiated NF-PNETs., (© 2020 Royal Australasian College of Surgeons.)

Although pancreatic neuroendocrine tumors (PNETs) are generally considered to have a favorable overall prognosis after resection, disease recurrence has been observed. Few studies have specifically addressed recurrence after resection of PNETs, especially for non-functioning PNETs (NF-PNETs). The aim of our study is to analyze the recurrence of resected well-differentiated NF-PNETs.Patients who underwent surgical resection for grade 1 and 2 NF-PNETs without synchronous metastasis were identified for analysis. Patients were treated from January 2009 to December 2017 in our institution. Univariate and multivariate cox regression analysis were conducted to identify prognostic factors.Of the 88 patients, 46 were men (52%) and the mean age was 52 years. With a median follow-up of 49.1 months (range, 8-122 months), there were 12 recurrences (14%). Liver was the most common recurrence site (7/12, 58%). The 1-, 3-, and 5-year recurrence-free survival was 99%, 90%, and 88%, respectively. Univariate analysis identified that age >52 years, positive lymph nodes, tumor grade 2, and Ki67 index ≥5% were statistically significant. Multivariate analysis identified that Ki67 index ≥5% (hazard ratio [HR], 4.69; 95% confidence interval [CI], 1.36-16.75, P = .015), positive lymph nodes (HR, 6.75; 95% CI, 1.73-24.43, P = .006) were independently associated with recurrence. The 5-year disease-free survival rate was 53% (95% CI, 14.20-91.81%) for patients with Ki-67 ≥5% or (and) positive lymph nodes, while 95% (95% CI, 82.26-100%) for the patients without these 2 factors.Ki67 index and lymph node status are independently associated with recurrence after resection of well-differentiated NF-PNETs in this study.

The resistances of matrix protein 2 (M2) protein inhibitors and neuraminidase inhibitors for influenza virus have attracted much attention and there is an urgent need for new drug. The antiviral drugs that selectively act on RNA polymerase are less prone to resistance and possess fewer side effects on the patient. Therefore, there is increased interest in screening compounds that can inhibit influenza virus RNA polymerase. Three natural compounds were found by using molecular docking-based virtual screening, which could bind tightly within the polymerase acidic protein-polymerase basic protein 1 (PA-PB1) subunit of influenza virus polymerase. Firstly, their drug likeness properties were evaluated, which showed that the hepatotoxicity values of all the three compounds indicating they had less or no hepatotoxicity, and did not have the plasma protein biding (PPB) ability, the three compounds needed to be modified in some aspects, like bulky molecular size. The stability of the complexes of PA-hits was validated through molecular dynamics (MD) simulation, revealing compound 2 could form more stable complex with PA subunit. The torsional conformations of each rotatable bond of the ligands in PA subunit were also monitored, to investigate variation in the ligand properties during the simulation, compound 3 had fewer rotatable bonds, indicating that the molecule had stronger rigidity. The bar charts of protein-ligand contacts and contacts over the course of trajectory showed that four key residues (Glu623, Lys643, Asn703 and Trp706) of PA subunit that participated in hydrogen-bond, water bridge and hydrophobic interactions with the hit compounds. Finally, the binding free energy and contributed energies were calculated by using MM-GBSA method. Out of the three compounds, compound 1 showed the lowest total binding free energy. Among all the interactions, the contribution of the covalent binding and the van der Waals energy were more than other items, compound 1 formed more stable hydrogen bonds with the residues of PA subunit binding pocket. This study smoothed the path for the development of novel lead compounds with improved binding properties, high drug likeness, and low toxicity to humans for the treatment of influenza, which provided a good basis for further research on novel and effective influenza virus PA-PB1 interaction inhibitors., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest associated with the publication of this manuscript., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDA) is one of the most serious causes of death in the world due to its high mortality and inefficacy treatments. MEX3A was first identified in nematodes and was associated with tumor formation and may promote cell proliferation and tumor metastasis. So far, nothing is known about the relationship between MEX3A and PDA., Methods: In this study, the expression level of MEX3A in PDA tissues was measured by immunohistochemistry. The qRT-PCR and western blot were used to identify the constructed MEX3A knockdown cell lines, which was further used to construct mouse xenotransplantation models. Cell proliferation, colony formation, cell apoptosis and migration were detected by MTT, colony formation, flow cytometry and Transwell., Results: This study showed that MEX3A expression is significantly upregulated in PDA and associated with tumor grade. Loss-of-function studies showed that downregulation of MEX3A could inhibit cell growth in vitro and in vivo. Moreover, it was demonstrated that knockdown of MEX3A in PDA cells promotes apoptosis by regulating apoptosis-related factors, and inhibits migration through influencing EMT. At the same time, the regulation of PDA progression by MEX3A involves changes in downstream signaling pathways including Akt, p-Akt, PIK3CA, CDK6 and MAPK9., Conclusions: We proposed that MEX3A is associated with the prognosis and progression of PDA,which can be used as a potential therapeutic target., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

This prospective cross-sectional study aimed to evaluate the agreement of two new biometers for measuring ocular biometric parameters in young healthy eyes. Ocular biometric parameters were measured using IOLMaster 700 and OA-2000. Power vector analyses of Cartesian (J0) and oblique (J45) components of corneal astigmatism were performed. The right eyes of 103 healthy volunteers were analyzed. The 95% limits of agreement ranged from -0.03 to 0.03 mm, -0.08 to 0.07 mm, -0.18 to 0.18 diopters (D), -1.09 to 1.16 D, -1.18 to 1.15 D for axial length (AL), anterior chamber depth (ACD), mean keratometry, J0 and J45 respectively, which were all comparable between the two biometers, while significant differences were detected in lens thickness (LT), central corneal thickness (CCT), white-to-white (WTW) and pupil diameter (PD). Predicted intraocular lens (IOL) powers were comparable between the two biometers by Haigis and Barrett Universal II formulas, while not by SRK/T, Hoffer Q and Holladay 2. Excepting CCT, WTW and PD meaurements, IOLMaster 700 and OA-2000 have excellent agreement on ocular biometric measurements and astigmatism power vectors, which provides more options for ocular biometric measurements and enables constant optimization for IOL power calculation.

Purpose: To investigate whether optical quality could be improved by cylindrical correction for low astigmatic eyes with different amounts and axis orientations in patients with myopia up to - 3.00 diopters (D)., Methods: A cross-sectional study enrolling healthy young eyes with 0 to - 3.00 D myopia and - 0.50 to - 0.75 D myopic astigmatism was implemented. With a repeated-measures design, outcome measures were sequentially obtained for each subject under two correction modalities: spherocylindrical correction and spherical correction. Subjective refraction was used to determine the refractive prescriptions accordingly in the two correction modalities to obtain optimal subject-reported visual acuity. Primary outcomes were optical quality parameters including objective scatter index (OSI), modulation transfer function (MTF) cut-off, Strehl ratio (SR), and a simulated contrast visual acuity-optical quality analysis system (OQAS) values (OV) obtained by a double-pass system. Corrected distance visual acuity (CDVA) was measured as a secondary outcome. Outcome comparisons between the two correction modalities were performed by grouping in different amounts (- 0.50 D, - 0.75 D) and axes (with the rule, WTR; against the rule, ATR; oblique, OBL) of astigmatism., Results: A total of 194 eyes of 194 subjects were evaluated. Significantly better CDVA were shown by spherocylindrical correction for all types of astigmatism except for - 0.50 D WTR astigmatism (P = 0.831). For eyes with - 0.50 D WTR astigmatism, better outcome was only shown in OSI with spherocylindrical correction (P = 0.019). For eyes with - 0.50 D ATR and OBL astigmatism, spherocylindrical correction demonstrated better outcomes in all parameters except for SR (P > 0.05). For eyes with - 0.75 D astigmatism, significantly better outcomes in all optical quality parameters were shown with spherocylindrical correction regardless of the axis (P < 0.05)., Conclusions: Eyes with ATR or OBL myopic astigmatism may benefit in optical quality and visual acuity by combining a cylindrical correction even with a low amount down to - 0.50 D. However, optical quality and visual acuity improvement are limited for WTR astigmatic eyes when the amount of astigmatism is less than - 0.75 D.

Objective: To investigate refractive error development in preterm children with severe retinopathy of prematurity (ROP) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and laser photocoagulation., Methods: Selection criteria were comparative studies that compared the refractive errors in children, birthweights ≤1500 grams and gestational ages ≤30 weeks, and treatments for Type I ROP with intravitreal bevacizumab (IVB) versus laser photocoagulation. Studies were identified using PubMed, Google Scholar, and published reviews. Meta-analyses were performed on the post-treatment outcomes of spherical equivalent (SEQ), cylindrical power, and prevalence of high myopia. Longitudinal development of refractive error in IVB, or in laser-treated children, or in normal full-term children was visually summarized., Results: Two randomized controlled trials and 5 non-randomized studies, including a total of 272 eyes treated by IVB and 247 eyes treated by laser, were included in this study. Compared with laser-treated children, IVB-treated children have less myopic refractive error (P<0.001), lower prevalence of high myopia (P<0.05), and less astigmatism (P = 0.02)., Conclusions: Treatment with IVB is associated with less myopia and astigmatism than laser treatment for infants with severe ROP. Given the complexity of ROP and the variability of dosing, our review supports close monitoring of refractive error outcomes in children treated with IVB., Competing Interests: The authors have declared that no competing interests exist.

Genome-wide association studies (GWAS) of myopia and refractive error have generated exciting results and identified novel risk-associated loci. However, the interpretation of the findings of GWAS of complex diseases is not straightforward and has remained challenging. This review provides a brief summary of the main focus on the advantages and limitations of GWAS of myopia, with potential strategies that may contribute to further insight into the genetics of myopia in the post-GWAS or omics era.

Background: To compare the postoperative optical quality in eyes with customized selection and random selection of aspheric intraocular lens (IOL) implantation., Methods: A prospective, nonrandomized study was implemented in adult cataract patients who underwent unilateral phacoemulsification with aspheric IOL implantation. Patients were allocated into two treatment groups: a customized group and a control group. In the customized group, the aspheric IOL selection was based on the corneal spherical aberration to enable the postoperative target ocular spherical aberration closest to zero; in the control group, the aspheric IOLs were chosen using a random strategy. Primary outcome measurements included the following objective optical quality assessments: higher-order aberrations obtained by a Hartmann-shack aberrometer at 4 mm and 6 mm pupil diameters; objective scatter index (OSI), modulation transfer function (MTF) cut-off, Strehl ratio (SR) and a simulated contrast visual acuity-optical quality analysis system value (OV) obtained by a double-pass system with a 4-mm aperture. Subjective visual acuity was measured as secondary outcome. All the patients were followed up for 3 months., Results: Eighty-four patients in the customized group and 78 patients in the control group were evaluated. There was no significant difference in postoperative visual acuity between the two groups (P > 0.05). Significantly less ocular higher-order aberrations were shown in the customized group (P < 0.05). No significant difference was shown in OSI, MTF cut-off, SR and OV between the two groups (P > 0.05)., Conclusions: Although customized selection of aspheric IOL implantation showed less postoperative ocular aberrations, it performed similarly to random selection of aspheric IOL implantation in terms of postoperative visual acuity, simulated contrast visual acuity, intraocular scatter, modulation transfer function and Strehl ratio., Trial Registration: Retrospectively registered on 07/06/2019. Registration number: ChiCTR1900024356 .

Two new species of Parastephanellus Enderlein, 1906 (Hymenoptera: Stephanidae) are described and illustrated from China: P. evexus Tan van Achterberg, sp. n. and P. yixiwui Tan van Achterberg, sp. n. The male of P. brevicoxalis Hong, van Achterberg Xu, 2011, is described and the supposed male by Chen et al. (2016) is included in P. evexus. Parastephanellus austrochinensis Belokobylskij, 1995, (former synonym of P. brevistigma Enderlein, 1913) is reinstated. A new key to the species of Parastephanellus Enderlein from China is provided and all species are illustrated.

The local structures for various Rh 2+ centers in AgCl are theoretically studied using density functional theory (DFT) with periodic CP2K program. Through geometry optimizing, the stable ground states with minimal energies and electronic structures are obtained for the tetragonally elongated (T E ), orthorhombically elongated (O E ), and tetragonally compressed (T C ) centers, and the corresponding g and hyperfine coupling tensors are calculated in ORCA level. The calculations reveal obvious Jahn-Teller elongation distortions of about 0.109 and 0.110 Å along [001] axis for T E and O E centers without and with 1 next nearest neighbor (nnn) cation vacancy V Ag in [100] axis, respectively. Whereas T C center with 1 nnn V Ag along [001] axis exhibits moderate axial compression of about 0.066 Å due to the Jahn-Teller effect. For O E and T C centers with 1 nnn V Ag , the ligand intervening in the central Rh 2+ and the V Ag is found to displace away from the V Ag by about 0.028 and 0.024 Å, respectively. The present results are discussed and compared with those of the previous calculations based on the perturbation formulas by using the improved ligand field theory., (Copyright © 2017 John Wiley & Sons, Ltd.)

Temperate insects have evolved diapause, a period of programmed developmental arrest during specific life stages, to survive unfavourable conditions. During the diapause preparation phase (DPP), diapause-destined individuals generally store large amounts of fat by regulating nutrition distribution for the energy requirement during diapause maintenance and postdiapause development. Although nutritional patterns during the DPP have been investigated at physiological and biochemical levels in many insects, it remains largely unknown how nutritional metabolism is regulated during the DPP at molecular levels. We used RNA sequencing to compare gene expression profiles of adult female cabbage beetles Colaphellus bowringi during the preoviposition phase (POP) and the DPP. Most differentially expressed genes were involved in specific metabolic pathways during the DPP. Genes related to lipid and carbohydrate metabolic pathways were clearly highly expressed during the DPP, whereas genes related to protein metabolic pathways were highly expressed during the POP. Hormone challenge and RNA interference experiments revealed that juvenile hormone via its nuclear receptor methoprene-tolerant mediated the expression of genes associated with nutritional metabolism during the DPP. This work not only sheds light on the mechanisms of diapause preparation, but also provides new insights into the molecular basis of environmental plasticity in insects., (© 2017 The Royal Entomological Society.)

Four new species of Trigonalyidae are described and illustrated from Qinling Mts (Shaanxi, NW China): Bareogonalos xibeidai Tan & van Achterberg, sp. n. , Jezonogonalos mandibularis sp. n. , J. shaanxiensis sp. n. , and Taeniogonalos paraclypeata sp. n. Orthogonalys hirasana Teranishi, 1929, is re-instated and reported from China. The female of Taeniogonalos alticola (Tsuneki, 1991) is described for the first time. In total, 18 species are known from Shaanxi province, 20 species for NW China, and eight described species are newly recorded for Shaanxi: Jezonogonalos luteata Chen et al., 2014, Orthogonalys hirasana Teranishi, 1929, O. elongata Teranishi, 1929, Pseudogonalos hahnii (Spinola, 1840), Taeniogonalos alticola (Tsuneki, 1991), T. formosana (Bischoff, 1913), T. taihorina (Bischoff, 1914), and Teranishia glabrata Chen et al., 2014. Poecilogonalos maga Teranishi, 1929, syn. n. and Taiwanogonalos claripennis Tsuneki, 1991, syn. n. are new synonyms of Taeniogonalos taihorina (Bischoff, 1914) and Taiwanogonalos alishana Tsuneki, 1991, syn. n. of Taeniogonalos alticola (Tsuneki, 1991). Revised keys to species of the genera Bareogonalos , Jezonogonalos , and Orthogonalys are included.

Prior to entering diapause, insects must prepare themselves physiologically to withstand the stresses of arresting their development for a lengthy period. While studies describing the biochemical and cellular milieu of the maintenance phase of diapause are accumulating, few studies have taken an "omics" approach to describing molecular events during the diapause preparatory phase. We used isobaric tags and mass spectrometry (iTRAQ) to quantitatively compare the expression profiles of proteins identified during the onset of diapause preparation phase in the heads of adult female cabbage beetles, Colaphellus bowringi . A total of 3,175 proteins were identified, 297 of which were differentially expressed between diapause-destined and non-diapause-destined female adults and could therefore be involved in diapause preparation in this species. Comparison of identified proteins with protein function databases shows that many of these differentially expressed proteins enhanced in diapause destined beetles are involved in energy production and conversion, carbohydrate metabolism and transport, and lipid metabolism. Further hand annotation of differentially abundant peptides nominates several associated with stress hardiness, including HSPs and antioxidants, as well as neural development. In contrast, non-diapause destined beetles show substantial increases in cuticle proteins, suggesting additional post-emergence growth. Using RNA interference to silence a fatty acid-binding protein (FABP) that was highly abundant in the head of diapause-destined females prevented the accumulation of lipids in the fat body, a common product of diapause preparation in this species and others. Surprisingly, RNAi against the FABP also affected the transcript abundance of several heat shock proteins. These results suggest that the identified differentially expressed proteins that play vital roles in lipid metabolism may also contribute somehow to enhanced hardiness to environmental stress that is characteristic of diapause.

Diapause (also known as dormancy) is a state of arrested development induced by photoperiod or temperature that allows insects to survive adverse environmental conditions. By regulating diapause induction, the circadian clock is involved in short-day-induced winter diapause but whether this is also the case in long-day (LD)-induced summer diapause remains unknown. The cabbage beetle Colaphellus bowringi could enter summer diapause under LD conditions. However, a non-photoperiodic-diapause (NPD) strain of this species, which was developed in our laboratory by artificial selection, could not enter diapause under LD photoperiod. Therefore, we identified circadian clock genes in this species and measured differences in their expression between a high diapause (HD) strain and the NPD strain to investigate the potential relationship between circadian clock genes and summer diapause induction in C. bowringi. We successfully cloned eight circadian clock genes and obtained intact ORFs of four; cryptochrome2, double-time, shaggy and vrille. Phylogenetic trees and sequence alignment analyses indicated that these circadian clock genes were conserved across insect taxa. The quantitative real-time PCR indicated that clock, cycle, period, timeless, cryptochrome2, and vrille were differentially expressed between HD and NPD strains reared under LD photoperiod during the diapause induction phase. These findings suggest the potential relationship between circadian clock genes and LD-regulated summer diapause induction in C. bowringi., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Diapause, also known as dormancy, is a state of arrested development that allows insects to survive unfavorable environmental conditions. Diapause-destined insects store large amounts of fat when preparing for diapause. However, the extent to which these accumulated fat reserves influence diapause remains unclear. To address this question, we investigated the function of fatty acid synthase (FAS), which plays a central role in lipid synthesis, in stress tolerance, the duration of diapause preparation, and whether insects enter diapause or not. In diapause-destined adult female cabbage beetles, Colaphellus bowringi, FAS2 was more highly expressed than FAS1 at the peak stage of diapause preparation. FAS2 knockdown suppressed lipid accumulation and subsequently affected stress tolerance genes expression and water content. However, silencing FAS2 had no significant effects on the duration of diapause preparation or the incidence of diapause. FAS2 transcription was suppressed by juvenile hormone (JH) and the JH receptor methoprene-tolerant (Met). These results suggest that the absence of JH-Met induces FAS2 expression, thereby promoting lipid storage in diapause-destined female beetles. These results demonstrate that fat reserves regulate stress tolerance genes expression and water content, but have no significant effect on the duration of diapause preparation or the incidence of diapause.

Four new species of the genus Gasteruption Latreille, 1796 (Hymenoptera: Evanioidea: Gasteruptiidae: Gasteruptiinae) are reported from NW China: three from Shaanxi province and one from Ningxia province. The new species (Gasteruption bicoloratum Tan & van Achterberg, sp. n., Gasteruption huangshii Tan & van Achterberg, sp. n., Gasteruption pannuceum Tan & van Achterberg, sp. n., and Gasteruption shengi Tan & van Achterberg, sp. n.) and three newly recorded species (Gasteruption sinepunctatum Zhao, van Achterberg & Xu, 2012, Gasteruption boreale (Thomson, 1883) and Gasteruption oshimense Watanabe, 1924) are keyed and fully illustrated. In total, seven species are known from Shaanxi province, which is approximately half of the expected number. The East Palaearctic specimens provisionally identified as Gasteruption tournieri Schletterer, 1885, by Zhao et al. (2012) are included under Gasteruption oshimense Watanabe, 1924.

Aim: To investigate the possible association between CFH gene polymorphisms -543G>A (rs1410996), A473A (rs2274700), -257C>T (rs3753394), IVS15 (rs1329428) and AMD risk., Methods: We searched the published literature in the Medline and Scopus from inception to May 2015. A meta-analysis was performed by the programs RevMan 5.1 and Stata 12.0, and the Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated in fixed or random effect model based on heterogeneity test among studies., Results: Nineteen studies with a total of 10,676 subjects were included in the present meta-analysis. A statistical significant association was observed between AMD risk and CFH -543G>A polymorphism with OR of 1.77 (95% CI, 1.47-2.12), 2.24 (95% CI, 1.71-2.94), 0.49 (95% CI, 0.38-0.62) and 0.25 (95% CI, 0.18-0.37) in additive, dominant, recessive and codominant models, respectively. Similar results were obtained in polymorphisms A473A, -257C>T, IVS15. Furthermore, stratified analysis for ethnicity showed a significantly strong association between -543G>A, A473A polymorphisms and AMD risk., Conclusion: The present meta-analysis suggested that CFH -543G>A, A473A, -257C>T, and IVS15 polymorphisms might be moderately associated with AMD risk. This conclusion warrants confirmation by further studies., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Carinopius gen. n. (type species: Carinopius albocoxalis Tan & van Achterberg, sp. n.) from China (Yunnan) and Vietnam is described and illustrated (Hymenoptera: Braconidae: Opiinae).