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AIM:To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE+/- mice (AChE knockout mice) of various ages.METHODS:Cultured ARPE-19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 μmol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE+/- mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer.RESULTS:Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE+/- mice retina were thinner than those in wild-type mice (PP+/- mice developed more slowly than wild-type mice (PP>0.05).CONCLUSION:In vivo, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina.

AIM: To evaluate the therapeutic effect of netrin-4 on the early acute phase of inflammation in the alkali-burned eye. METHODS: Eye drops containing netrin-4 or phosphate buffered saline (PBS) were administered to a alkali-burn-induced corneal acute inflammatory model four times daily. The clinical evaluations, including fluorescein staining and inflammatory index, were performed on day 1, 4 and 7 using slit lamp microscopy. Global specimens were collected on day 7 and processed for immunofluorescent staining. The levels of inflammatory mediators in the corneas were determined by real-time polymerase chain reaction (PCR). RESULTS: Exogenous netrin-4 administered on rat ocular surfaces showed more improvements in decreasing fluorescein staining on day 4 and 7, and resolved alkali burn-induced corneal inflammation index on day 7 (P

AIM: To observe the effect of phacoemulsification combined goniosynechialysis in treating absolute glaucoma after trabeculectomy.METHODS: Phacoemulsification combined goniosynechialysis was performed on 16 patients(16 eyes)with absolute glaucoma after trabeculectomy, and they were followed up for 6～12mo, The postoperative intraocular pressure(IOP)and anterior chamber depth, preoperative and postoperative medication types(quantity), preoperative and postoperative 1 month's status of anxiety and depression, symptoms of ocular surface were observed.RESULTS: The IOP decreased significantly after phacoemulsification combined goniosynechialysis. The mean IOP was 35.00±15.43mmHg preoperatively, and it was 12.00±6.69mmHg, 15.00±4.26mmHg and 15.3±5.2mmHg on 1d, 6 and 12mo after the surgery. The statistic difference was found between preoperative and postoperative(t=6.22, Pt=6.65, PCONCLUSION: Phacoemulsification combined goniosynechialysis in treating absolute glaucoma after trabeculectomy is a safe and effective surgical option.

Some published evidence has revealed that the dendritic cells can interact with pathogens that exist in the inner foreskin. This information provides a new vision that pathogens could play a role through the redundant prepuce; numerous studies have failed to find pathogens in prostates of patients who had chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, no studies have reported an association between foreskin length and CP/CPPS. Hence, we conducted a retrospective case-control study of clinical data from 322 CP/CPPS patients (case group) and 341 nonCP/CPPS patients (control group). Demographic characteristics, lifestyle factors, and foreskin lengths were collected and analyzed. Multivariate logistic regression was adopted to calculate the odds of foreskin length for CP/CPPS. According to the multivariate logistic regression results, when the foreskin length covered up more than half of the glans penis, the odds for CP/CPPS were higher with an increased foreskin (odds ratio (OR): 1.66, 95% confidence interval (CI): 1.04-2.66). In comparison, when the glans penis was completely covered by the foreskin, the OR value increased to 1.86 (95% CI, 1.2-2.88). The study results showed an association between foreskin length and the odds of CP/CPPS. When the foreskin length covered up more than half of the glans penis, there were greater odds for CP/CPPS. This possible mechanism might result from interaction between pathogens and DCs in the inner foreskin, consequently activating T-cells to mediate allergic inflammation in the prostate and producing the autoimmunizations causing CP/CPPS.

Background and objective Cisplatin-resistance in Lung cancer cells is widespread in the clinical treatment, seriously affecting the effects of the treatment of lung cancer. Therefore, the research of mechanisms of cisplain-resistance has significant meaning for developing new chemotherapeutic drug and solving the cisplain-resistance in clinic treatment. IKBKB is one of the most important catalytic subunits of IKK complexes. It plays an important regulatory role in activation of NF-κB. The aim of this study is to investigate the differential expression of IKBKB gene in human lung adenocarcinoma cells line A549 and the cisplatin-resistant variant A549/DDP and the mechanisms of cisplain-resistance induced by IKBKB gene. Methods MTT assay was employed to determine the sensitivity of A549 and A549/DDP cells line to cisplatin and the effect of IKBKB gene on A549 cell lines’ sensitivity to cisplatin. The mRNA level of IKBKB was determined by real-time PCR. Dual luciferase reporter gene experiment was employed to determine the activity of the NF-κB. Apoptosis rate of lung adenocarcinoma cells was determined by flow cytometry. Results Apoptosis rate and IC50 were significantly different in A549 and A549/DDP cells, the expression of mRNA level of IKBKB gene in A549/DDP was significantly higher than that in A549. Compared with control group, IKBKB gene was able to reduce the cisplain sensitivity of A549 cells. After A549 was transfected with pcDNA3.1/IKBKB plasmid, mRNA level of IKBKB was significantly increased, the sensitivity of cisplain was decreased, the IC50 was increased 2.85 fold, the apoptosis rate was decreased 59%, the activity of NF-κB has been greatly increased. Conclusion IKBKB inhibits cisplatin-induced apoptosis via the activation of NF-κB pathway. It will be helpful in the development of new anticancer drug and solving the challenge of cisplatin-resistance.

AIM: To investigate the efficacy and safety of Honghua preserved amniotic membrane (AM) for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery.METHODS: Totally 36 rabbits (36 eyes) were randomly divided into 3 groups:the experimental group (ocular trabeculectomy in combination with Honghua preserved AM transplantation), the control group (ocular trabeculectomy surgery in combination with AM implantation), and the blank group (single trabeculectomy). Clinical observations [including intraocular pressure (IOP), filtering blebs and complications], Masson-Trichrome staining, real-time quantitative reverse transcription-polymerase chain reaction (real-time PCR), Western blot were performed on different time points (D1, D7, D14, D21 and D56) after the surgery.RESULTS: After operated for 14d, there were statistically significant differences in the filtering blebs compared to the situation before operation (P<0.05), whereas no statistically difference on that among three groups (P>0.05). After 21d, the IOP of experimental group was lowest (P<0.05). There was significant difference between control group and blank group (P<0.05). On postoperative D14, the mean number of fibroblasts in the experimental group was significantly lower (40.6±10.2) compared to those in the control group (54.4±10.8) and blank group (68.2±11.6) (P<0.05, respectively). The mean numbers of the macrophage in the experimental and control groups were respcitively significantly lower versus the blank group (P<0.05, P<0.05, respectively). Compared to that in blank group, the level of transforming growth factor-β (TGF-β1) expression in sclera and conjunctival areas was reduced in the experimental and control groups on protein and mRNA level (PP>0.05).CONCLUSION:The trabeculectory surgery with Honghua preserved AM can control IOP, sustain the functional filtration bleb, inhibit the proliferation of fibroblasts and open the filtrating pathway on the rabbit glaucoma models.

This article is concerned with the bifurcation of limit cycles of a class of cubic reversible system having a center at the origin. We prove that this system has at least four limit cycles produced by the period annulus around the center under cubic perturbations

In this paper, the effects of the deformation temperature, the deformation reduction and the deformation rate on the microstructural formation, ferritic and martensitic phase transformation, stress–strain behaviors and micro-hardness in low-carbon ferritic stainless steel were investigated. The increase in deformation temperature promotes the formation of the fine equiaxed dynamic strain-induced transformation ferrite and suppresses the martensitic transformation. The higher deformation temperature results in a lower starting temperature for martensitic transformation. The increase in deformation can effectively promote the transformation of DSIT ferrite, and decrease the martensitic transformation rate, which is caused by the work hardening effect on the metastable austenite. The increase in the deformation rate leads to an increase in the ferrite fraction, because a high density of dislocation remains that can provide sufficient nucleation sites for ferrite transformation. The slow deformation rate results in dynamic recovery according to the stress–strain curve.

AIM: To observe the clinical effect of Buddleja officinalis and Xueshuangtong capsule treating the mild and moderate simple diabetic retinopathy(sDR). METHODS: Based on the strict control of blood glucose and blood pressure, eighty patients(160 eyes)with mild and moderate sDR were randomized into two groups equally: Buddleja officinalis(15g,tid)and Xueshuangtong capsule administered to group A and only Xueshuangtong capsule administered to group B. They are taken before meals half an hour. The vision, funduscopy, FFA, fundus photography and traditional chinese medcine symptoms(TCMS)were evalutated before and after treatment in 7d,42 d respectively.RESULTS: There were no significant difference between two groups in terms of patients' gender, age, DM course, visual acuity, course of disease and TCM syndrome.(χ 2 sex=0.472, P>0.05; tage=1.742,tDM condition=0.716,tvision=0.662,tDR degree=1.276,tDR condition=0.562,t TCMS=0.616,P >0.05); Follow up for 42d on average after treatment the effective rate of fundus lesions of group A was 56%and the total effective rate was 82%,while the effective rate of group B was 32% and the total effective rate was 66%. The result showed that the curative effect of group A was better than that of group B. There were statistically significant difference for the effective rate between the two groups(χ2=8.025, Pχ 2=5.980,PCONCLUSION: Buddleja officinalis and Xueshuangtong capsule can improve the vision of patients with the mild and moderate sDR patients, the fundus lesions and the TCMS.

Obstructive sleep apnea (OSA) has been associated with changes in brain structure and regional function in certain brain areas. However, the functional features of network organization in the whole brain remain largely uncertain. The purpose of this study was to identify the OSA-related spatial centrality distribution of the whole brain functional network and to investigate the potential altered intrinsic functional hubs.Forty male patients with newly confirmed severe OSA on polysomnography, and well-matched good sleepers, participated in this study. All participants underwent a resting-state functional MRI scan and clinical and cognitive evaluation. Voxel-wise degree centrality (DC) was measured across the whole brain, and group difference in DC was compared. The relationship between the abnormal DC value and clinical variables was assessed using a linear correlation analysis.Remarkably similar spatial distributions of the functional hubs (high DC) were found in both groups. However, OSA patients exhibited a pattern of significantly reduced regional DC in the left middle occipital gyrus, posterior cingulate cortex, left superior frontal gyrus, and bilateral inferior parietal lobule, and DC was increased in the right orbital frontal cortex, bilateral cerebellum posterior lobes, and bilateral lentiform nucleus, including the putamen, extending to the hippocampus, and the inferior temporal gyrus, which overlapped with the functional hubs. Furthermore, a linear correlation analysis revealed that the DC value in the posterior cingulate cortex and left superior frontal gyrus were positively correlated with Montreal cognitive assessment scores, The DC value in the left middle occipital gyrus and bilateral inferior parietal lobule were negatively correlated with apnea-hypopnea index and arousal index in OSA patients.Our findings suggest that OSA patients exhibited specific abnormal intrinsic functional hubs including relatively reduced and increased DC. This expands our understanding of the functional characteristics of OSA, which may provide new insights into understanding the dysfunction and pathophysiology of OSA patients.

Netrins are secreted molecules involved in axon guidance and angiogenesis. However, the role of netrins in the vasculature remains unclear. Netrin-4 and netrin-1 have been found to be either pro- or antiangiogenic factors. Previously, we found that netrin-1 acts as an anti-angiogenic factor in rats by inhibiting alkali burn-induced corneal neovascularization. Here, we further investigate the effects of netrin-4, another member of the same netrin family, on neovascularization in vitro and in vivo. We found that netrin-4 functions similarly as netrin-1 in angiogenesis. In vitro angiogenesis assay shows that netrin-4 affected human umbilical vein endothelial cell (HUVEC) tube formation, viability and proliferation, apoptosis, migration, and invasion in a dose-dependent manner. Netrin-4 was topically applied in vivo to alkali-burned rat corneas on day 0 (immediately after injury) and/or day 10 post-injury. Netrin-4 subsequently suppressed and reversed corneal neovascularization. Netrin-4 inhibited corneal epithelial and stromal cell apoptosis, inhibited vascular endothelial growth factor (VEGF), but promoted pigment epithelium-derived factor (PEDF) expression, decreased NK-KB p65 expression, and inhibits neutrophil and macrophage infiltration. These results indicate that netrin-4 shed new light on its potential roles in treatmenting for angiogenic diseases that affect the ocular surface, as well as other tissues.

The mechanical properties of the high-strength low-alloy pipeline steels were mainly controlled by the subsequent phase transformations after rolling. The influence of hot uniaxial compression on the phase transformation of acicular ferrite was explored by viewing of the deformation degree, the deformation temperature, and the strain rate. The results show that the increase of deformation amounts raises the transformation starting and finishing temperature during the subsequent cooling and also promotes the polygonal ferrite transformation, which leads to the decrease of Vickers hardness accordingly. With the increasing of the deformation temperature, the achieved microstructure becomes coarsened and thus decreases the hardness. As the strain rate increases, the microstructure is refined and thus the hardness increases gradually; increasing the strain rate appropriately is beneficial to the refinement of the microstructure.

Liquid-phase electron microscopy (LP-EM) imaging has revolutionized our understanding of nanosynthesis and assembly. However, the current closed geometry limits its application for open systems. The ubiquitous physical process of the coffee-ring phenomenon that underpins materials and engineering science remains elusive at the nanoscale due to the lack of experimental tools. We introduce a quartz nanopipette liquid cell with a tunable dimension that requires only standard microscopes. Depending on the imaging condition, the open geometry of the nanopipette allows the imaging of evaporation-induced pattern formation, but it can also function as an ordinary closed-geometry liquid cell where evaporation is negligible despite the nano opening. The nano coffee-ring phenomenon was observed by tracking individual nanoparticles in an evaporating nanodroplet created from a thin liquid film by interfacial instability. Nanoflows drive the assembly and disruption of a ring pattern with the absence of particle-particle correlations. With surface effects, nanoflows override thermal fluctuations at tens of nanometers, in which nanoparticles displayed a "drunken man trajectory" and performed work at a value much smaller than kBT. [ABSTRACT FROM AUTHOR]

Expensive and unsustainable fishmeal is increasingly being replaced with cheaper lipids and carbohydrates as sources of energy in aquaculture. Although it is known that the excess of lipids and carbohydrates has negative effects on nutrient utilization, growth, metabolic homeostasis, and health of fish, our current understanding of mechanisms behind these effects is limited. To improve the understanding of diet-induced metabolic disorders (both in fish and other vertebrates), we conducted an eight-week high-fat--high-carbohydrate diet feeding trial on blunt snout bream (Megalobrama amblycephala), and studied gene expression changes (transcriptome and qPCR) in the liver. Disproportionately large numbers of differentially expressed genes were associated with mitochondrial metabolism, neurodegenerative diseases (Alzheimer's, Huntington's, and Parkinson's), and functional categories indicative of liver dysfunction. A high-fat--high-carbohydrate diet may have caused mitochondrial dysfunction, and possibly downregulated the mitochondrial biogenesis in the liver. While the relationship between diet and neurodegenerative disorders is well-established in mammals, this is the first report of this connection in fish. We propose that fishes should be further explored as a potentially promising model to study the mechanisms of diet-associated neurodegenerative disorders in humans. Key words: animal model, liver dysfunction, Megalobrama amblycephala, mitochondrial metabolism, neurodegenerative disorders. Les farines de poisson, coûteuses et non-renouvelables, sont de plus en plus remplacees par des lipides et des glucides moins coûteux en tant que source d'energie en aquaculture. Bien qu'il soit connu que l'exces de lipides et de glucides puisse avoir des effets negatifs sur l'utilisation des nutriments, l'homeostasie metabolique et la sante des poissons, notre comprehension des mecanismes expliquant ces effets est limitee. Pour ameliorer la comprehension des desordres metaboliques induits par la diete (tant chez les poissons que d'autres vertebres), les auteurs ont realise une experience alimentaire de huit semaines avec une diete elevee en lipides et en glucides chez le Megalobrama amblycephala, et ils ont etudie les changements d'expression genique (transcriptome et qPCR) chez le foie. Un nombre disproportionne de genes differentiellement exprimes etaient associes avec le metabolisme mitochondrial, les maladies neurodegeneratives (Alzheimer, Huntington et Parkinson) et des categories fonctionnelles indicatrices de dysfonctionnement du foie. La diete elevee en gras et en glucides pourrait avoir cause une dysfonction mitochondriale, et possiblement mene a une baisse de la biogenese mitochondriale chez le foie. Tandis que la relation entre la diete et les desordres neurodegeneratifs est bien etablie chez les mammiferes, il s'agit de la premiere fois qu'un tel lien est fait chez un poisson. Les auteurs proposent que les poissons soient davantage explores a titre de modele pour l'etude des mecanismes liant la diete et les desordres neurodegeneratifs chez l'humain. [Traduit par la Redaction] Mots-cles : modele animal, dysfonction du foie, Megalobrama amblycephala, metabolisme mitochondrial, desordres neurodegeneratifs., Introduction The widespread trend of replacing expensive and unsustainable fishmeal (FAO 2002) in aquaculture feed production with cheaper and more sustainable energy and protein sources has been accompanied by a [...]