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ObjectiveThe impact of primary biliary cholangitis (PBC) on sleep disturbance is relevant to treatment decision-making processes. Studies on sleep disturbance in Chinese patients with PBC are still lacking.MethodsWe analyzed and compared the health-related quality of life (HRQoL) of 107 PBC patients by using the Pittsburgh Sleep Quality Index (PSQI) questionnaire, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire 9 (PHQ-9), Short Form (36) Health Survey Questionnaire (SF-36), Fatigue Visual Analog Scale (F-VAS). Patients’ biochemical markers were also collected for correlation analysis with HRQoL. Receiver operating characteristic (ROC) curves and area under the curve (AUCs) were used to determine the diagnostic performance of PSQI, GAD-7, and biochemical markers for assessing the impaired liver function (Child–Pugh B–C) of PBC diagnosis.ResultsSixty-two (57.9%) PBC patients suffered from poor sleep quality (PSQI >5). The global PSQI score was positively correlated with GAD-7 (r = 0.561, p

Soil quality is defined as the ability of soil to maintain the soil environment and the biosphere. Due to the limitation of salt and alkali stress, soil quality can be reduced, which in turn affects agricultural production. Biochar is widely used in saline–alkali land improvement because of its special pore structure and strong ion exchange ability, while Piriformospora indica is widely used in saline–alkali land improvement because it can symbiose with plants and improve plant stress resistance. However, the synergistic effect of combined biochar application and inoculation of P. indica on the quality of saline–alkali soil and plant development is uncertain. Hence, we investigated the combined influences of biochar and P. indica on the soil physicochemical characteristics, as well as the growth and chlorophyll florescence of sorghum–sudangrass hybrids (Sorghum bicolor × Sorghum sudane) in our study. The results indicated that after applying biochar and P. indica together, there was a considerable drop in soil pH, conductivity, Na+, and Cl− concentrations. Meanwhile, the soil organic matter (SOM), available phosphorus (AP), and alkaline hydrolyzable nitrogen (AN) increased by 151.81%, 50.84%, and 103.50%, respectively, when the Bamboo biochar was combined with 120 ml/pot of P. indica. Eventually, sorghum–sudangrass hybrid biomass, transpiration rate, and chlorophyll content increased by 111.69%, 204.98%, and 118.54%, respectively. According to our findings, using P. indica and biochar together can enhance soil quality and plant growth. The results also provide insights to enhance the quality of saline–alkali soils and the role of microorganisms in nutrient cycling.

Background: In some patients especially those AMA negative, the diagnosis may be a challenge requiring liver biopsy. This study determined whether autotaxin, a secreted lysophospholipase D encoded by the exonucleotide pyrophosphatase phosphodiesterase 2 gene, can be used as a serum biomarker for primary biliary cholangitis. Methods: Plasma samples were collected from 103 patients with PBC and 74 healthy controls. autotaxin levels were determined by Enzyme-linked immunosorbent assay, and its predictive value for diagnosing primary biliary cholangitis was analysed. The relationship between autotaxin and the clinical data was also evaluated. Results: Autotaxin levels in patients with primary biliary cholangitis were significantly higher than those in healthy control (median: 60.7 ng/ml vs. 32.6 ng/ml, P

PM2.5 exposure leads to a variety of respiratory diseases, including pulmonary fibrosis, metastatic lung cancer, etc. Exposure to PM2.5 results in the alteration of epigenetic modification. M6A RNA methylation is an essential epigenetic modification that regulates gene expression at the post-transcriptional level. Our previous study found that PM2.5 exposure up-regulated m6A RNA methylation and TGF-β expression level in the lung, but the mechanisms and pathways of PM2.5 regulation of m6A RNA methylation are still unclear. Moreover, a previous study reported that the TGF-β signal pathway could regulate m6A RNA methylation. Based on this evidence, we investigate the role of the TGF-β signaling pathway in PM2.5-induced m6A RNA methylation with the A549 cell line. Our results showed that PM2.5 could induce upregulation of m6A RNA methylation, accompanied by increased expression of TGF-β, Smad3, methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14). Furthermore, these alterations induced by PM2.5 exposure could be reversed by treatment with TGF-β inhibitor. Therefore, we speculated that the TGF-β signal pathway plays an indispensable role in regulating m6A RNA methylation after PM2.5 exposure. Our study demonstrates that PM2.5 exposure influences m6A RNA methylation by inducing the alteration of the TGF-β signal pathway, which could be an essential mechanism for lung-related diseases induced by PM2.5 exposure.

The development of effective methods for dopamine detection is critical. In this study, a homogeneous colorimetric strategy for the detection of dopamine based on a copper sulfide and Prussian blue/platinum (CuS@PB/Pt) composite was developed. A rose-like CuS@PB/Pt composite was synthesized for the first time, and it was discovered that when hydrogen peroxide was present, the 3,3′,5,5′-tetramethylbenzidine (TMB) changed from colorless into blue-oxidized TMB. The CuS@PB/Pt composite was characterized with a scanning electron microscope (SEM), an energy dispersive spectrometer (EDS), and an X-ray photoelectron spectrometer (XPS). Moreover, the catalytic activity of the CuS@PB/Pt composite was inhibited by the binding of dopamine to the composite. The color change of TMB can be evaluated by the UV spectrum and a portable smartphone detection device. The developed colorimetric sensor can be used to quantitatively analyze dopamine between 1 and 60 µM with a detection limit of 0.28 μM. Furthermore, the sensor showed good long-term stability and good performance in human serum samples. Compared with other reported methods, this strategy can be performed rapidly (16 min) and has the advantage of smartphone visual detection. The portable smartphone detection device is portable and user-friendly, providing convenient colorimetric analysis for serum. This colorimetric strategy also has considerable potential for the development of in vitro diagnosis methods in combination with other test strips.

A simple colorimetric method based on a novel oxidase-like magnetic composite material (composed of ferric oxide, amine-dendrimer and terminated manganese dioxide, Fe3O4/PAMAM/MnO2) was constructed for the detection of hydrogen sulfide (H2S) in tap water. The Fe3O4/PAMAM/MnO2 composite was prepared by in-situ reduction, which can oxidize 4,3,3,5, 5-tetramethylbenzidine (TMB) directly to form blue oxidized TMB (ox TMB) without the addition of other oxidants in 2 min. In the present of H2S, the corresponding activities of Fe3O4/PAMAM/MnO2 composite are greatly weakened under the optimal conditions. And the absorbance at 652 nm was linear to the concentration of H2S with the limit of detection of H2S was 0.89 μM. Selectivity experiment results show that the method has good selectivity, and the method has been successfully applied to the determination of H2S in environmental water samples.

Abstract Background A reliable and effective method is required to deliver agent that can aid the in vivo imaging of retinal vessels. The aim of the present study was to evaluate retro-orbital (RO) injection of fluorescein-labeled isothiocyanate dextran (FITC-dextran) as a method of demonstrating retinal neovascularization (NV) and avascular areas in oxygen-induced retinopathy (OIR) mice. Methods Different concentrations of FITC-dextran were used to compare the efficacy of this agent in perfusing the retinal vessels. Hematoxylin–eosin (HE) staining was used to evaluate the safety of RO injection. The vitreous blood vessels and extent of NV were assessed in P17 OIR mice using FITC-dextran and compared with the corresponding measurements obtained following isolectin B4 staining or the combination of both methods. Results The fluorescence of small vessels and neovascular tufts could be observed clearly following RO injection of 0.05 ml of 25 mg/ml or 50 mg/ml FITC-dextran. No visible damage to tissues adjacent to the injection site was discovered. Vitreous blood flow was gradually reduced from P0 to P5 and eventually disappeared in P17 OIR mice, as demonstrated by FITC-dextran perfusion. The retinal NV areas assessed by isolectin B4 were larger than those assessed by FITC-dextran, but the retinal avascular areas were smaller. The combination of both methods could conduce to distinguish non-functional blood vessels. Conclusions RO injection of FITC-dextran combined with isolectin B4 is an effective, optimal method for assessing the NV area and avascular area.

Energy storage systems are widely used in various fields such as renewable energy generation, hybrid electric vehicle, power grid, etc. However, the difference in characteristics among energy storage cells is one of the bottlenecks faced by large-scale application of energy storage systems, and the voltage imbalance among cells will gradually increase due to nonuniform characteristics. To solve this problem, this paper proposed a transformer-less voltage equalizer based on multi-stacked type converters for series-connected energy storage cells. Only two switches controlled by same driving signals are required and all cell voltages become uniform automatically without current sensor, voltage sensor and closed-loop control. Compared with the conventional single-switch voltage equalizer, the proposed equalizer not only inherits the current limit characteristic of conventional equalizer in discontinuous conduction mode operation but also obtains higher equalization speed and reduced current ripple. Operation principles and characteristics analysis of proposed equalizer are introduced, and the experimental verification are carried out to verify the effectiveness and superiority of proposed equalizer.

Abstract Glaucoma is well-known clinical eye conditions that damage the optic nerve due to abnormal pressure conditions in eye. Hesperidin is well-known glycoside widely present in the citrus fruits, and its aglycone form is known as hesperetin. Hesperidin is major flavone found in orange fruits. Hypotensive effect of hesperidin in acute and chronic glaucoma rats, glutamate level in vitreous humour and glutathione (GSH) level in aqueous humour were determined following 25, 50 and 100 mg/kg of hesperidin treatment. Acetazolamide (5 mg/kg) was used as positive control. Hesperidin treatment significantly reduced the increased intraocular pressure (IOP) level in dextrose induced ocular hypertension than saline treated rats. The effect of hesperidin was comparable to the positive control acetazolamide. Similarly, hesperidin treatment significantly reduced the IOP level in prednisolone acetate induced ocular hypertension than saline treated rats. In the aqueous humour, hesperidin treatment increased the glutathione level 125%, 184.4% and 231.2% at 25, 50 and 100 mg/kg of hesperidin respectively. In the vitreous humour, hesperidin treatment reduced the glutamate level 9.9%, 13.2% and 25.3% at 25, 50 and 100 mg/kg of hesperidin respectively. Histopathological analysis of normal saline treated rats showed morphological alteration in ciliary bodies. However, rats treated with hesperidin showed the reduced level of morphological alteration in ciliary bodies. Taking all these data together, it is suggested that the hesperidin supplementation was effective against glaucoma in experimental rats.

Extreme disasters may cause the power supply to the distribution system (DS) to be interrupted. The DS is forced to operate in island mode and forms an islanded microgrid (MG). In order to improve the post-disaster resilience of the DS and to provide longer power supply for as many loads as possible with limited generation resources, this paper proposes a multi-agent deep reinforcement learning (DRL) method which realizes a dual control on the source and load sides of the MG. The problem of resilience improvement is converted to a sequential decision making problem, where the objective is to maximize the cumulative MG utility value over the power outage duration. A multi-agent DRL model is proposed to solve the sequential decision making problem. A dual control policy including energy storage management and load shedding strategy is put forward to maximize the utility value of the MG. A reinforcement learning (RL) environment based on OpenAI and OpenDSS for islanded MG is constructed as a simulator, which has a general interface compatible with, and also can be published to, OpenAI Gym. Numerical simulations are performed for an MG equipped with wind turbines, diesel generators, and storage devices to validate the effectiveness of the proposed method. The influences of available generation resources and power outage duration on the control policy are discussed, which validates the strong adaptability of the proposed method in different conditions.

Purpose. To analyze the visual prognosis of macular buckling in patients with high myopia foveoschisis (FS) and to identify factors that predict the final visual outcome. Methods. We retrospectively included 155 eyes of 155 patients who underwent foveoschisis-related macular buckling. Best-corrected visual acuity (BCVA) and coexisting macular pathologies were assessed as a measure of surgical outcome, and multivariate linear regression was performed to identify factors affecting final visual prognosis. Results. The mean preoperative BCVA was 1.19 ± 0.55 logMAR (20/308), while the mean postoperative BCVA was 0.82 ± 0.51 logMAR (20/133) (P

Purpose: We performed single-cell RNA sequencing (scRNA-seq), an unbiased and high-throughput single cell technology, to determine phenotype and function of peripheral immune cells in patients with diabetic macular edema (DME).Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from DME patients and healthy controls (HC). The single-cell samples were loaded on the Chromium platform (10x Genomics) for sequencing. R package Seurat v3 was used for data normalizing, clustering, dimensionality reduction, differential expression analysis, and visualization.Results: We constructed a single-cell RNA atlas comprising 57,650 PBMCs (24,919 HC, 32,731 DME). We divided all immune cells into five major immune cell lineages, including monocytes (MC), T cells (TC), NK cells (NK), B cells (BC), and dendritic cells (DC). Our differential expression gene (DEG) analysis showed that MC was enriched of genes participating in the cytokine pathway and inflammation activation. We further subdivided MC into five subsets: resting CD14++ MC, proinflammatory CD14++ MC, intermediate MC, resting CD16++ MC and pro-inflammatory CD16++ MC. Remarkably, we revealed that the proinflammatory CD14++ monocytes predominated in promoting inflammation, mainly by increasingly production of inflammatory cytokines (TNF, IL1B, and NFKBIA) and chemokines (CCL3, CCL3L1, CCL4L2, CXCL2, and CXCL8). Gene Ontology (GO) and pathway analysis of the DEGs demonstrated that the proinflammatory CD14++ monocytes, especially in DME patients, upregulated inflammatory pathways including tumor necrosis factor-mediated signaling pathway, I-kappaB kinase/NF-kappaB signaling, and toll-like receptor signaling pathway.Conclusion: In this study, we construct the first immune landscape of DME patients with T2D and confirmed innate immune dysregulation in peripheral blood based on an unbiased scRNA-seq approach. And these results demonstrate potential target cell population for anti-inflammation treatments.

With the random discharging of industrial and agricultural wastewater, a large amount of cadmium (Cd) has accumulated in the soil, which seriously affects the growth of crops and people’s food safety. In this study, alfalfa was used as the material for studying the effects of the inoculation of Piriformospora indica (P. indica) on photosynthesis, osmoregulatory substances, and antioxidant enzymes of alfalfa seedlings at different Cd concentrations (0, 5, 10, 30, 50, and 100 mg/L) through hydroponic experiments. The results showed that with the increase in Cd concentration, the chlorophyll content, net photosynthetic rate (Pn), transpiration rate (Tr), and stomatal conductance (Gs) of alfalfa all decreased gradually, while the intercellular CO2 concentration (Ci) decreased at first and then increased. However, compared with non-inoculated control plants, the inoculation of P. indica improved the photosynthesis (41.97%) of alfalfa under Cd stress, increased the chlorophyll content (43.70%), and significantly increased the contents of proline (29.86%), soluble proteins (38.54%), and antioxidant enzyme activities. It was concluded that P. indica alleviates the negative effects of Cd on alfalfa plants to some extent. This is because P. indica can resist Cd stress and improve plant growth in cadmium-contaminated agricultural soil by alleviating membrane peroxidation damage, regulating osmotic regulatory substances, and enhancing enzyme activity to improve the antioxidant defense system. Thus, P. indica can be considered a biological fertilizer for improving plant growth and physiology in soils contaminated with cadmium.

A highly sensitive self-powered photoelectrochemical (spPEC) sensing platform was constructed for Hg2+ determination based on the g-C3N4-CdS-CuO co-sensitized photoelectrode and a visible light-induced redox cycle for signal amplification. Through successively coating the single-layer g-C3N4, CdS, and CuO onto the surface of an electrode, the modified electrode exhibited significantly enhanced PEC activity. The microstructure of the material was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). However, the boost in photocurrent could be noticeably suppressed due to the consumption of hole-scavenging agents (reduced glutathione) by the added Hg2+. Under optimal conditions, we discovered that the photocurrent was linearly related to the Hg2+ concentration in the range of 5 pM–100 nM. The detection limit for Hg2+ was 0.84 pM. Moreover, the spPEC sensor demonstrated good performance for the detection of mercury ions in human urine and artificial saliva.

Introduction Diabetic retinopathy (DR) is the main cause of adult visual impairment worldwide. Severe non-proliferative DR (sNPDR) is an important clinical intervention stage. Currently, panretinal photocoagulation (PRP) is the standard treatment for sNPDR. However, PRP alone cannot completely prevent NPDR progression. One explanation might be that PRP does not remove the detrimental vitreous that plays an important role in DR progression. Microinvasive pars plana vitrectomy (PPV) was shown to be a safe and effective method to treat late-stage proliferative DR (PDR) by completely removing the pathological vitreous. However, whether PPV is effective in controlling sNPDR remains unknown. In this trial, we aim to compare the effectiveness of microinvasive PPV with that of PRP for sNPDR progression control.Methods and analysis This single centre, parallel group, randomised controlled trial aims to evaluate the clinical efficacy of microinvasive PPV in preventing the progression of sNPDR compared with PRP. A total of 272 adults diagnosed with sNPDR will be randomised 1:1 to the microinvasive PPV and PRP groups. The primary outcome is the disease progression rate, calculated as the rate of sNPDR progressed to PDR from baseline to 12 months after treatment. The secondary outcomes include the change in best-corrected visual acuity, re-treatment rate, diabetic macular oedema occurrence, change in central retinal thickness, change in the visual field, cataract occurrence and change in the quality of life.Ethics and dissemination The Ethics Committee of Zhongshan Ophthalmic Center approved this study (2019KYPJ108). The results will be presented at scientific meetings and submitted for publication to peer-reviewed journals.Trial registration number NCT04103671.

BackgroundBladder cancer (BCa) represents one of the most common malignant cancers with high incidence and mortality rates globally. Dysregulation of gene expression has been shown to play critical roles in cancer progression. RAC3 is up-regulated to play an oncogenic role in several cancers, however, the underlying mechanism of RAC3 in BCa is yet to be elucidated. Therefore, this study aimed to investigate the function and mechanism of RAC3 in BCa.MethodsBioinformatics analysis was employed to demonstrate the expression of RAC3 and PYCR1 in BCa tissues, as well as, its correlation with the overall survival rate of BCa patients. RT-qPCR was performed to detect and quantify the mRNA levels of RAC3 and PYCR1 in BCa cells and immortalized human bladder epithelial cells. MTT, colony formation and Transwell assays were employed to determine cell proliferation, migration, and invasion. Western blotting was performed to detect and quantity proteins expressed.ResultsBioinformatics analysis showed that RAC3 was up-regulated in BCa tissues when compared to normal tissues. Patients with up-regulated RAC3 expression had lower overall survival than patients with down-regulated RAC3 expression. The mRNA level of RAC3 was higher in BCa cells than in immortalized human bladder epithelial cell. RAC3 promoted cell proliferation, migration, and invasion by activating Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) signaling. Notably, RAC3 up-regulated PYCR1, which is positively correlated with RAC3, and thus played an oncogenic role in BCa cells. Moreover, we demonstrated that RAC3 overexpression activated JAK/STAT signaling via PYCR1 axis.ConclusionRAC3 promoted cell proliferation, migration, and invasion. This is likely due to its role in activating JAK/STAT signaling, which was mediated by PYCR1. This study provides a novel biomarker and target for diagnostic or therapeutic intervention for BCa.

Although China is a global trade power, it has low value-added trade, which lies at the bottom of the global value chain. Therefore, there is an urgent need to change the unfavorable position of the international division of labor in China. The global innovation chain is a new development of innovation through which China can implement open innovation and utilize the world's advanced knowledge, technology, information, and other resources to enhance its innovation capabilities, promote industrial upgrading, and improve the status of its global value chains. This paper takes Huawei as an example of international cooperation and innovation, aspects that have allowed the company to rapidly improve its position and prestige in the industry. The case study of Huawei suggests that China should introduce talent, increase investment abroad, attract foreign investment, expand intellectual property trade, develop outsourcing and international strategic research and development alliances, build a global innovation chain, and promote industrial upgrading to elevate the status of its international division of labor. Keywords: Global innovation chain, Global value chain, Open innovation, International innovation cooperation

Human induced pluripotent stem cell (iPSC) lines were generated from fibroblasts of a patient affected with an autosomal dominant retinal dystrophy carrying the mutation c.782A>C, p.Glu261Ala in ITM2B and from an unaffected brother. Three different iPSC lines were generated and characterized from primary dermal fibroblasts of the affected subject and two from the unaffected brother. All iPSC lines expressed the pluripotency markers, were able to differentiate into the three germ layers and presented normal karyotypes. This cellular model will provide a powerful tool to study this retinal dystrophy and better understand the role of ITM2B.

Abstract Background Management of neuropathic pain is a real clinical challenge. Despite intense investigation, the mechanisms of neuropathic pain remain substantially unidentified. Matrix metalloproteinase (MMP)-9 and MMP-2 have been reported to contribute to the development and maintenance of neuropathic pain. Therefore, inhibition of MMP-9/2 may provide a novel therapeutic approach for the treatment of neuropathic pain. In this study, we aim to investigate the effect of procyanidins (PC), clinically used health product, on MMP-9/2 in neuropathic pain. Methods The nociception was assessed by measuring the incidence of foot withdrawal in response to mechanical indentation in mice. Cell signaling was assayed using gelatin zymography, western blotting, and immunohistochemistry. The BV2 cells were cultured to investigate the effects of PC on microglia. Results Both in vitro and in vivo administration of PC significantly suppresses the activity of MMP-9/2. Oral administration of PC relieves neuropathic pain behaviors induced by chronic constriction sciatic nerve injury (CCI) in mice. Additionally, PC blocks the maturation of interleukin-1β, which is a critical substrate of MMPs, and markedly suppresses CCI-induced MAPK phosphorylation and neuronal and microglia activation, including the reduced phosphorylation of protein kinase C γ and NMDAR1. Furthermore, PC decreases the phosphorylation of p38 mitogen-activated protein kinase and inhibits the translocation of nuclear factor-κB (NF-κB) in microglia. Conclusions PC is an effective and safe approach to alleviate neuropathic pain via a powerful inhibition on the activation of MMP-9/2.

Abstract Background Subfoveal choroidal thickness (SFCT) in highly myopic eyes was found to be correlated with increasing age, refractive error (spherical equivalent), and axial length. Which factor is the most significant predictor of SFCT remains controversial. Methods A hospital-based cohort of highly myopic eyes (with spherical equivalent equal to or over 6.00 diopter) were retrospectively screened. Data from only right eye in those bilateral high myopia, and unilateral high myopia in any eye, were used for analysis. Correlations among the four biometric factors were analyzed. Linear correlation was performed to analyze the predictors of SFCT. Results A cohort of 312 eyes from 312 adults (98 men) was enrolled. Statistical analysis showed that axial length (R = − 0.592), spherical equivalent (R = − 0.471), and age (R = − 0.296) were significantly correlated with SFCT (P

To satisfy the grid-connected voltage level, both photovoltaic modules and energy storage modules are connected in series. However, the multiple photovoltaic modules often fall into local maximum power point under partial shading conditions during practical operation, and the multiple energy storage modules may suffer from a reduction in the effective capacity caused by characteristic differences among modules. To solve this problem, a novel cascaded modular photovoltaic-energy storage system is proposed in this paper. In the proposed topology, the energy storage modules achieve maximum power point tracking of the corresponding distributed photovoltaic module, and the proposed energy optimization strategy based on particle swarm optimization can ensure the efficient constant active power transmission from a photovoltaic energy storage (PV/ES) system to the grid in a certain time period under capacity constraints. Compared with conventional photovoltaic systems, the proposed scheme can avoid hot spots or the hot strings phenomena for PV modules and the large current and voltage stresses for DC/DC converters. Furthermore, the proposed energy optimization strategy for the coordination of all ES modules can realize the independent MPPT of each PV module and the constant active power between the PV/ES system and the grid under inconsistency of the light intensity under partial shading conditions. A hardware-in-loop photovoltaic-energy platform is established to verify the feasibility and effectiveness of the proposed topology and control strategy, and the proposed system achieves efficiency of about 97% under partial shading conditions, thus providing an effective and practical solution for power generation system.

Abstract Background Transscleral tunnel incisions are commonly made to avoid postoperative leakage in small gauge sutureless vitrectomy. We present an unreported intraoperative complication, tunnel incision related arterial hemorrhage from sclerotomy, in 23-gauge (23G) vitrectomy. Case presentation Two cases of intraocular arterial hemorrhage from superonasal sclerotomy were observed at the beginning of vitrectomy. The bleeding filled the vitreous cavity quickly and gushed out from the incision port after the involved supronasal cannula was removed. The active bleeding seemed not to stop spontaneously. We controlled the active bleeding by relocating the involved cannula, elevating the intraocular pressure and compressing the sclera wound. Post-operative intraocular hemorrhage from the sclerotomy was not found in any of the two cases. Conclusions We suggest that the bleeding was from injured ciliary artery when the incision crossed 3 or 9 o’clock accidently. Surgeons might avoid this complication by locating the superior incisions away from the horizontal axis, and should be aware the proper management.

Tumor metastasis is the major cause of mortality of cancer patients, being responsible for ∼90% of all cancer deaths. One of the key steps during tumor metastasis is tumor cell migration which requires actin cytoskeletal reorganization. Among the critical actin cytoskeletal protrusion structures are antenna‐like filopodia. Fascin protein is the main actin‐bundling protein in filopodia. Here we report the development of fascin‐specific small‐molecules that inhibit the interaction between fascin and actin. These inhibitors block the in vitro actin‐binding and actin‐bundling activities of fascin, tumor cell migration and tumor metastasis in mouse models. Mechanistically, these inhibitors likely occupy one of the actin‐binding sites, reduce the binding of actin filaments, and thus lead to the inhibition of the bundling activity of fascin. At the cellular level, these inhibitors impair actin cytoskeletal reorganization. Our data indicate that target‐specific anti‐fascin agents will have great potential for treating metastatic tumors.

According to the framework of emotion regulation (ER), both explicit and implicit forms are essential to our well-being. It is the interaction between these two processes that ensures adaptive emotional responses. Although many studies have focused on explicit ER deficits in anxiety, there is still a lack of awareness about the implicit form and its role in anxiety. To address this issue, we explored the time course of implicit ER processes in individuals with high and low trait anxiety (LTA). To do this, we employed the newly developed Priming-Identify (PI) paradigm, which includes a word-matching task (externally-generated implicit goals) and a facial expression identification task (emotion processing). We aimed to modulate the implicit ER goals of individuals through the application of different priming conditions (ER-related and -unrelated words). In addition to their behavioral effects, we recorded the influence of these priming conditions through event-related potentials (ERPs) during the facial expression identification task. Three ERP components were chosen as indexes of three stages of implicit ER processing: N170, early posterior negativity (EPN) and late positive potential (LPP). In individuals with LTA, the early N170 and the middle EPN were enlarged under the ER-related priming condition, while the LPP was not influenced. However, in individuals with high trait anxiety (HTA), we observed an absence of any significant differences between the ER-related and -unrelated priming conditions across all three ERP components. Furthermore, enlargements of N170 and EPN amplitudes were significantly correlated with a decrease in negative emotion experience scores. Our results suggest that HTA individuals experience implicit ER deficits during the early and middle stages of ER.

This study aims to evaluate the efficacy of ketorolac with local anesthesia compared to local anesthesia alone for perioperative pain control in day care retinal detachment surgery. The randomized controlled trial included 59 eyes of 59 participants for retinal detachment surgery who were randomly assigned (1 : 1) into the ketorolac (K) group and control (C) group. All participants underwent conventional local anesthesia while patients in the K group received an extra administration of preoperative ketorolac. Participants in the K group had a statistically significantly lower intraoperative NRS score (median 1.0 versus 3.0, P=0.003), lower postoperative NRS score (median 0 versus 1.0, P=0.035), fewer proportion of rescue analgesic requirement (10% versus 34.5%, P=0.023), and lower incidence of postoperative nausea and vomiting (13.3% versus 41.4%, P=0.015) compared to the C group. Intraocular pressure (IOP) changes (△IOP) were significantly reduced in the K group (median 1.9 versus 3.0, P=0.038) compared to the C group 24 hours postoperatively. In conclusion, the combination of local anesthesia with ketorolac provides better pain control in retinal detachment surgery compared to local anesthesia alone. The beneficial effect of ketorolac with local anesthesia may contribute to a wider-spread adoption of day care retinal detachment surgery. This trial is registered with ClinicalTrials.gov NCT02729285.

Recent reform of medical education highlights the growing concerns about the capability of the current educational model to equip medical school students with essential skills for future career development. In the field of ophthalmology, although many attempts have been made to address the problem of the decreasing teaching time and the increasing load of course content, a growing body of literature indicates the need to reform the current ophthalmology teaching strategies. Flipped classroom is a new pedagogical model in which students develop a basic understanding of the course materials before class, and use in-class time for learner-centered activities, such as group discussion and presentation. However, few studies have evaluated the effectiveness of the flipped classroom in ophthalmology education. This study, for the first time, assesses the use of flipped classroom in ophthalmology, specifically glaucoma and ocular trauma clerkship teaching. A total number of 44 international medical school students from diverse background were enrolled in this study, and randomly divided into two groups. One group took the flipped glaucoma classroom and lecture-based ocular trauma classroom, while the other group took the flipped ocular trauma classroom and lecture-based glaucoma classroom. In the traditional lecture-based classroom, students attended the didactic lecture and did the homework after class. In the flipped classroom, students were asked to watch the prerecorded lectures before the class, and use the class time for homework discussion. Both the teachers and students were asked to complete feedback questionnaires after the classroom. We found that the two groups did not show differences in the final exam scores. However, the flipped classroom helped students to develop skills in problem solving, creative thinking and team working. Also, compared to the lecture-based classroom, both teachers and students were more satisfied with the flipped classroom. Interestingly, students had a more positive attitude towards the flipped ocular trauma classroom than the flipped glaucoma classroom regarding the teaching process, the course materials, and the value of the classroom. Therefore, the flipped classroom model in ophthalmology teaching showed promise as an effective approach to promote active learning.

Human induced pluripotent stem cells (iPSCs) provide a valuable model for regenerative medicine and human disease research. To date, however, the reprogramming efficiency of human adult cells is still low. Recent studies have revealed that cell cycle is a key parameter driving epigenetic reprogramming to pluripotency. As is well known, retroviruses such as the Moloney murine leukemia virus (MoMLV) require cell division to integrate into the host genome and replicate, whereas the target primary cells for reprogramming are a mixture of several cell types with different cell cycle rhythms. Whether cell cycle synchronization has potential effect on retrovirus induced reprogramming has not been detailed. In this study, utilizing transient serum starvation induced synchronization, we demonstrated that starvation generated a reversible cell cycle arrest and synchronously progressed through G2/M phase after release, substantially improving retroviral infection efficiency. Interestingly, synchronized human dermal fibroblasts (HDF) and adipose stem cells (ASC) exhibited more homogenous epithelial morphology than normal FBS control after infection, and the expression of epithelial markers such as E-cadherin and Epcam were strongly activated. Futhermore, synchronization treatment ultimately improved Nanog positive clones, achieved a 15-20 fold increase. These results suggested that cell cycle synchronization promotes the mesenchymal to epithelial transition (MET) and facilitates retrovirus mediated reprogramming. Our study, utilization of serum starvation rather than additional chemicals, provide a new insight into cell cycle regulation and induced reprogramming of human cells.

Objective: The present study aimed to investigate the intermediary role of distress tolerance in Mindfulness-Based Intervention (MBI) with respect to self-perceived stress reduction. Method: One hundred and twenty-nine adults with a high level of emotional distress were randomized into MBI groups or a waiting-list group. Levels of mindfulness skills, self-perceived stress, and distress tolerance (tolerance, appraisal, absorption, and regulation) were measured four times: pre-test, week 3, week 6, and post-test. Results: The developmental trajectories modeled by the univariate latent growth curve showed that the factor intervention significantly predicted the slope of observing, non-reactivity, overall mindfulness, and distress appraisal during first six weeks. Bivariate latent growth curve models demonstrated a significant association between increases in the growth rate of distress appraisal and non-reactivity in participants receiving mindfulness training. Such an association was not observed among those who did not receive an MBI. Longitudinal mediation analyses further revealed that the effect of MBI on non-reactivity and self-perceived stress at week 6 was fully mediated by distress appraisal at week 3, respectively. Conclusions: Our results indicate that distress appraisal plays an important role during the earlier stage of MBI, which might contribute to a more effective and efficient intervention program in the future. [ABSTRACT FROM AUTHOR]