The lack of homology domain and leucine rich repeat protein phosphatase 2 ameliorates visual impairment in rats with diabetic retinopathy through regulation of the AKT-GSK-3ß-Nrf2 signal cascade.

Pleckstrin homology domain and leucine rich repeat protein phosphatase 2 (PHLPP2) is an emerging player in diverse disorders. Our previous findings have documented that reducing PHLPP2 levels in cultured retinal ganglion cells protects against cellular damage caused by high glucose, indicating a possible link between PHLPP2 and diabetic retinopathy (DR). The present work was dedicated to the investigation of PHLPP2 in DR through in vivo experiments with rat models induced by intraperitoneal injection of streptozotocin. Compared to normal rats, the retinas of rats with DR exhibited a notable increase in the level of PHLPP2. The reduction of PHLPP2 levels in the retina was achieved by the intravitreal administration of adeno-associated viruses expressing specific shRNA targeting PHLPP2. Decreasing the expression of PHLPP2 ameliorated visual function impairment and improved the pathological changes of retina in DR rats. Moreover, decreasing the expression of PHLPP2 repressed the apoptosis, oxidative stress and proinflammatory response in the retinas of rats with DR. Reduction of PHLPP2 levels led to an increase in the levels of phosphorylated AKT and glycogen synthase kinase-3ß (GSK-3ß). Decreasing the expression of PHLPP2 resulted in increased activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which was reversed by suppressing AKT. Notably, the protective effect of reducing PHLPP2 on DR was eliminated when Nrf2 was restrained. These observations show that the down-regulation of PHLPP2 has protective effects on DR by preserving the structure and function of the retina by regulating the AKT-GSK-3ß-Nrf2 signal cascade. Therefore, targeting PHLPP2 may hold promise in the treatment of DR.

Melatonin antagonizes oxidative stress-induced apoptosis in retinal ganglion cells through activating the thioredoxin-1 pathway.

This study aimed to explore the role of melatonin in oxidative stress-induced injury on retinal ganglion cells and the underlying mechanisms. The immortalized RGC-5 cells were treated with H2O2 to induce oxidative injury. Cell viability was measured by Cell Counting Kit-8, and apoptosis was determined by flow cytometry and western blot assays. Reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels were examined to evaluate oxidative stress levels. In addition, Thioredoxin-1 (Trx1) was silenced in RGC-5 cells using small interfering RNA followed by signaling pathway examination to explore the underlying mechanisms of melatonin in alleviating oxidative injury. Melatonin pre-treatment significantly alleviated H2O2-induced apoptosis in RGC-5 cells. Melatonin also markedly reversed the upregulation of cleaved-caspase 3, cleaved-caspase 9, and Bax expression and downregulation of Bcl-2 expression induced by H2O2. Further analyses presented that melatonin significantly attenuated the increase of ROS, LDH, and MDA levels in RGC-5 cells after H2O2 treatment. Melatonin also abolished the downregulated expression of Superoxide dismutase type 1, Trx1, and Thioredoxin reductase 1, and the reduced activity of thioredoxin reductase in RGC-5 cells after H2O2 treatment. Notably, Trx1 knockdown significantly mitigated the protective effect of melatonin in alleviating H2O2-induced apoptosis and oxidative stress, while administration of compound C, a common inhibitor of c-Jun N-terminal kinase (JNK) signaling, partially reversed the effect of Trx1 silencing, thereby ameliorating the apoptosis and oxidative injury induced by H2O2 in RGC-5 cells. Melatonin could significantly alleviate oxidative stress-induced injury of retinal ganglion cells via modulating Trx1-mediated JNK signaling pathway.

Differential expression and prognostic value of TLR4 in kidney renal clear cell carcinoma.

Human Toll-like receptor (TLR) family plays a crucial role in immunity and cancer progression. However, the specific role of human Toll-like receptor 4 (TLR4) in kidney renal clear cell carcinoma (KIRC) remains obscure. Thus, we used single-cell RNA sequencing (RNA-seq) and bulk RNA-seq data combined with in vitro studies to evaluate the expression and prognostic value of TLR4 in KIRC. In our study, we observed that TLR4 was over expressed in KIRC tissues compared to normal renal tissues. And the expression of TLR4 was higher in macrophages/monocytes than other cell types. Besides, there is a close association between TLR4 expression and immune cell infiltration (Neutrophils, Macrophages, T cells and B cells) in KIRC. Immunohistochemical staining also showed that TLR4 was overexpressed in inflammatory infiltration renal tissue compared with normal tissue. Meanwhile, high expression of TLR4 exhibited correlations with improved survival, lower tumor grade and stage. Interestingly, the protective significance of TLR4 only showed in female patients (HR = 0.37, P < 0.01), other than male patients (HR = 0.71, P = 0.08) with KIRC. Consistently, KIRC samples with lymph node metastasis showed lower expression of TLR4. Knockdown of TLR4 in 786-O cell line increased cell proliferation and clonogenic capacity. In summary, this study found TLR4 could inhibit the progression of kidney cancer and was associated with improved survival in KIRC. The overexpression of TLR4 in macrophages and the close association between TLR4 and immune cell infiltration also underline the critical role of TLR4 in building the immune microenvironment for kidney cancer. These results may offer insights into the mechanism and immune microenvironment of kidney cancer.

Multi-target mechanism of misoprostol in pregnancy termination based on network pharmacology and molecular docking.

Misoprostol is a prostaglandin analogue that contracts the uterus, prompting the expulsion of the embryo. No systematic evaluation of the mechanisms of misoprostol has previously been performed. In this study, known targets of misoprostol were obtained from the DrugBank database; potential targets of misoprostol were predicted using data from the SwissTargetPrediction and PharmMapper databases; and the main targets of pregnancy termination were obtained from the GeneCards database. The protein-protein interaction (PPI) network of the shared genes between misoprostol and pregnancy termination was constructed using data from the STRING database, and the "misoprostol-pregnancy termination-pathway" network was constructed and potential targets was verified through molecular docking. We analyzed 37 shared target genes and obtained a network diagram of 134 potential targets, which the core therapeutic targets were HSP90AA1, EGFR, and MAPK1. GO functional and KEGG pathway enrichment analyses showed that misoprostol can modulate the VEGF signaling pathway, calcium signaling pathway, and NF-κB signaling pathway in pregnancy termination and mainly interferes with protein phosphorylation, cell localization, and protein hydrolysis regulation processes. This research illustrates the mechanism underlying the pharmacological effect of misoprostol, namely pregnancy termination. However, further experimental verification is warranted for optimal use of misoprostol during clinical practice.

Le misoprostol est un analogue des prostaglandines qui contracte l'utérus, provoquant l'expulsion de l'embryon. Aucune évaluation systématique des mécanismes du misoprostol n'a été réalisée auparavant. Dans cette étude, les cibles connues du misoprostol ont été obtenues à partir de la base de données DrugBank ; Les cibles potentielles du misoprostol ont été prédites à l'aide des données des bases de données SwissTargetPrediction et PharmMapper ; et les principales cibles de l'interruption de grossesse ont été obtenues à partir de la base de données GeneCards. Le réseau d'interaction protéine-protéine (IPP) des gènes partagés entre le misoprostol et l'interruption de grossesse a été construit à l'aide des données de la base de données STRING, et le réseau « voie d'interruption de grossesse-misoprostol ¼ a été construit et les cibles potentielles ont été vérifiées par amarrage moléculaire. Nous avons analysé 37 gènes cibles partagés et obtenu un diagramme de réseau de 134 cibles potentielles, dont les principales cibles thérapeutiques étaient HSP90AA1, EGFR et MAPK1. Les analyses d'enrichissement des voies fonctionnelles GO et KEGG ont montré que le misoprostol peut moduler la voie de signalisation VEGF, la voie de signalisation du calcium et la voie de signalisation NF-κB lors de l'interruption de grossesse et interfère principalement avec les processus de phosphorylation des protéines, de localisation cellulaire et de régulation de l'hydrolyse des protéines. Cette recherche illustre le mécanisme sous-jacent à l'effet pharmacologique du misoprostol, à savoir l'interruption de grossesse. Cependant, une vérification expérimentale plus approfondie est justifiée pour une utilisation optimale du misoprostol au cours de la pratique clinique.

Association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects in offspring: a prospective cohort study. / å­•æœŸé‡é‡‘å±žå ƒç´ å’Œå¾®é‡å ƒç´ æ°´å¹³ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— ç›¸å ³æ€§çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To study the association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects (CHD) in offspring, and to establish a model for predicting the probability of CHD based on the levels of heavy metals and trace elements during pregnancy. METHODS: Based on the prospective birth cohort study in Gansu Provincial Maternal and Child Health Hospital in 2010-2012, a nested case-control study was conducted for the follow-up observation of 14 359 pregnant women. Among the pregnant women, 97 pregnant women whose offspring were diagnosed with CHD during follow-up were enrolled as the CHD group, and 194 pregnant women whose offspring had no CHD were selected as the control group. Inductively coupled plasma mass spectrometry was used to measure the levels of heavy metals and trace elements in maternal blood samples and fetal umbilical cord blood samples. A multivariate logistic regression analysis was used to evaluate the association between heavy metal and trace elements and CHD in offspring. A nomogram model for predicting the probability of CHD in offspring was established based on the levels of heavy metals and trace elements during pregnancy. RESULTS: Compared with the control group, the CHD group had significantly higher levels of aluminum (Al), natrium (Na), calcium (Ca), titanium (Ti), selenium (Se), strontium (Sr), stannum (Sn), stibium (Sb), barium (Ba), and thorium (Th) in maternal blood samples (P<0.05), as well as significantly higher levels of Al, zinc (Zn), magnesium (Mg), kalium (K), Ca, Ti, chromium (Cr), copper (Cu), arsenic (As), Se, Sr, argentum (Ag), cadmium (Cd), Sn, and plumbum (Pb) in umbilical cord blood (P<0.05). The multivariate logistic regression analysis showed that the increase in the Sb level in maternal blood was associated with the increase in the risk of CHD in offspring [adjusted odds ratio (aOR)=4.81, 95% confidence interval (CI): 1.65-14.07, P=0.004], while in umbilical cord blood, the high levels of Al (aOR=4.22, 95%CI: 1.35-13.16, P=0.013), Mg (aOR=8.00, 95%CI: 1.52-42.08, P=0.014), and Pb (aOR=3.82, 95%CI: 0.96-15.23, P=0.049) were significantly associated with the risk of CHD in offspring. The levels of Al, Th, and Sb in maternal blood and levels of Al, Mg, and Pb in umbilical cord blood were included in the predictive model for CHD in offspring based on the levels of heavy metals and trace elements during pregnancy, and the calibration curve of the nomogram predictive model was close to the ideal curve. CONCLUSIONS: Increases in the levels of Al, Th, Sb, Mg, and Pb during pregnancy may indicate the increase in the risk of CHD in offspring, and the nomogram predictive model based on these indices can be used to predict the probability of CHD in offspring.

Upregulated CD200 in pre-retinal proliferative fibrovascular membranes of proliferative diabetic retinopathy patients and its correlation with vascular endothelial growth factor.

OBJECTIVE AND DESIGN: The objective was to determine the expression of CD200 in the pre-retinal proliferative fibrovascular membranes (PFVM) of patients with proliferative diabetic retinopathy (PDR) and to clarify its correlation with vascular endothelial growth factor (VEGF) and corresponding receptors. METHODS: PFVM samples were collected by vitrectomy from 14 patients with PDR, and 11 non-diabetic patients who accepted vitrectomy for idiopathic epiretinal membranes removal. The expression of CD200, VEGF,VEGF-R1 and VEGF-R2 was measured via qPCR and immunofluorescent staining. RESULTS: The mRNA level of CD200 was significantly higher in PDR patients than that in control patients. Meanwhile, CD200 and CD31 were found co-located and statistically associated in PFVM of PDR patients. The mRNA levels of VEGF, VEGF-R1 and VEGF-R2 were also significantly higher in PDR patients. Moreover, statistical association was found between CD200 and VEGF, VEGF-R1 in mRNA levels. But there was no significant correlationship between CD200 and VEGF-R2. CONCLUSIONS: These results suggest a significantly increased expression of CD200 in PFVM of patients with PDR and present a crucial association between CD200 and VEGF-involved pathway. It represents a potential therapy that interfering with CD200 may inhibit the VEFG expression and neovascular formation in PDR patients.

Anti-angiogenic and anti-inflammatory effects of CD200-CD200R1 axis in oxygen-induced retinopathy mice model.

OBJECTIVE: In this study, the expression changes and the potential effects of CD200 and its receptors during the process of retinal neovascularization (RNV) development had been detected, using a classic oxygen-induced retinopathy (OIR) mice model and CD200Fc (a CD200R1 agonist) intravitreal injection. MATERIALS AND METHODS: 7 day postnatal (P7) C57BL/6J mice were raised in hyperoxia incubators with 75±2% oxygen for 5 days, and returned to room air at P12. All animals were subdivided into three groups: normoxia control, OIR, and OIR+CD200Fc group. The mice of OIR+CD200Fc group were intravitreal injected with CD200Fc (2µg/µL, 0.5µL) at P12. Retinas and vitreous samples were harvested at P17. The expression and localization of CD200 and its receptors were analyzed by Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and retinal whole-mount immunofluorescence. To investigate the effects of CD200Fc treatment, vascular endothelial growth factor (VEGF)-A, platelet-derived growth factor (PDGF)-BB, pro-inflammatory cytokines, NV area, and microglial activation were detected respectively. RESULTS: In OIR group, both protein and RNA levels of CD200 and CD200R1 were significantly up-regulated. The increased CD200 and CD200R1 were co-localized with Alex594-labeled Griffonia simplicifolia isolectin B4 (IB4) on vascular endothelial cells in NV area of OIR samples, and CD200R1 was co-expressed with ionized calcium-bind adapter molecule 1 (iba1) on microglia in OIR samples at the same time. CD200Fc intravitreal injection could significantly reduce the release of VEGF-A, PDGF-BB, and pro-inflammatory cytokines; shrink the NV area; and inhibit the activation of microglia in OIR mice. CONCLUSION: These findings suggested that the up-regulation of CD200 and CD200R1 was closely related to RNV development, and the antiangiogenic effects of CD200Fc in OIR model might be realized by inhibition of inflammatory response and microglia activation. The results may provide a new therapeutic target for RNV diseases.

MicroRNA-362-3p attenuates motor deficit following spinal cord injury via targeting paired box gene 2.

Spinal cord injury is a disabling disorder, leading to neurological impairments. Although some microRNAs have been reported to be associated with spinal cord injury, the function of microRNA-362-3p, as one of downregulated miRNAs after spinal cord injury, is still unclear. In current study, spinal cord injury models were established. Then, we performed microRNA-362-3p overexpression in spinal cord injury rats, which expressed the low microRNA-362-3p. Results from behavioral testing, hematoxylin and eosin staining and Nissl staining revealed that microRNA-362-3p over expresssion improved the functional resoration in spinal cord injury rats. Furthermore, it caused the decrease of neuronal apoptosis and inhibition of the neuronal inflammation in these rats. Besides, Paired box gene 2 was verified as a target gene of microRNA-362-3p using luciferase assay, which predicted via bioinformatics technology. Moreover, microRNA-362-3p alleviated the neuralgia and reduced the activation of ERK and p38 through inhibition of Paired box gene 2. In conclusion, the findings demonstrated that microRNA-362-3p attenuated neuropathic pain following spinal cord injury through targeting Paired box gene 2. It provides us the new biomarker to diagnose and monitor spinal cord injury.

Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF-1α-VEGF pathway in oxygen-induced retinopathy mice.

Retinopathy of prematurity (ROP) is a retinopathy characterized by retinal neovascularization (RNV) occurring in preterm infants treated with high concentrations of oxygen and may lead to blindness in severe cases. Currently, anti-VEGF therapy is a major treatment for ROP, but it is costly and may cause serious complications. The previous study has demonstrated that melatonin exerted neuroprotective effect against retinal ganglion cell death induced by hypoxia in neonatal rats. However, whether melatonin is anti-angiogenic and neuroglial protective in the progression of ROP remains unknown. Thus, this study was to investigate the effect of melatonin on RNV and neuroglia in the retina of oxygen-induced retinopathy (OIR) mice. The results showed a reduction in retinal vascular leakage in OIR mice after melatonin treatment. Besides, the size of retinal neovascular and avascular areas, the number of preretinal neovascular cell nuclei, and the number of proliferative vascular endothelial cells within the neovascular area were significantly decreased in mice treated with melatonin. After oxygen-induced injury, the density of astrocytes was decreased, accompanied by morphologic and functional changes of astrocytes. Besides, retinal microglia were also activated. Meanwhile, the levels of inflammatory factors were elevated. However, these pathologic processes were all hindered by melatonin treatment. Furthermore, HIF-1α-VEGF pathway was activated in the retina of OIR mice, yet was suppressed in melatonin-treated OIR mice retinas. In conclusion, melatonin prevented pathologic neovascularization, protected neuroglial cells, and exerts anti-inflammation effect via inhibition of HIF-1α-VEGF pathway in OIR retinas, suggesting that melatonin could be a promising therapeutic agent for ROP.

CD200R promotes high glucose-induced oxidative stress and damage in human retinal pigment epithelial cells by activating the mTOR signaling pathway.

Diabetic retinopathy (DR) is established as the primary cause of visual impairment and preventable blindness, posing significant social and economic burdens on healthcare systems worldwide. Oxidative stress has been identified as a major contributor to DR, yet the precise role of the transmembrane glycoprotein CD200R in this context remains elusive. We studied human retinal pigment epithelia ARPE-19 cells to investigate the role of CD200R in high-glucose (HG) induced oxidative stress. Under HG conditions, we found a significant increase in CD200R expression in a time-dependent pattern. Conversely, knockdown of CD200R effectively alleviated oxidative stress and restored cell viability in HG-treated ARPE-19 cells, a phenomenon corroborated by the addition of a reactive oxygen species (ROS) scavenger. Exploration of the AKT/mTOR signaling pathway confirmed its mediating role regarding CD200R knockdown suppression of the expression of key proteins induced by HG conditions. Additionally, we found that the inhibition of mTOR signaling with Rapamycin effectively countered HG-induced oxidative stress in ARPE-19 cells, suggesting a promising therapeutic target against oxidative stress in the context of DR. This study establishes the crucial role of CD200R in HG-induced oxidative stress and identifies potential therapeutic avenues for the treatment of DR.

Setanaxib mitigates oxidative damage following retinal ischemia-reperfusion via NOX1 and NOX4 inhibition in retinal ganglion cells.

Glaucoma, a prevalent cause of permanent visual impairment worldwide, is characterized by the progressive degeneration of retinal ganglion cells (RGCs). NADPH oxidase (NOX) 1 and NOX4 are pivotal nodes in various retinal diseases. Setanaxib, a potent and highly selective inhibitor of NOX1 and NOX4, can impede the progression of various diseases. This study investigated the efficacy of setanaxib in ameliorating retinal ischemia-reperfusion (I/R) injury and elucidated its underlying mechanisms. The model of retinal I/R induced by acute intraocular hypertension and the oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary RGCs were established. By suppressing NOX1 and NOX4 expression in RGCs, setanaxib mitigated I/R-induced retinal neuronal loss, structural disruption, and dysfunction. Setanaxib reduced TUNEL-positive cells, upregulated Bcl-2, and inhibited Bax, Bad, and cleaved-caspase-3 overexpression after I/R injury in vitro and in vivo. Moreover, setanaxib also significantly reduced cellular senescence, as demonstrated by downregulating SA-ß-gal-positive and p16-INK4a expression. Furthermore, setanaxib significantly suppressed ROS production, Hif-1α and FOXO1 upregulation, and NRF2 downregulation in damaged RGCs. These findings highlight that the setanaxib effectively inhibited NOX1 and NOX4, thereby regulating ROS production and redox signal activation. This inhibition further prevents the activation of apoptosis and senescence related factors in RGCs, ultimately protecting them against retinal I/R injury. Consequently, setanaxib exhibits promising potential as a therapeutic intervention for glaucoma.

Orbital liposarcoma: a retrospective, single-center study of thirteen patients.

AIM: To explore the clinical and pathological characteristics of thirteen patients with orbital liposarcoma. METHODS: The clinical history data of thirteen patients diagnosed as orbital liposarcoma at Beijing Tongren Hospital, from 2006 to 2021 were collected and analyzed. The data includes age, gender, affected orbital side, course of disease, status of disease (primary or recurrent), clinical manifestations, preoperative visual acuity, operative treatment, the relations between liposarcoma and surrounding tissue, longest diameter of liposarcoma, histological subtype, immunohistochemical indicators, follow-up treatment and prognosis. RESULTS: The initial symptoms are diverse. Proptosis is the most frequent chief complaint and the others included vision loss, epiphora, diplopia, and eyelid palpable mass. Results of imaging examination [computed tomography (CT) or magnetic resonance imaging (MRI)] showed orbital mass. In terms of treatment, 10 patients received tumor resection, and the mean longest diameter of the tumor was 3.39±1.36 cm. The other 3 patients had optic nerve invaded, so they received orbital exenteration. Pathological examination results confirmed the diagnose of liposarcoma for 13 patients. Six patients displayed as myxoid type, and three patients in each type of dedifferentiated and well-differentiated type. One patient was verified as pleomorphic, which was a rare type of liposarcoma. All of the patients showed Vimentin positive, and most showed CD34 and S-100 positive. Besides, four patients showed smooth muscle actin positive. All thirteen patients were alive. CONCLUSION: Orbital liposarcoma is a rare disease and it has no specific clinical manifestation. The diagnosis of liposarcoma should be considered when proptosis and orbital mass occurred in orbit. It is recommended to perform pathological examination to achieve early detection and early treatment.

Analysis of clinical and pathological features of ciliary body medulloepithelioma.

AIM: To analyze and summarize the clinical and pathological features of ciliary body medulloepithelioma. METHODS: The clinical and pathological data of 11 patients (11 eyes) who were diagnosed with ciliary body medulloepithelioma at Beijing Tongren Hospital, Capital Medical University, from 2007 to 2021 were retrospectively analyzed. RESULTS: The initial symptoms of 11 patients included vision loss (6 eyes), atrophia bulbi (1 eye), proptosis (2 eyes), and leukocoria (2 eyes). Most patients suffered with corneal opacity, anterior chamber flare and hyphema. Iris neovascularization and synechia, complicated cataract, and secondary glaucoma occurred in several cases. Three patients even had lens subluxation and retinal detachment. B-scan ultrasonography showed vitreous opacity and a medium-high uneven echo mass in the eyeball. Ultrasound biomicroscopy examination showed a spherical or hemispherical ciliary body mass with uneven internal echoes and irregular cystic spaces. All of the 11 patients were diagnosed with malignant ciliary body medulloepithelioma by pathological evidence. In this study, 6 patients had enucleation (2 patients had systemic chemotherapy after surgery), and the other 5 patients had local tumor resection (1 patient had plaque radiotherapy after surgery). CONCLUSION: Ciliary body medulloepithelioma is a rare intraocular tumor and may be easily confused with retinoblastoma. Analyzing the clinical and pathological features of ciliary body medulloepithelioma is useful to further understand ciliary body medulloepithelioma, and can make an accurate diagnosis and better treatment.

Effect of Pro-kin visual feedback balance training on balance function of individuals with early Parkinson's disease: a randomized controlled pilot trial.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease. Patients often present with balance dysfunction. Several studies have applied visual feedback training to stroke patients and demonstrated significant improvement. However, the application of visual feedback balance training in PD patients has not been reported. Objective: To observe the effects of visual feedback balance training combined with conventional rehabilitation training on the balance function of patients with early PD. Methods: Fifty patients with early PD were randomly divided into control group and observation group. The control group received conventional rehabilitation training, including body position transfer, weight shifting, movement in all directions and gait training. The observation group were added with visual feedback balance training on the basis of the training above. All patients were trained 5 times per week for 4 weeks. Berg Balance Scale (BBS), Time Up-and-Go test (TUG) and Pro-Kin balance training instrument were used to evaluate the balance function of patients before and after treatment, and the balance function were compared between the two groups. Results: The BBS and TUG scores of the observation group and the control group were improved significantly (P<0.01), and the BBS and TUG scores of the observation group were improved more obviously than control group (P<0.01). The length and area of eye open and closed condition in the observation group and the control group were significantly reduced compared with those before training (P<0.01), and the degree of reduction in the observation group was more obvious (P<0.01). The length and area of the observation group and the control group before and after training when eye open were smaller than those when eye closed (P<0.01). Conclusion: The conventional rehabilitation therapy can improve the balance function of PD patients, but the combination of visual feedback balance training and conventional rehabilitation therapy can improve the balance function more significantly.

Effects of perioperative managements on ocular surface microbiota in intravitreal injection patients.

AIM: To investigate the effects of on ocular surface microbiota in patients who received intravitreal injections. METHODS: Samples of ocular surface microbiota were obtained from 41 eyes of 41 patients who visited the Department of Ophthalmology. Patients were separated for three groups. Group A did not receive perioperative managements or intravitreal injection. Group B1 received only once and B2 received more than twice. In operating room, the samples were collected on the ocular surface. Operating taxonomic units (OTUs) clustering and alpha/beta diversity analysis was performed. The microbial 16S rRNA from samples were analyzed using the HiSeq 2500 platform. RESULTS: Alpha diversity did not differ in each group, and beta diversity differed in the B2 group. Beta diversity showed a significant difference between Group A and B2 (P=0.048). With the perioperative managements before intravitreal injection, the composition and relative abundance were altered. Top 10 microbiota on phylum and genus level, and then microbiota notably changed at genus level were listed. Gram-negative bacteria were varied more. Furthermore, Proteus was not found in Groups A and B1, but it was appeared after the patients received perioperative management and intravitreal injections in Group B2. CONCLUSION: With the perioperative managements, the balance of microbiota on the ocular surface is destroyed, and relative composition and abundance of microbiota on the ocular surface is obviously altered. The clinical doctors should pay more attention on the consequence of perioperative managements before intravitreal injection.

Synthesis and Biological Activity Evaluation of 2-Cyanopyrrole Derivatives as Potential Tyrosinase Inhibitors.

In order to find potential inhibitors of tyrosinase, two series of pyrrole derivatives A (1-17) and B (1-8) were synthesized and screened for their inhibitory activities on tyrosinase. Most of the 2-cyanopyrrole derivatives exhibited effective inhibitory activities. In particular, A12 exhibited the strongest inhibitory activities, with the IC50 values of 0.97 µM, which is ∼30 times stronger than the reference inhibitor kojic acid (IC50: 28.72 µM). The inhibitory mechanism analysis results revealed that A12 was a reversible and mixed-type inhibitor. Molecular docking experiments clarified the interaction between A12 with tyrosinase. Furthermore, A12 (100 µM) presented effective inhibitory effect on tyrosinase in B16 melanoma cells with inhibition of 33.48%, which was equivalent to that of Kojic acid (39.81%). Accordingly, compound A12 may serve as the lead structure for the further design of potent tyrosinase inhibitors. Molecular docking studies confirmed the interaction between the compound and tyrosinase.

Aqueous humor monocyte chemoattractant protein-1 predicted long-term visual outcome of proliferative diabetic retinopathy undergone intravitreal injection of bevacizumab and vitrectomy.

PURPOSE: We aim to investigate the risk factors associated with the prognosis of proliferative diabetic retinopathy (PDR) after a sequential treatment of intravitreal injection of bevacizumab (IVB) and pars plana vitrectomy (PPV). METHODS: In this cohort study, 63 eyes from 55 patients (21 females) diagnosed with PDR, who needed PPV for non-clearing vitreous hemorrhage or fibrovascular membrane proliferation were enrolled. All the eyes underwent IVB followed by PPV. Anterior chamber tap was performed at the beginning of both procedures to evaluate the concentration of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1. RESULTS: Forty-seven patients (54 eyes) were followed over six months, averaging 12±5 (6-19) months. The concentration of VEGF significantly decreased after IVB (P<0.001), while other cytokines did not change significantly. The aqueous humor level of IL-8 after IVB (R = 0.378, P = 0.033), MCP-1 before (R = 0.368, P = 0.021) and after (R = 0.368, P = 0.038) IVB, and combined phacoemulsification (R = 0.293, P = 0.032) was correlated with the logMAR visual acuity at the last follow-up. Multivariate analysis showed that MCP-1 was the predictor for a worse visual outcome (B = 0.108, 95% CI 0.013-0.202; P = 0.027). CONCLUSIONS: MCP-1 was a predictor for the unfavorable visual outcome of PDR after IVB pretreatment and PPV.

Comparison of the Ocular Microbiomes of Dry Eye Patients With and Without Autoimmune Disease.

Purpose: The pathogenesis of dry eye concomitant with autoimmune disease is different from that of dry eye without autoimmune disease. The aim of this study was to explore differences in the microbiota diversity and composition in dry eye with and without autoimmune disease. Methods: Swab samples from the inferior fornix of the conjunctival sac were obtained from dry eye patients without autoimmune disease (n = 49, dry eye group) and from those with autoimmune disease (n = 38, immdry eye group). Isolated bacterial DNAs from swabs were analyzed with 16S rRNA amplicon sequencing. Results: Analysis of the alpha diversity revealed no significant differences between subjects in the dry eye and immdry eye groups. Those in the immdry eye group had a distinct microbial composition compared with those in the dry eye group. The combination of the genera Corynebacterium and Pelomonas distinguished subjects in the immdry eye group from those in the dry eye group, with an area under the curve of 0.73 (95% CI = 0.62-0.84). For the same bacteria, the correlations between microbe abundance and the ocular surface parameters were different in the two groups. In addition, the functions of the microbial communities were altered in the two groups. Conclusions: Our study demonstrates changes in the composition and function of the ocular microbiome between subjects in the immdry eye and dry eye groups, which suggests that the potential pathogenesis is different.

Efficacy of wet-lab training versus surgical-simulator training on performance of ophthalmology residents during chopping in cataract surgery.

AIM: To analyze whether wet-lab training (WLT) or surgical-simulator training (SST) is better for ophthalmology residents to master the chopping technique. METHODS: Sixty ophthalmology residents (in their second year) and three cataract surgeons participated in the study. The residents were randomly separated into two groups, WLT group and SST group. The residents in WLT group were asked to perform 10 trials of chopping using pig eyes and scored by the surgeons, and then they performed and scored using simulator for one time. The residents in SST group underwent 10 trials of chopping using simulator, and the simulator scored each trail. Then, this group were asked to perform the chopping using pig eyes and scored by the surgeons. At last, we investigated the residents' satisfaction about the training. RESULTS: The demographic characteristics had no significant differences between the two groups. Recorded by the simulator, the residents in SST group got significantly higher overall score (83.90±1.31) than WLT group (78.73±1.92, P=0.03). And the residents in SST group got less corner area injured, and they spend less time than WLT group (P<0.05). Moreover, the residents in WLT group used more ultrasonic energy value than SST group (P=0.03). However, scored by the surgeons, the residents in two groups got nearly the same overall score. The residents in WLT group performed better on the frequencies of posterior capsule torn and incisional stress (P=0.03, 0.008, respectively). In the survey, the residents in two groups held the same opinion that the training was helpful and they strongly recommended this training. And all of them enjoyed the training, and enjoyed being randomized in their own group. However, with respect to the realistic character, the residents thought that WLT was better than SST (P<0.001). CONCLUSION: Both of the Eyesi surgical-stimulator and the wet-lab improve the residents' chopping ability and each has its own advantages. The combination of the two training ways could be considered to be a part of the training curriculum for new residents.