O-GlcNAcylation Inhibition Upregulates Connexin43 Expression in the Endothelium to Protect the Tight Junction Barrier in Diabetic Retinopathy.

Purpose: This study aimed to investigate the effects of O-linked N-acetylglucosamine modification (O-GlcNAcylation) on connexin43 (Cx43) expression and its subsequent effects on tight junction properties in diabetic retinopathy (DR). Methods: O-GlcNAcylation levels in primary human retinal vascular endothelial cells (HRVECs) and retinas from rats with diabetes were regulated by treatment with Thiamet G or alloxan. Immunoprecipitation was used to examine the relationship between O-GlcNAcylation and Cx43 expression. Stable overexpression and knockdown of Cx43 in HRVECs were achieved using lentivirus constructs; further, their effects on occludin and zonula occluden-1 (ZO-1) expression and tight junction barrier function were determined. Results: O-GlcNAcylation level increased significantly, whereas Cx43 expression decreased in retinas from rats with diabetes and HRVECs cultured under high-glucose conditions. Immunoprecipitation revealed that Cx43 was modified by O-GlcNAcylation and phosphorylation simultaneously. O-GlcNAcylation inhibition negatively regulated both total Cx43 and phosphorylated Cx43 expression, subsequently disrupting tight junction properties. Conversely, Cx43 overexpression reversed the disruption of tight junction properties and downregulated vascular endothelial growth factor expression. Consistently, Cx43 overexpression increased transendothelial electrical resistance values in HRVEC layers. Conclusions: O-GlcNAcylation negatively regulated Cx43 expression, contributing to the disruption of the blood retinal barrier. However, O-GlcNAcylation inhibition and Cx43 overexpression could reverse the tight junction disruption. Therefore, O-GlcNAcylation inhibition is a potential target for avoiding tight junction disruption through the Cx43 pathway in DR.

Multi-Parameter Auto-Tuning Algorithm for Mass Spectrometer Based on Improved Particle Swarm Optimization.

Quadrupole mass spectrometers (QMS) are widely used for clinical diagnosis and chemical analysis. To obtain the best experimental results, mass spectrometers must be calibrated to an ideal setting before use. However, tuning the current QMS is challenging. Traditional tuning techniques possess low automation levels and rely primarily on skilled engineers. Therefore, in this study, we propose an innovative auto-tuning algorithm for QMS based on the improved particle swarm optimization (PSO) algorithm to automatically find the optimal solution of QMS parameters and make the QMS reach the optimal state. The improved PSO algorithm is combined with simulated annealing, multiple inertia weights, dynamic boundaries, and other methods to prevent the traditional PSO algorithm from the issue of a local optimal solution and premature convergence. According to the characteristics of the mass spectrum peaks, a termination function is proposed to simplify the termination conditions of the PSO algorithm and further improve the automation level of the mass spectrometer. The results of auto-calibration testing of resolution and mass axis show that both resolution and mass axis calibration could effectively meet the requirements of mass spectrometry experiments. By the experiment of auto-optimization testing of lens and ion source parameters, these parameters were all in the vicinity of the optimal solution, which achieved the expected performance. Through numerous experiments, the reproducibility of the algorithm was established as meeting the auto-tuning function of the QMS. The proposed method can automatically tune the mass spectrometer from its non-optimal condition to the optimal one, which can effectively reduce the tuning difficulty of QMS.

Assessment interocular symmetry of peripapillary vessel density in young myopes with optical coherence tomographic angiography.

PURPOSE: The purpose of our study was to evaluate the interocular symmetry and distribution of peripapillary vessel density in young myopic eyes. METHODS: A cross-sectional observational study was designed. A total of 174 eyes of 87 young myopic patients were recruited in this study. According to spherical equivalent (SE), 48 eyes were classified as mild myopia with a mean SE of - 2.12D (SD 0.66D), 66 as moderate myopia with a mean SE of - 4.50D (SD 0.87D), and 60 as high myopia with a mean SE of - 7.39D (SD 1.30D). Optical coherence tomography angiography (OCTA) was used to measure the vessel density. The distribution and interocular symmetry of peripapillary vessel densities were analyzed. RESULTS: The vessel densities in the whole image, peripapillary, superior and inferior sectors were significantly lower in the high myopia group than in the mild or moderate myopia group (All P < 0.001), and the density in the nasal sector was significantly lower in the high myopia group than in the mild group. And most interesting, the vessel densities in the inside disc and temporal sector showed no difference among the three myopic groups (All P > 0.05). By Pearson correlation analysis, the vessel densities in the whole image, peripapillary, superior, inferior and nasal sectors were negatively correlated with axial length (AL) and SE (All P < 0.001), but vessel densities in the inside disc and temporal sector did not show this correlation (All P > 0.05). Interocular symmetry was observed in all the vascular parameters through paired-samples t-tests (All P > 0.05), intraclass correlation coefficient (ICC) and Pearson correlation analysis (All P < 0.001). CONCLUSION: The density of radial peripapillary capillaries decreased in the myopic eye with axial elongation, and optical vascular parameters showed significant interocular symmetry among young myopic eyes.

Association between urinary nickel with obesity status in adults: A cross-sectional study.

Objectives: The prevalence of obesity is on the rise and is connected to numerous factors. However, the relationship between obesity and nickel has never been investigated. Our study aimed to explore the association between urinary nickel and obesity Status in adults. Methods: From the 2017-2018 National Health and Nutrition Examination Surveys (NHANES), 1,705 participants ≥18 years of age were enrolled. To explore further the relationship among urinary nickel, body mass index (BMI), and waist circumference(WC), Weighted multivariate linear regression analyses and further subgroup analyzes were conducted. Results: Urinary nickel does not correlate with BMI level but positively correlates with WC. In the subgroup analyzed according to sex, Urinary nickel has a positive correlation with BMI and WC in males but has a negative correlation in females. Secondary stratification analysis according to sex and race, Urinary nickel positively correlates with BMI in White males. It also positively correlates with WC in both White and Black males. Conclusions: A correlation was found between urinary nickel levels and BMI and WC in adult males. Adult men, especially those already obese, may need to reduce nickel exposure.

Biocompatibility and osteoinductive ability of casein phosphopeptide modified polyetheretherketone.

Polyetheretherketone (PEEK) is a potential implant material for dental application due to its excellent mechanical properties. However, its biological inertness and poor osteoinductive ability limited its clinical application. Based on a lay-by-layer self-assembly technique, here we incorporated casein phosphopeptide (CPP) onto PEEK surface by a simple two-step strategy to address the poor osteoinductive ability of PEEK implants. In this study, the PEEK specimens were positively charged by 3-ammoniumpropyltriethoxysilane (APTES) modification, then the CPP was adsorbed onto the positively charged PEEK surface electrostatically to obtain CPP-modified PEEK (PEEK-CPP) specimens. The surface characterization, layer degradation, biocompatibility and osteoinductive ability of the PEEK-CPP specimens were studied in vitro. After CPP modification, the PEEK-CPP specimens had a porous and hydrophilic surface and presented enhanced cell adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. These findings indicated that CPP modification could significantly improve the biocompatibility and osteoinductive ability of PEEK-CPP implants in vitro. In a word, CPP modification is a promising strategy for the PEEK implants to achieve osseointegration.

Primary membranous nephrotic syndrome with chylothorax as first presentation: A case report and literature review.

BACKGROUND: Primary membranous nephrotic syndrome with chylothorax as the first manifestation is an unusual condition. To date, only a few cases have been reported in clinical practice. CASE SUMMARY: The clinical data of a 48-year-old man with primary nephrotic syndrome combined with chylothorax admitted to the Department of Respiratory and Critical Care Medicine of Shaanxi Provincial People's Hospital were retrospectively analysed. The patient was admitted to the hospital for 12 d due to shortness of breath. Imaging showed pleural effusion, laboratory tests confirmed true chylothorax, and renal biopsy revealed membranous nephropathy. After primary disease treatment and early active symptom treatment, the prognosis of the patient was good. This case suggests that chylothorax is a rare complication of primary membranous nephrotic syndrome in adults, and early lymphangiography and renal biopsy can assist in the diagnosis when there are no contraindications. CONCLUSION: Primary membranous nephrotic syndrome combined with chylothorax is rare in clinical practice. We report a relevant case to provide case information for clinicians and to improve diagnosis and treatment.

Gallic acid regulates immune response in a mouse model of rheumatoid arthritis.

INTRODUCTION: Previous studies revealed that gallic acid (GA) exerts anti-inflammation and immuno-regulatory properties. This study aims to explore the pharmacological activities of GA in collagen-induced arthritis (CIA) mouse model. METHODS: Male DBA/1J mice were used to construct the CIA model. The mice were administrated with GA for 3 weeks. Clinical arthritis scores and hind paw volume were evaluated over the experimental period. qPCR and Western blot analysis were used to determine the levels of matrix metallopeptidases (MMPs) and cytokines. In addition, flow cytometry was used to measure the populations of Th17 and Treg cells. ELISAs were used to determine the cytokines in the serum and ankle joint tissues. RESULTS: Treatment of GA (40 and 80 mg/kg/d) reduced clinical arthritis scores and hind paw volume in the CIA mouse model. Besides, treatment of GA reduced the overexpression of MMPs and modulated the dysregulation of inflammation-related cytokines. Flow cytometry showed that treatment of GA decreased the population of Th17 cells, and increased the population of Treg cells, as supported by treatment of GA regulated the Th17/Treg-related cytokines. CONCLUSIONS: GA attenuates symptoms in the CIA mouse model by anti-inflammation and regulating Th17/Treg cell imbalance.

TSPAN4-positive migrasome derived from retinal pigmented epithelium cells contributes to the development of proliferative vitreoretinopathy.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is a blind-causing disease initiated by the activation of retinal pigmented epithelium (RPE) primarily induced by TGF-ß families. Migrasome is a recently discovered type of extracellular vesicle related to cell migration. RESULTS: Here, we used ex vivo, in vitro, and in vivo models, to investigate the characteristics and functions of migrasomes in RPE activation and PVR development. Results indicated that the migrasome marker tetraspanin-4 (TSPAN4) was abundantly expressed in human PVR-associated clinical samples. The ex vivo model PVR microenvironment is simulated by incubating brown Norway rat RPE eyecups with TGF-ß1. Electron microscope images showed the formation of migrasome-like vesicles during the activation of RPE. Further studies indicated TGF-ß1 increased the expression of TSPAN4 which results in migrasome production. Migrasomes can be internalized by RPE and increase the migration and proliferation ability of RPE. Moreover, TSPAN4-inhibited RPE cells are with reduced ability of initiating experimental PVR. Mechanically, TSPAN4 expression and migrasome production are induced through TGF-ß1/Smad2/3 signaling pathway. CONCLUSION: In conclusion, migrasomes can be produced by RPE under PVR microenvironment. Migrasomes play a pivotal role in RPE activation and PVR progression. Thus, targeting TSPAN4 or blocking migrasome formation might be a new therapeutic method against PVR.

Dual-Functional Polyetheretherketone Surface with an Enhanced Osteogenic Capability and an Antibacterial Adhesion Property In Vitro by Chitosan Modification.

A chitosan layer was covalently bonded to a polyetheretherketone (PEEK) surface using a simple facile self-assembly method to address inadequate biological activity and infection around the implant. The surface characterization, layer degradation, biological activity, and antibacterial adhesion properties of chitosan-modified PEEK (PEEK-CS) were studied. Through chitosan grafting, the surface morphology changed, the surface roughness increased, and the contact angle decreased significantly. PEEK-CS boosted cell adhesion, proliferation, increased alkaline phosphate activity, extracellular matrix mineralization, and expression of osteogenic genes. PEEK-CS demonstrated less adhesion to Porphyromonas gingivalis as well as less bacterial adhesion to P. gingivalis and Streptococcus mutans. According to our findings, chitosan modification significantly improved the osteogenic ability and antibacterial adhesion of PEEK in vitro.

The prevalence and clinical correlates of suicide attempts in comorbid subclinical hypothyroidism in patients with never-treated major depressive disorder in China.

BACKGROUND: Previous studies have emphasized the possible association between subclinical hypothyroidism (SCH) and major depressive disorder (MDD). This study aimed to further investigate suicide attempts and their clinical correlates in MDD patients with comorbid SCH. METHODS: This cross-sectional study recruited 1706 eligible MDD outpatients. The Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression of Severity Scale (CGI-S) were applied to evaluate mental status. Fasting blood samples were collected to examine thyroid function. SCH was defined as thyroid stimulating hormone (TSH) > 8 mIU/L with normal free thyroxine levels. RESULTS: The prevalence of suicide attempts in the SCH group (51.7 %) was significantly higher than that in the non-SCH group (15.4 %; p < 0.001). Logistic regression showed that patients with comorbid SCH were 1.81 times more likely to have attempted suicide as compared with those without (p = 0.001). Among those with TSH > 8 mIU/L, patients with severe anxiety were 3.57 times more likely to attempt suicide compared with those without (p < 0.01). Logistic regression also showed that the CGI-S score (p < 0.001) was independently associated with suicide attempts, while TSH level was not. CONCLUSIONS: SCH comorbidity may pose a specific hazard in MDD patients due to increased suicide attempts. Exhibiting severe anxiety, overall severity of depressive and psychotic symptoms, but not TSH levels, may be independently correlated with suicide attempts in MDD patients with TSH > 8 mIU/L.

Effect of Exercise on the Cognitive Function of Older Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background: Aging and type 2 diabetes mellitus (T2DM) are important risk factors for the development of cognitive deterioration and dementia. The objective of this research was to investigate the effects of an exercise intervention on cognitive function in older T2DM patients. Methods: Eight literature databases (PubMed, EBSCO, Scopus, Embase, The Cochrane Library, Web of Science, Ovid, and ProQuest) were searched from inception to 20 January 2022. The researchers examined randomized controlled trials (RCTs) that evaluated the impact of exercise on the cognitive performance of older T2DM patients. The Cochrane risk-of-bias tool (ROB 2) for RCTs was used to assess each study. The quality of evidence was assessed using the GRADE (grading of recommendations, assessment, development, and evaluations) approach. The mini-mental state examination (MMSE), Modified MMSE (3MSE), and Montreal cognitive assessment (MoCA) were used to evaluate the cognitive outcomes. We performed a subgroup analysis with stratification according to exercise intervention modality, duration, and cognitive impairment. Results: Five trials were eligible, with a total of 738 T2DM patients. The combined findings revealed that exercise improved global cognitive function significantly (standardized mean difference: 1.34, 95% confidence interval: 0.23-2.44, p < 0.01). The effect of exercise on global cognitive performance was not significantly influenced by intervention modality, intervention duration, or cognitive impairment in the sub-group analysis (p > 0.05). In the studies that were included, no relevant adverse events were reported. Conclusion: Exercise is beneficial in improving global cognitive function in older adults with T2DM. Studies with bigger sample sizes and higher quality are additionally expected to draw more definite conclusions. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42022296049].

E-cadherin to N-cadherin switching in the TGF-ß1 mediated retinal pigment epithelial to mesenchymal transition.

A serious form of ocular fibrotic disease is proliferative vitreoretinopathy (PVR) that can ultimately lead to blindness. While the pathogenesis of PVR is known to be closely tied to retinal pigment epithelial (RPE) cell epithelial-mesenchymal transition (EMT) characterized by E-cadherin downregulation and N-cadherin upregulation. Herein, we developed a model of transforming growth factor-ß1 (TGF-ß1)-induced EMT using human RPE (hRPE) cells as a tool for exploring the mechanistic basis for E-cadherin to N-cadherin switching. This analysis revealed that the loss of E-cadherin led to the separation of ß-catenin from the catenin-cadherin complex whereupon it underwent nuclear entry to activate zinc finger E-box binding homeobox 1 (ZEB1), in turn promoting N-cadherin upregulation in this biological context. E-cadherin overexpression was sufficient to inhibit this EMT process and proliferation in RPE cells, further constraining their TGF-ß1-induced apoptosis.

Anti-scarring effect of sodium hyaluronate at filtration pathway after filtering surgery in rabbits.

AIM: To investigate the anti-scarring effect of sodium hyaluronate (HA) at filtration pathway after filtering surgery in a rabbit model. METHODS: Fifteen healthy adult New Zealand white rabbits were selected for trabeculectomy in both eyes. The right eyes were used as HA group with 0.1 mL HA injected into the anterior chamber at the end of the operation; the left eyes were used with 0.1 mL sodium lactate Ringer's solution (RS) injected into the anterior chamber as RS group. Intraocular pressure (IOP), filtering blebs morphology, inflammatory reaction and complications were observed at the 7, 60, and 90d after surgery. RESULTS: One day after surgery, the IOP of HA and RS groups were 12.75±1.92 and 10.50±1.59 mm Hg (P=0.005). At the 7th day postoperative, the filtering blebs of each group were functional type and TGF-ß expression was significantly difference in both groups (0.10±0.01 vs 0.14±0.02, P=0.024). After 60d of the operation, all filtering blebs were scarring and alpha-smooth muscle actin (α-SMA) expression was significantly difference in both groups (0.40±0.04 vs 0.35±0.02, P=0.032). α-SMA positive cells were mainly distributed in the junction of conjunctiva and sclera and around the blood vessels. The collagen volume fraction (CVF) of HA and RS group was (75.49±7.01)% and (79.93±5.35)% (P=0.044). On the 90th day after the operation, CVF was (82.57±5.19)% and (88.08±1.75)% in HA and RS groups (P=0.036). There was no α-SMA positive cell in HA group, while a few positive cells were observed in RS group (P=0.000). CONCLUSION: HA has effect of anti-scar and anti-inflammation on filtration pathway after filtering surgery within 3mo by inhibiting fibroblast proliferation and collagen deposition.

Extracellular vesicles derived from different sources play various roles in diabetic retinopathy.

Extracellular vesicles (EVs) are present in almost all biological fluids and secreted by almost all cell types. A growing number of studies have revealed the potential roles of EVs in the diagnosis and treatment of the diabetic retinopathy (DR). Changes in the quantity and content of EVs may serve as biomarkers of cause or consequence of pathological status of DR, such as inflammation, neovascularization and epithelial-mesenchymal transition. In addition, as natural, safe and efficient drug carrier, EVs have been reported to play important roles in intercellular communication by acting for essential cell-specific information to target cells. In this review, we summarize the roles of EVs, secreted by various types of cells and participated in various biological processes, in the pathogenesis, diagnosis, and treatment of DR.

Phase transitions in a three-dimensional Ising model with cluster weight studied by Monte Carlo simulations.

The loop model is an important model of statistical mechanics and has been extensively studied in two-dimensional lattices. However, it is still difficult to simulate the loop model directly in three-dimensional lattices, especially in lattices with coordination numbers larger than 3. In this paper, a cluster weight Ising model is proposed by introducing an additional cluster weight n in the partition function of the traditional Ising model. This model is equivalent to the loop model on the two-dimensional lattice, but on the three-dimensional lattice, it is still not very clear whether or not these models have the same universality. By using a Monte Carlo method with cluster updates and color assignment, we obtain the global phase diagram containing the paramagnetic and ferromagnetic phases. The phase transition between the two phases is second order at 1≤n

Association Between Oral Microbiota and Human Brain Glioma Grade: A Case-Control Study.

Gliomas are the most prevalent form of primary malignant brain tumor, which currently have no effective treatments. Evidence from human studies has indicated that oral microbiota is closely related to cancers; however, whether oral microbiota plays a role in glioma malignancy remains unclear. The present study aimed to investigate the association between oral microbiota and grade of glioma and examine the relationship between malignancy-related oral microbial features and the isocitrate dehydrogenase 1 (IDH1) mutation in glioma. High-grade glioma (HGG; n=23) patients, low-grade glioma (LGG; n=12) patients, and healthy control (HCs; n=24) participants were recruited for this case-control study. Saliva samples were collected and analyzed for 16S ribosomal RNA (rRNA) sequencing. We found that the shift in oral microbiota ß-diversity was associated with high-grade glioma (p=0.01). The phylum Patescibacteria was inversely associated with glioma grade (LGG and HC: p=0.035; HGG and HC: p<0.01). The genera Capnocytophaga (LGG and HC: p=0.043; HGG and HC: p<0.01) and Leptotrichia (LGG and HC: p=0.044; HGG and HC: p<0.01) were inversely associated with glioma grades. The genera Bergeyella and Capnocytophaga were significantly more positively correlated with the IDH1 mutation in gliomas when compared with the IDH1-wild-type group. We further identified five oral microbial features (Capnocytophaga Porphyromonas, Haemophilus, Leptotrichia, and TM7x) that accurately discriminated HGG from LGG (area under the curve [AUC]: 0.63, 95% confidence interval [CI]: 0.44-0.83) and HCs (AUC: 0.79, 95% CI: 0.68-0.92). The functional prediction analysis of oral bacterial communities showed that genes involved in cell adhesion molecules (p<0.001), extracellular matrix molecule-receptor interaction (p<0.001), focal adhesion (p<0.001), and regulation of actin cytoskeleton (p<0.001) were associated with glioma grades, and some microbial gene functions involving lipid metabolism and the adenosine 5'-monophosphate-activated protein kinase signaling pathway were significantly more enriched in IDH1 mutant gliomas than compared with the IDH1-wild-type gliomas. In conclusion, our work revealed oral microbiota features and gene functions that were associated with glioma malignancy and the IDH1 mutation in glioma.

A DNA Aptameric Ligand of Human Transferrin Receptor Generated by Cell-SELEX.

General cancer-targeted ligands that can deliver drugs to cells have been given considerable attention. In this paper, a high-affinity DNA aptamer (HG1) generally binding to human tumor cells was evolved by cell-SELEX, and was further optimized to have 35 deoxynucleotides (HG1-9). Aptamer HG1-9 could be taken up by live cells, and its target protein on a cell was identified to be human transferrin receptor (TfR). As a man-made ligand of TfR, aptamer HG1-9 was demonstrated to bind at the same site of human TfR as transferrin with comparable binding affinity, and was proved to cross the epithelium barrier through transferrin receptor-mediated transcytosis. These results suggest that aptamer HG1-9 holds potential as a promising ligand to develop general cancer-targeted diagnostics and therapeutics.

Identification of connexin43 in diabetic retinopathy and its downregulation by O-GlcNAcylation to inhibit the activation of glial cells.

BACKGROUND: Despite advances in the treatments of diabetic complications, proliferative diabetic retinopathy (PDR) still remains a major cause leading to visual loss, mainly because of the lack of pathological mechanisms and complicated protein expressions in vivo. Current study aimed to investigate the patterns of connexin43 (Cx43) changes and the possible interactions with O-GlcNAcylation in DR. METHODS: Clinical samples of vitreous and fibrovascular membranes were acquired from PDR patients during pars plana vitrectomy. Brown Norway rats were used to build diabetic animal models; to investigate the effects of O-GlcNAcylation on Cx43 expressions, total retinal O-GlcNAcylation was changed by intravitreal injections. Levels of protein expressions were examined by immunofluorescence staining and western blot. RESULTS: Our results revealed increased Cx43 expressions in a vessel-shape pattern followed by the distribution of glial fibrillary acidic protein (GFAP) in diabetic fibrovascular membranes. Similarly, Cx43 and GFAP expressions were elevated in PDR vitreous and diabetic animal retinas. Retinal O-GlcNAcylation was effectively regulated by intravitreal injections, and the increase of Cx43 and GFAP was significantly suppressed by O-GlcNAcylation inhibition under hyperglycemia conditions. CONCLUSIONS: We systemically proved the changes of Cx43 with different retinal cells, and reported the effective methods to regulate retinal O-GlcNAcylation by intravitreal injections, and clearly illustrated the downregulated effects of O-GlcNAcylation inhibition on Cx43 and GFAP expressions. GENERAL SIGNIFICANCE: Targeting connexin43 in glial cells reveals a novel mechanism to understand the formation of diabetic fibrovascular membranes and offers a potential therapeutic strategy to interfere the development of PDR.

Macular Vascular Density Changes following Cataract Surgery in Diabetic Patients: An Optical Coherence Tomography Angiography Study.

PURPOSE: Cataracts and diabetes very commonly coexist. The aim of the present study was to quantify the effect of uncomplicated phacoemulsification on retinal microvasculature in diabetic patients by using optical coherence tomography angiography (OCTA). METHODS: A prospective observational study of diabetic and nondiabetic patients at baseline and 1 day, 1 week, 1 month, and 3 months after cataract surgery was performed by using OCTA. We measured the macular thickness (MT), superficial capillary plexus (SCP), deep capillary plexuses (DCP), and foveal avascular zone (FAZ) in the 3 × 3 mm macular images. RESULTS: A total of 32 eyes of 32 type 2 diabetic patients and 40 eyes of 40 nondiabetic patients were assessed. There was a significant increase in MT at 1 month and 3 months after surgery in both groups (all P < 0.05), but there was no significant difference between the two groups (P=0.217). At 3 months postoperatively, the SCP level in the diabetic group was significantly higher than that at baseline (P < 0.05). The MT and SCP were negatively correlated with logMAR best-corrected visual acuity (BCVA), while the FAZ area and perimeter were positively correlated with logMAR BCVA in the diabetic group. CONCLUSIONS: Our study demonstrated that phacoemulsification can increase macular thickness in both diabetic and nondiabetic patients and increase SCP in diabetic patients within 3 months after surgery. Whether these changes persist for a longer period still needs to be investigated.

Iguratimod promotes transformation of mononuclear macrophages in elderly patients with rheumatoid arthritis by nuclear factor-κB pathway.

BACKGROUND: The role of macrophages in rheumatoid arthritis (RA) and its mechanism have attracted much attention in RA pathogenesis. Macrophages accumulate in the synoviums of RA, and the proportion of M1 type pro-inflammatory macrophages is higher than that of M2 type anti-inflammatory macrophages, leading to the secretion of inflammatory molecules and the aggravation of inflammatory reaction, which has made macrophages a potential target of RA drugs. Iguratimod is a kind of cyclo-oxygenase-2 inhibitor that affects macrophage polarity. It is speculated that its anti-inflammatory and anti-rheumatic effects may be related to the regulation of macrophage M1/M2 ratio. AIM: To investigate the effects of Iguratimod on the polarity of mononuclear macrophages in elderly patients with RA. METHODS: Elderly patients with RA and joint effusion were selected, including 10 men and 25 women, with an average age of 66.37 ± 4.42 years. Patients were treated with oral administration of 25 mg Iguratimod (Iremod, State Food and Drug Administration Approval No. H20110084) twice daily for 12 wk. Disease Activity Score 28 and Health Assessment Questionnaire score were collected according to the disease severity before and after treatment. Venous blood and joint effusion fluid were collected, mononuclear macrophages were extracted and expression of cell surface markers CD86, CD64, CD163, and CD206 was analyzed by flow cytometry. The concentration of inflammatory factors interleukin (IL)-6, IL-1ß, transforming growth factor-ß, and IL-4 in the joint effusion fluid was analyzed by enzyme-linked immunosorbent assay. Expression of mononuclear cells inhibitor of nuclear factor-κB (IκB) and phosphorylated IκB in peripheral blood was analyzed by western blotting. RESULTS: Disease Activity Score 28 score and Health Assessment Questionnaire score of patients treated with Iguratimod decreased significantly. The percentage of cell surface markers CD86 and CD64 decreased significantly, and the percentage of CD163 and CD206 increased significantly (P < 0.05). The inflammatory factors IL-6 and IL-1ß decreased significantly, and transforming growth factor-ß and IL-4 increased significantly. Western blot analysis showed that mononuclear cell inhibitor of nuclear factor-κB in peripheral blood was significantly increased after treatment, and its phosphorylation level was significantly decreased (P < 0.05). CONCLUSION: Iguratimod can promote the transformation of mononuclear macrophages from M1 to M2 in elderly patients with RA by inhibiting the nuclear factor-κB pathway, thus improving symptoms of RA.