OBJECTIVE: To prepare vitamin E polyethylene glycol 1000 succinate (TPGS)-modified insulin-loaded liposomes (T-LPs/INS) and evaluate its safety, corneal permeability, ocular surface retention and pharmacokinetics in rabbit eyes. METHODS: The safety of the preparation was investigated in human corneal endothelial cells (HCECs) using CCK8 assay and live/dead cell staining. In the ocular surface retention study, 6 rabbits were randomized into 2 equal groups for application of fluorescein sodium dilution or T-LPs/INS labeled with fluorescein in both eyes, which were photographed under cobalt blue light at different time points. In the cornea penetration test, another 6 rabbits divided into 2 groups for application of Nile red diluent or T-LPs/INS labeled with Nile red in both eyes, after which the corneas were harvested for microscopic observation. In the pharmacokinetic study, 2 groups of rabbits (n=24) were treated with eye drops of T-LPs/INS or insulin, and the aqueous humor and cornea were collected at different time points for measurement of insulin concentrations using enzyme linked immunosorbent assay. DAS2 software was used to analyze the pharmacokinetic parameters. RESULTS: The prepared T-LPs/INS showed good safety in cultured HCECs. Corneal permeability assay and fluorescence tracer ocular surface retention assay demonstrated a significantly higher corneal permeability of T-LPs/INS with a prolonged drug residence in the cornea. In the pharmacokinetic study, insulin concentrations in the cornea at 6, 15, 45, 60, and 120 min (P < 0.01) and in the aqueous humor at 15, 45, 60, and 120 min after dosing were significantly higher in T-LPs/INS group. The changes in insulin concentrations in the cornea and aqueous humor were consistent with a two-compartment model in T-LPs/INS group and with the one-compartment model in the insulin group. CONCLUSION The prepared T-LPs/INS shows an improved corneal permeability, ocular surface retention capacity and eye tissue concentration of insulin in rabbits.
Humans ; Animals ; Rabbits ; Insulin ; Liposomes ; Endothelial Cells ; Lipopolysaccharides ; Vitamin E ; Cornea ; Fluorescein

OBJECTIVES: To compare the clinical efficacy and safety of acupuncture and sodium hyaluronate eye drop in the treatment of aqueous deficiency dry eye. METHODS: A total of 60 patients (120 eyes) with aqueous deficiency dry eye were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases, 1 case dropped out). In the control group, sodium hyaluronate eye drop were used, one drop at a time, 4 times a day, for 14 consecutive days. In the observation group, acupuncture was applied at bilateral Shangjingming (Extra), Cuanzhu (BL 2), Sizhukong (TE 23), Taiyang (EX-HN 5), and Tongziliao (GB 1) , once a day, treatment for 6 days with the interval of 1 day was required, for 14 consecutive days. The tear meniscus height (TMH), Schirmer Ⅰ test (SⅠT), ocular surface disease index (OSDI) score, non-invasive tear break-up time (NIBUT), and corneal fluorescein sodium staining (FLS) score were compared between the two groups before and after treatment, and the safety of the treatment of the two groups was observed. RESULTS: Compared with those before treatment, after treatment, TMH, SⅠT and NIBUT were increased (P<0.01, P<0.05), and FLS scores were decreased (P<0.01) in the two groups; the score of OSDI was reduced (P<0.01) in the observation group. After treatment, in the observation group, TMH and SⅠT were higher than those in the control group (P<0.01), and the score of OSDI was lower than that in the control group (P<0.01). No adverse reactions and adverse events were observed in the two groups. CONCLUSIONS Acupuncture and sodium hyaluronate eye drop can both effectively treat aqueous deficiency dry eye, acupuncture has obvious advantages in improving TMH and basic tear secretion, and reducing the subjective symptoms of patients. Acupuncture for dry eye is safe.
Humans ; Hyaluronic Acid ; Acupuncture Therapy ; Dry Eye Syndromes/therapy* ; Eye ; Tears ; Ophthalmic Solutions ; Fluorescein

Background: Contrast-induced nephropathy (CIN) is a complication that occurs in patients undergoing an imaging procedure with intravenous injection of contrast media, most notably iodinated dyes. Fluorescein angiography is a diagnostic procedure performed by ophthalmologists to determine abnormalities in retinal blood vessels. It uses sodium fluorescein, an organic dye, to capture and visualize these blood vessels. There have been conflicting data and practices on how to approach the procedure especially in patients with renal insufficiency. Objective: To determine the risk of CIN among patients undergoing fluorescein angiography. Methods: We searched PubMed, HerdIn, Cochrane Library, and Google Scholar, for published articles on the topic. Other sources were searched for unpublished data or ongoing clinical trials. All research articles pertaining to fluorescein angiography and its effect on renal function with serum creatinine monitoring were included. Two independent authors separately screened records, assessed full texts, and extracted data. We used RevMan computer software to analyze data from the included studies. The primary outcome was the risk of CIN among patients undergoing fluorescein angiography based on the differences on serum creatinine levels and estimated glomerular filtration rates pre- and post-angiography, while the secondary outcome included risk factors for CIN. Results: A total of 6 studies were included in the meta-analysis. Four studies had poor quality as assessed using the Newcastle-Ottawa Scale. One study was deemed to have good quality. Data analysis showed that hemoglobin (p = 0.002) and albumin (p < 0.001) levels may be associated with CIN using sodium fluorescein but were not independent risk factors for CIN (multivariable logistic regression, p = 0.648 and p = 0.069, respectively); while sex, diabetes mellitus and chronic kidney disease were not significantly associated. As a primary outcome, only 6.8% of included patients had CIN with serum creatinine levels post-exposure showed significant differences from baseline values (mean difference 0.05; 95% CI 0.02, 0.07; I2 = 49%), but translating it to eGFR yielded non-significant differences (mean difference -0.37; 95% CI -2.33, 1.59; I2 = 0%). Conclusion Among patients undergoing fluorescein angiography, sodium fluorescein does not pose an increased risk for CIN.
fluorescein angiography ; renal function

Objective The main objective of this study is to determine the agreement between the clinical staging of diabetic retinopathy (DR) with fluorescein angiography (FA) staging in an actual clinic.
Diabetic Retinopathy ; Fluorescein Angiography ; Ophthalmoscopy ; Diabetes Mellitus

OBJECTIVE: To explore the effect and mechanism of action of bufalin in triple-negative breast cancer (TNBC) drug-resistant cell lines. METHODS: The normal human mammary epithelial cell line, TNBC cell line, TNBC adriamycin-resistant cell line, and TNBC docetaxel-resistant cell line were treated with different doses of bufalin (0-1,000 nmol/L) at different time points (0-72 h). Propidium iodide staining, AV-FITC/PI double staining, Hoechst 33342/PI double staining and transmission electron microscopy (TEM) were used to evaluate the death patterns of the cell lines. RESULTS: Bufalin killed the TNBC cell line and its drug-resistant cell lines in a dose/time-dependent manner (all P<0.01). After treatment with bufalin for 24 h, the adriamycin-resistant cell line showed a co-existing pattern of necroptosis and apoptosis. However, at 48 h, necroptosis was the main manifestation. After treatment with bufalin, the expressions of tumor necrosis factor α, phospho-tumor necrosis factor receptor 1, phospho-receptor interacting protein 1 and c-caspase 3 increased (all P<0.01), the killing effect of bufalin could be mostly inhibited by NEC-1, and by z-VAD-fmk (both P<0.01). Besides, the intracellular reactive oxygen species (ROS) levels increased considerably (P<0.01), the antioxidant N-acetyl cysteine or Nec-1 could inhibit the increase of ROS level and the killing effect of bufalin (all P<0.01). The adriamycin-resistant cell line exhibited necroptosis characteristic after 48 h of bufalin treatment under TEM. CONCLUSIONS Bufalin could induce necroptosis through RIP1/ROS-mediated pathway to kill the drug-resistant TNBC cell lines. This finding provides critical experimental data and theoretical basis for the clinical application of bufalin to overcome the difficulties in the treatment of TNBC.
Antioxidants/pharmacology* ; Apoptosis ; Bufanolides ; Caspase 3/metabolism* ; Cell Line ; Cell Line, Tumor ; Cysteine/pharmacology* ; Docetaxel/pharmacology* ; Doxorubicin/pharmacology* ; Fluorescein-5-isothiocyanate/pharmacology* ; Humans ; Necroptosis ; Propidium/pharmacology* ; Reactive Oxygen Species/metabolism* ; Receptors, Tumor Necrosis Factor ; Triple Negative Breast Neoplasms/drug therapy* ; Tumor Necrosis Factor-alpha/pharmacology*

OBJECTIVES: Central serous chorioretinopathy (CSC) is generally a common fundus disease in young and middle-aged Asian men. Acute and chronic CSC can lead to different degrees of injury to the retinal blood flow. This study aims to observe and compare the blood flow density in different retinal capillary layers in patients with acute and chronic CSC using optical coherence tomography angiography (OCTA) technology. METHODS: Twelve patients with acute CSC and 8 patients with chronic CSC including 12 eyes with acute CSC (acute CSC eye group), 11 eyes with chronic CSC (chronic CSC eye group), and 17 normal eyes (normal eye group) were enrolled in this study. All patients underwent 3 mm×3 mm, 6 mm×6 mm macular OCTA scanning. The retinal microvascu-lature was divided into superficial vascular complexes (SVC), intermediate capillary plexuses (ICP), and deep capillary plexuses (DCP) using the projection resolved-OCTA algorithm. Inner retina includes SVC, ICP, and DCP. The vessel density in each retinal layer and the inner retina were calculated and compared. RESULTS: Macular OCTA scanning of 3 mm×3 mm showed that there was no significant difference in blood flow density of SVC and ICP among the 3 groups (both P>0.05); blood flow density of DCP and inner retina in the chronic CSC eye group was significantly lower than that in the acute CSC eye group and the normal eye group (all P<0.05); there was no significant difference in retinal blood flow density of different layer between the acute CSC eye group and the normal eye group (all P>0.05). Macular OCTA scanning of 6 mm×6 mm showed that inner retinal blood flow density of the chronic CSC eye group was significantly lower than that of the acute CSC eye group and the normal eye group (both P<0.05); there was no significant difference in blood flow density of SVC among the 3 groups (P>0.05). CONCLUSIONS The vessel density of DCP and inner retina in the eyes with chronic CSC are significantly reduced, which may result in impaired visual function. Therefore, we recommend that patients with acute CSC should be properly treated to avoid progressing into chronic CSC.
Central Serous Chorioretinopathy/diagnostic imaging* ; Fluorescein Angiography/methods* ; Humans ; Male ; Microvessels/diagnostic imaging* ; Middle Aged ; Retina ; Tomography, Optical Coherence/methods*

OBJECTIVE: To evaluate the value of fundus autofluorescence (FAF) imaging combined with spectral domain optical coherence tomography (SD-OCT) in diagnosis, prognostic assessment and follow-up observation of acute Vogt-KoyanagiHarada (VKH) disease. METHODS: Clinical data were collected from 12 patients (23 eyes) with acute VKH disease treated in our hospital from May, 2018 to November, 2019, including detailed medical history, best corrected visual acuity (BCVA), and results of slit lamp biomicroscopy, fundus photography, SD-OCT, fundus fluorescein angiography (FFA) and FAF imaging.SDOCT and FAF imaging were repeated after a course of treatment and in follow-up examination, and the results were compared with those at the time of admission. RESULTS: VKH disease involved both eyes in 11 patients (91.7%).Fundus photography showed optic disc edema in 16 eyes (69.6%), and multiple retinal neuroepithelial detachment was detected by SD-OCT in all the involved eyes (100%).IN all the eyes, FFA revealed small and dense fluorescein leakage in the early stage and fluorescein accumulation in advanced stages of VHK disease to form multiple dye pooling in the areas of serous detachment.Hyperauto fluorescence was a common finding in FAF imaging (100%), and the area involved was consistent with that of fluorescein accumulation shown by FAF imaging.Ten eyes (43.5%) showed patches of relative hypoautofluorescence in the hyperauto fl uorescence areas, and granular hyperauto fl uorescence was found in the lesions in 4 eyes (17.4%).During the remission period of VKH disease, FAF imaging showed normal finding in 8 eyes (34.8%) and reduced areas (by 55.2%) and intensity (by 46.5%) of hyperautofluorescence in 9 eyes (39.1%).In 6 eyes (26.1%), only a few hyperautofluorescent spots scattered in the macula were observed.SD-OCT demonstrated significantly reduced (by 69.5% on average) or even disappearance of subretinal fluid in the eyes.The fluorescence intensity in FAF imaging showed a significant positive correlation with the volume of subretinal fluid detected by SD-OCT ( CONCLUSIONS The combination of fluorescein angiography, FAF imaging and SD-OCT can significantly improve the diagnostic accuracy of VKH disease.FAF imaging combined with SD-OCT provides an effective and noninvasive modality for evaluation of remission and monitoring the changes in VKH disease.
Acute Disease ; Fluorescein Angiography ; Follow-Up Studies ; Humans ; Retinal Detachment/diagnostic imaging* ; Tomography, Optical Coherence ; Uveomeningoencephalitic Syndrome/diagnostic imaging*

PURPOSE: The effect of air pollution-related particulate matter (PM) on epithelial barrier function and tight junction (TJ) expression in human nasal mucosa has not been studied to date. This study therefore aimed to assess the direct impact of PM with an aerodynamic diameter less than 2.5 μm (PM2.5) on the barrier function and TJ molecular expression of human nasal epithelial cells. METHODS: Air-liquid interface cultures were established with epithelial cells derived from noninflammatory nasal mucosal tissue collected from patients undergoing paranasal sinus surgery. Confluent cultures were exposed to 50 or 100 µg/mL PM2.5 for up to 72 hours, and assessed for 1) epithelial barrier integrity as measured by transepithelial resistance (TER) and permeability of fluorescein isothiocyanate (FITC) 4 kDa; 2) expression of TJs using real-time quantitative polymerase chain reaction and immunofluorescence staining, and 3) proinflammatory cytokines by luminometric bead array or enzyme-linked immunosorbent assay. RESULTS: Compared to control medium, 50 and/or 100 µg/mL PM2.5-treatment 1) significantly decreased TER and increased FITC permeability, which could not be restored by budesonide pretreatment; 2) significantly decreased the expression of claudin-1 messenger RNA, claudin-1, occludin and ZO-1 protein; and 3) significantly increased production of the cytokines interleukin-8, TIMP metallopeptidase inhibitor 1 and thymic stromal lymphopoietin. CONCLUSIONS: Exposure to PM2.5 may lead to loss of barrier function in human nasal epithelium through decreased expression of TJ proteins and increased release of proinflammatory cytokines. These results suggest an important mechanism of susceptibility to rhinitis and rhinosinusitis in highly PM2.5-polluted areas.
Asthma ; Budesonide ; Claudin-1 ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; Fluorescein ; Fluorescein-5-isothiocyanate ; Fluorescent Antibody Technique ; Humans ; Interleukin-8 ; Mucous Membrane ; Nasal Mucosa ; Occludin ; Particulate Matter ; Permeability ; Polymerase Chain Reaction ; Rhinitis ; RNA, Messenger ; Tight Junctions

OBJECTIVE: To determine the incidence of contrast-induced nephropathy (CIN) among patients undergoing fundus fluorescein angiography (FFA) METHODS: One hundred fifty-nine (159) patients from the Ophthalmology out-patient department were enrolled in this prospective, observational study. Serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) were measured within 7 days before and 48 to 72 hours after FFA. Subjects were stratified into low-, intermediate-, and high-risk groups for developing CIN according to baseline eGFR. CIN was defined by an increase in SCr by more than 25% or by 0.5 mg/dL within 72 hours of intravascular administration of contrast media. The incidence of CIN, changes in SCr levels, and changes in eGFR were analyzed. RESULTS: Of the 144 subjects who completed the study, 106 (73.6%) were females, 105 (72.9 %) were diabetics, and 57 (39.6%) had elevated baseline SCr. Four (4 or 2.8%) patients developed CIN after FFA, all of whom had normal baseline SCr and were stratified as low-risks. Overall, there were no significant changes in the means of SCr (1.18 ± 0.56 vs 1.16 ± 0.52, p = 0.13) and eGFR (64.53 ± 26.05 vs 64.94 ± 24.88, p = 0.64) before and after FFA. In the low-risk group, the means of SCr and eGFR remained unchanged after FFA (p = 0.06 and p = 0.15, respectively). In the intermediate-risk group, no significant change was appreciated in SCr levels (p = 0.07) however a significant improvement in eGFR (p = 0.006) was seen. Interestingly, a significant decrease in SCr levels (p = 0.004) as well as a significant improvement in eGFR (p = 0.02) was noted after FFA in the high-risk group. CONCLUSION: The incidence of CIN among patients undergoing FFA in our cohort was 2.8%. There was no prolonged or serious worsening of renal function based on SCr and eGFR before and after FFA overall, and among low-, moderate-, and high-risk groups.
Creatinine ; Glomerular Filtration Rate ; Contrast Media ; Incidence ; Fluorescein Angiography ; Acute Kidney Injury ; Drug-Related Side Effects and Adverse Reactions

The aim of this paper was to investigate the preventive effects of Keluoxin Capsules(KLX) on diabetic retinopathy in db/db mice. One hundred male db/db diabetic mice(45-55 g, 8 weeks) were randomly divided into 5 groups(model, KLX low dose, KLX middle dose, KLX high dose, Dobesilate) and 20 male C57 BL/KsJdb~(+/+) were taken as control group. Body weight and fasting blood-glucose were detected every week. Mice were administrated with saline(control and model group), KLX(780, 1 560, 3 120 mg·kg~(-1)·d~(-1), ig), Dobesilate(195 mg·kg~(-1)·d~(-1), ig) for 20 weeks, respectively. At the end of the administration, optical coherence tomography, fundus fluorescein angiography and electroretinogram of the retina were measured. The eyeball was extirpated and retina was isolated to make paraffin section, followed by HE staining and glial fibrillary acidic protein(GFAP) immunohistochemistry. The results indicated that KLX has no obvious effect on body weight and fasting blood level in db/db mice. However, KLX could significantly regulate the thickness of retinal ganglion layer and inner plexiform layer. KLX was able to remarkably reduce the quantity of diabetic microvessel. Meanwhile, KLX could notably improve retinal function. Moreover, KLX could observably modulate the cell arrangement and edema in each layer. There was no markable difference in retina according to the immunochemistry assay. In the present study, KLX exert marked preventive effects on diabetic retinopathy in db/db mice, which provided an experimental evidence for clinical use.
Animals ; Capsules ; Diabetes Mellitus, Experimental ; Diabetic Retinopathy ; drug therapy ; Fluorescein Angiography ; Hypoglycemic Agents ; pharmacology ; Male ; Mice ; Random Allocation ; Retina ; drug effects