1.Interleukin-8 antagonist down regulates the adhesion and migration of retinal vascular endothelial cells by inhibiting the production of reactive oxygen species
Linni WANG ; Jingjing CAO ; Dongjun XING ; Rongguo YU ; Liying HU ; Yang YANG ; Chang LI ; Zhiqing LI ; Hui LI ; Yaru HONG ; Lijie DONG
Chinese Journal of Ocular Fundus Diseases 2023;39(11):913-917
Objective:To observe the effect of interleukin-8 (IL-8) on the adhesion and migration of retinal vascular endothelial cells (RCEC).Methods:A cell experiment. Human RCEC (hRCEC) was divided into normal control group (N group), advanced glycation end product (AGE) treatment group (AGE group), and AGE-induced combined IL-8 antagonist SB225002 treatment group (AGE+SB group). The effect of AGE on IL-8 expression in hRCEC was observed by Western blot. The effect of SB225002 on hRCEC migration was observed by cell scratch assay. The effects of SB225002 on leukocyte adhesion and reactive oxygen species (ROS) on hRCEC were detected by flow cytometry. Student- t test was performed between the two groups. Oneway analysis of variance was performed among the three groups. Results:Compared with group N, the expression level of IL-8 in cells of AGE group was significantly increased, with statistical significance ( t=25.661, P<0.001). Compared with N group and AGE+SB group, cell mobility in AGE group was significantly increased ( F=29.776), leukocyte adhesion number was significantly increased ( F=38.159, 38.556), ROS expression level was significantly increased ( F=22.336), and the differences were statistically significant ( P<0.05). Conclusion:IL-8 antagonist SB225002 may down-regulate hRCEC adhesion and migration by inhibiting ROS expression.
2.Comprehensive analysis of pathogenic genes and clinical phenotypes in patients with Leber congenital amuarosis
Dongjun XING ; Zhiqing LI ; Rongguo YU ; Linni WANG ; Liying HU ; Yang YANG ; Chang LI ; Xiaorong LI
Chinese Journal of Ocular Fundus Diseases 2022;38(8):663-667
Objective:To observe clinical phenotypes and analyze the pathogenic genes of Leber congenital amaurosis (LCA).Methods:A retrospective clinical study. From 2019 to 2020, 2 patients diagnosed with LCA by genetic testing in Tianjin Medical University Eye Hospital and their 6 unaffected family members were enrolled in the study. Two patients were from 2 unrelated families, both were probands. The patient's medical history was inquired in detail, slit lamp microscopy, ultra-widefield fundus photography, autofluorescence, and flash visual evoked potential (F-VEP) were performed. Peripheral vein blood (3-5 ml) was collected and genomic DNA was extracted from all study subjects. A total of 381 pathogetic genes associated with inherited retinal diseases, were selected by targeted exome sequencing capture strategy. Sanger sequencing was used to verify suspected pathogenic mutations. Candidate pathogenic mutations were identified after bioinformatics analysis. Sanger sequencing, real-time quantitative polymerase chain reaction and family co-identification were used to confirm the final mutations.Results:Two patients were male, aged 3 and 27 years. One case had vision loss in both eyes, accompanied by nystagmus and acupressure eye sign since childhood. The clinical hallmark of the proband (F1-Ⅱ-3) in F1 includes clearly boundary of optic disc, normal retinal blood vessels and macular fovea. The implied period of the maximum forward wave in both eyes of F-VEP was roughly normal, and its amplitude decreased significantly. The phenotype of the proband (F2-Ⅱ-1) in F2 includes optic nerve head pallor, bone-spicule intraretinal pigmentation, "gold-foil maculopathy" , retina patchy hypo-autofluorescence in both eyes. There was no abnormal phenotype in the eyes of the family members. According to the genetic diagnosis, the proband (F1-Ⅱ-3) carried the GUCY2D gene c.835G>A (p.D279N) (M1) and exon 9-19 deletion (M2) compound heterozygous mutations, in which M1 was derived from healthy mother and M2 was derived from healthy father. The proband (F2-Ⅱ-1) carried CRB1 gene c.1576C>T(R526X) (M3) and c.1522T>C (C508R) (M4) compound heterozygous mutations, in which M3 from the healthy father, M4 from the healthy mother. M2 and M4 were novel mutations. Conclusion:GUCY2D gene mutations lead to LCA1 type in the F1 family, CRB1 gene mutations lead to LCA8 type in the F2 family; there are significant different phenotypes caused by different pathogenic genes.
3.Association between single nucleotide polymorphism and response to anti vascular endothelial growth factor therapy in patients with wet age-related macular degeneration
Xinxuan YIN ; Dongjun XING ; Tingli WANG ; Rongguo YU ; Linni WANG ; Liying HU ; Xue GONG ; Lu CHEN ; Zhiqing LI
Chinese Journal of Ocular Fundus Diseases 2021;37(9):693-701
Objective:To observe the relationship between the response to anti-vascular endothelial growth factor (VEGF) drug treatment and single nucleotide polymorphism (SNP) genotype in patients with wet age-related macular degeneration (wAMD).Methods:A retrospective clinical study. From August 2019 to September 2020, 103 eyes of 103 wAMD patients diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 59 males (57.28%, 59/103) and 44 females (42.72%, 44/103); the average age was 68.74±7.74 years. The standard logarithmic visual acuity chart was used to detect the Best Corrected Visual Acuity of the affected eye and converted to the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. Optical coherence tomography was used to detect the central retinal thickness (CRT) of the affected eye. At the same time, the patient's high-density lipoprotein cholesterol (HDL-C) was tested. All eyes were treated with intravitreal injection of anti-VEGF drugs once a month for 3 months. Before the initial treatment, peripheral venous blood from the patient were collected. Interleukin-8 ( IL-8), complement C3 gene ( C3), complement factor H ( CFH), liver lipase ( LIPC), cholesterol ester transfer protein ( CETP), ATP binding cassette subfamily a member 1 ( ABCA1), lipoprotein lipase ( LPL), fatty acid desaturation gene cluster ( FADS1) SNP. According to gene frequency, genotypes are divided into wild type and mutant type were detected. Qualitative data such as the frequency difference of the genotype distribution in the clinical phenotype and the Hardy-Weinberg equilibrium of the genotype distribution were compared with the Chi-square test or Fisher's exact test. Results:There were fewer CRT responders in IL-8 rs4073 mutant (TA+AA) patients than wild-type (TT) [odds ratio ( OR)=0.310, 95% confidence interval ( CI) 0.106-0.910, P<0.05). Among them, after the drug stratification test, the proportion of patients with IL-8 rs4073 locus TT genotype in the conbercept treatment group was less CRT non-responders ( OR=0.179, 95% CI=0.034-0.960, P=0.033). Patients with LIPC rs2043085 mutant (CT+TT) with BCVA increased ≥0.2 logMAR are more likely than wild-type (CC) ( OR=3.031, 95% CI 1.036-8.867, P<0.05); HDL-C level was significantly lower Compared with wild type (CC), the difference was statistically significant ( t=2.448, P=0.016). There was no significant difference in logMAR BCVA and CRT between IL-8 rs4073, LIPC rs2043085 mutant and wild-type patients before treatment ( IL-8 rs4073: Z=-0.198, -1.651; P=0.843, 0.099; LIPC rs2043085: Z=-0.532, -0.152; P=0.595, 0.879). C3 rs 225066, CFH rs800292, CETP rs708272, ABCA1 rs1883025, FADS1 rs174547, LPL rs12678919 have no correlation with anti-VEGF drug treatment response. Conclusions:Patients with wAMD are treated with anti-VEGF drugs. Those with IL-8 rs4073 locus A genotype may be less responsive to CRT. LIPC rs2043085 locus T genotypes may be relatively more responsive to BCVA.
4.Automatic Detection and Classification of Rib Fractures on Thoracic CT Using Convolutional Neural Network: Accuracy and Feasibility
Qing-Qing ZHOU ; Jiashuo WANG ; Wen TANG ; Zhang-Chun HU ; Zi-Yi XIA ; Xue-Song LI ; Rongguo ZHANG ; Xindao YIN ; Bing ZHANG ; Hong ZHANG
Korean Journal of Radiology 2020;21(7):869-879
Objective:
To evaluate the performance of a convolutional neural network (CNN) model that can automatically detect and classify rib fractures, and output structured reports from computed tomography (CT) images.
Materials and Methods:
This study included 1079 patients (median age, 55 years; men, 718) from three hospitals, between January 2011 and January 2019, who were divided into a monocentric training set (n = 876; median age, 55 years; men, 582), five multicenter/multiparameter validation sets (n = 173; median age, 59 years; men, 118) with different slice thicknesses and image pixels, and a normal control set (n = 30; median age, 53 years; men, 18). Three classifications (fresh, healing, and old fracture) combined with fracture location (corresponding CT layers) were detected automatically and delivered in a structured report. Precision, recall, and F1-score were selected as metrics to measure the optimum CNN model. Detection/diagnosis time, precision, and sensitivity were employed to compare the diagnostic efficiency of the structured report and that of experienced radiologists.
Results:
A total of 25054 annotations (fresh fracture, 10089; healing fracture, 10922; old fracture, 4043) were labelled for training (18584) and validation (6470). The detection efficiency was higher for fresh fractures and healing fractures than for old fractures (F1-scores, 0.849, 0.856, 0.770, respectively, p = 0.023 for each), and the robustness of the model was good in the five multicenter/multiparameter validation sets (all mean F1-scores > 0.8 except validation set 5 [512 x 512 pixels; F1-score = 0.757]). The precision of the five radiologists improved from 80.3% to 91.1%, and the sensitivity increased from 62.4% to 86.3% with artificial intelligence-assisted diagnosis. On average, the diagnosis time of the radiologists was reduced by 73.9 seconds.
Conclusion
Our CNN model for automatic rib fracture detection could assist radiologists in improving diagnostic efficiency, reducing diagnosis time and radiologists’ workload.
5.The effect of macular edema on quantitative analysis of foveal avascular zone in branch retinal vein occlusion eyes
Linni WANG ; Rongguo YU ; Jin YANG ; Liying HU ; Xue GONG ; Lu CHEN ; Zhiqing LI ; Xiaorong LI
Chinese Journal of Ocular Fundus Diseases 2019;35(1):20-24
Objective To observe the effect of different macular edema on the area of foveal avascular zone (FAZ) and its correlation in eyes with branch retinal vein occlusion (BRVO).Methods A total of 72 patients (75 eyes) diagnosed with BRVO were included in the study.There were 40 patients males (42 eyes) and 32 females (33 eyes),with the mean age of (56.00±9.96) years.All the eyes were examined by BCVA,intraocular pressure,slit lamp microscope combined with preset lens,fundus color photography and optical coherence tomography angiography (OCTA).BRVO patients were divided into two groups according to the degree of macular edema:group M300 that was CRT ≥300 μm (38 patients,39 eyes) and group L300 that was CRT<300 μmn (34 patients,36 eyes).The macular angiography scan protocol covered a 3 mm × 3 mm area.The parameters of macular were measured by the built-in measurement software of the system:(1) area of FAZ,perimeter ofFAZ (PERIM),avascular index ofFAZ (AI),vascular density within a width of 300 μm around the FAZ region (FD-300);(2) central retinal thickness (CRT);(3) vascular density (VD):the superficial central fovea vascular density (SFVD),the deep central fovea vascular density (DFVD),the superficial hemi-macular vascular density (SHVD),the deep hemi-macular vascular density (DHVD).Spearman test was used to test the correlation between FAZ area and other parameters in each group.Results The FAZ area in group M300 and L300 were 0.388 ± 0.166 mmn2 and 0.596± 0.512 rmm2,respectively.The results of Spearman test showed that the FAZ area of group M300 was positively correlated with PERIM and AI (r=0.932,0.591;P=0.000,0.000),negatively correlated with SFVD,DFVD and SHVD (r=-0.490,-0.429,-0.339;P=0.002,0.006,0.035).But there was no significant negative correlation between FAZ area and FD-300,CRT,DHVD in group M300 (r=-0.129,-0.053,-0.400;P=0.435,0.749,0.395).The FAZ area in group L300 was positively correlated with PERIM and AI (r=0.887,0.633;P=0.000,0.000),negatively correlated with SFVD,DFVD,SHVD and DHVD (r=-0.413,-0.643,-0.630,-0.370,-0.411;P=0.012,0.000,0.000,0.026,0.013).But there was no significant positive correlation between FAZ area and FD-300 in group L300 (r=0.093,P=0.590).Conclusion FAZ area varies with the degree of macular edema.The degree of macular edema is higher,the FAZ area is smaller.FAZ area is positively correlated with PERIM and AI significantly,and negatively correlated with SFVD,DFVD and SHVD.
6.Study on the quality standard of improvement of Tongluo-Zhujing pills
Yuying HU ; Kangle LI ; Mingjie LI ; Rongguo SHANG ; Hua AI ; Xiaoqin LEI
International Journal of Traditional Chinese Medicine 2018;40(4):350-353
Objective To improve the quality standard of Tongluo-Zhujing pills.Methods We added the identification ofradix notoginseng andtypha orientalisby TLC and determination of the content of wedelolactone by HPLC. The study used Agilent ZORBAX SB-C18 (4.6 mm × 250 mm, 5 μm) column and the velocity of flow manufactured by the proper proportion was 1 ml/min. The detection wavelength was 249 nm . Results The new method could well identify radix notoginsengandtypha orientalis. The calibration curves of wedelolactone was in good linearity over the range of 0.064-0.642 μg (r=0.999 7) and the average recovery was 98.74%(RSD=1.61%).Conclusions The quality standard of Tongluo-Zhujing pills was proved effectively.
7.The difference of macular microvascular features in superficial and deep vascular plexi in patients with branch retinal vein occlusion
Linni WANG ; Rongguo YU ; Jin YANG ; Liying HU ; Xue GONG ; Lu CHEN ; Zhiqing LI ; Xiaorong LI
Chinese Journal of Ocular Fundus Diseases 2018;34(1):13-16
Objective To observe the difference of macular microvascular features in superficial and deep vascular plexi in patients with branch retinal vein occlusion (BRVO).Methods A total of 63 BRVO patients (63 eyes) were enrolled in this study. There were 28 males (28 eyes) and 35 females (35 eyes). The patients aged from 39 to 74 years, with the mean age of (59.76±8.48) years. All eyes were evaluated by optical coherence tomography angiography (OCTA). The macular angiography scan protocol covered a 3 mm×3 mm area. The focus of angiography analysis included superficial vascular plexus and deep vascular plexus. The following vascular morphological parameters were assessed in these two plexi: foveal avascular zone (FAZ) enlargement, capillary non-perfusion (CNP) occurrence, microvascular abnormalities (MA) appearance, and vascular congestion (VC) signs. The FAZ area was measured by the built-in software. The macular microvascular morphology changes in superficial and deep vascular plexi were compared through McNemar test. Results The superficial and deep plexi showed FAZ enlargement in 43 eyes (68.3%) and 50 eyes (79.4%), CNP in 51 eyes (81%) and 50 eyes (79.4%), MA in 62 eyes (98.4%) and 62 eyes (98.4%), VC in 23 eyes (36.5%) and 52 eyes (82.5%), respectively. FAZ area was (0.55±0.37) mm2. There was no difference in CNP (P=1.000) and MA (P=1.000) between superficial and deep plexi. But, there was difference in FAZ enlargement (P=0.039) and VC signs (P<0.001) between superficial and deep plexi.Conclusion Deep vascular plexus showed more FAZ enlargement and VC sign than superficial plexus in BRVO patients.
8.Distribution and antimicrobial resistance of bloodstream pathogens in surgical and medical ICUs
Shurong GONG ; Xinlan HU ; Rongguo YU
Chinese Journal of Infection and Chemotherapy 2018;18(1):68-75
Objective To analyze the distribution and antimicrobial resistance of bloodstream pathogens in surgical intensive care unit (SICU) and medical intensive care unit (MICU) of Fujian Provincial Hospital in the past four and half years for better use of antimicrobial drugs.Methods A retrospective analysis was carried out for the bloodstream pathogens isolated from SICU and MICU patients from January 2012 to June 2016.The clinical data and outcomes of patients were also reviewed.Results A total of 329 strains of isolates were recovered from blood samples in SICU,including gram-negative bacteria (53.5%),gram-positive bacteria (39.2%),and fungi (7.3%);258 strains were collected from MICU,including gram-negative bacteria (57.8%),gram-positive bacteria (36.0%),and fungi (6.2%).A.baumannii,K.pneumonia and E.coli were the top three gram-negative species in both SICU and MICU.The main gram-positive species were coagulase-negative Staphylococcus and Enterococcusfaecium.Overall,386 cases of bloodstream infections were diagnosed,including 226 cases in SICU (202 cases of single bacterial infection and 24 cases of multiple bacterial infection),and 160 cases in MICU (138 cases of single bacterial infection and 22 cases of multiple bacterial infection).A.baumannii isolates showed significantly higher rate of resistance to antibiotics in SICU than in MICU,while the K.pneumoniae and E.coli isolates in MICU showed higher resistance rates to cephalosporins,quinolones,penicillins and carbapenems than the corresponding isolates in SICU.The coagulase negative Staphylococcus and E.faecium isolates in MICU were associated with significantly higher resistance rates to quinolones and tigecycline than those strain in SICU.The bloodstream infections due to K.pneumoniae,E.coli and E.faecium were associated with higher mortality in MICU than in SICU,while the bloodstream infections due to A.baumannii were associated with higher mortality in SICU than in MICU.The total mortality rate of bloodstream infections was higher in MICU than in SICU.Conclusions SICU and MICU share similar profile of main bloodstream pathogens even though the disease spectrum was different between SICU and MICU.All the bloodstream pathogens isolated from MICU patients except A.baumannii showed significantly higher antimicrobial resistance rates than the isolates from SICU.The mortality rate associated with bloodstream infection was also higher in MICU patients than in SICU.
9.The application of ultra-wide field fluorescein angiography in the evaluation of peripheral vascular changes following retinal vein occlusion
Linni WANG ; Rongguo YU ; Jin YANG ; Liying HU ; Xue GONG ; Lu CHEN ; Zhiqing LI ; Xiaorong LI
Chinese Journal of Experimental Ophthalmology 2018;36(8):625-628
Objective To investigate the peripheral vascular findings in eyes with branch retinal vein occlusion (BRVO) and hemi-retinal vein occlusion (HRVO) using ultra-wide field fluorescein angiography (UWFFA),and analyze the influence of relative systemic factors on retinal vascular leakage.Methods A retrospective case-control study was designed.The 153 eyes of 146 patients with BRVO and 40 eyes of 40 patients with HRVO were include in Tianjin Medical University Eye Institute from September 2017 to March 2018.UWFFA was carried out in the patients,and the images were analyzed by Vantage Review software.The eyes were divided into two groups based on the whether the leakage occurred in other quadrant or fellow eye.The eyes with the fluorescence leakage only in the quadrant of affected vessel in late stage of UWFFA were in the RVO1 group,and the eyes with the fluorescence leakage in other quadrants or fellow eye besides affected vessel were in the RVO2 group.Relative past medical histories were recorded,such as hypertension,high cholesterol and diabetes mellitus.The influence of medical histories on vascular leakage in RVO1 group and RVO2 group with different histories was analyzed,respectively,and systemic factors which affected lcakage degree were evaluated.Results In 179 eyes with RVO,fluorescence leakage occurred in late stage of UWFFA besides affected vessel in 25 eyes (14.0%),including 19 eyes in the affected eyes (10.6%) and 6 eyes in fellow eyes (3.4%).Hypertension,high cholesterol and diabetes mellitus were found in 77,28 and 21 patients,respectively.In 77 hypertension patients,66 were in the RVO1 group,and 9 were in the RVO2 group (11.69%),and in 102 non-hypertension patients,86 were in the RVO1 group,and 16 were in the RVO2 group (15.69%),without significant difference was seen in the fluorescence leakage in other quadrants or fellow eye besides affected vessel between hypertension and non-hypertension patients (x2 =0.298,P =0.585).In 28 high cholesterol patients,24 were in the RVO1 group,and 4 were in the RVO2 group (14.29%),and in the 151 patients without high cholesterol,130 were in the RVO1 group,and 21 were in the RVO2 group (13.91%),without significant difference in the fluorescence leakage in other quadrants or fellow eye besides affected vessel between high cholesterol and non-high cholesterol (x2 =0.000,P =1.000).In 21 diabetes mellitus patients,17 patients were in the RVO1 group,and 4 patients were in the RVO2 group (19.05%),and in 158 patients without diabetes mellitus,137 were in the RVO1 group,and 21 were in the RVO2 group (13.29%),without significant difference was seen in the fluorescence leakage in other quadrants or fellow eye besides affected vessel between diabetes mellitus and non-diabetes mellitus (x2 =0.144,P=0.704).Conclusions Unexpected late peripheral retinal leakage can be seen on the UWFFA in the eyes with BRVO and HRVO.Hypertension,high cholesterol and diabetes mellitus are not the main cause of these findings.UWFFA can disclose more peripheral,wider retinal lesions.
10.Optical coherence tomography angiography in anterior ischemic optic neuropathy
Liying HU ; Zhiqing LI ; Xiaorong LI ; Rongguo YU ; Linni WANG ; Jin YANG
Chinese Journal of Ocular Fundus Diseases 2016;32(3):275-277
Objective To observe the optic disc perfusion in anterior ischemic optic neuropathy (AION) patients.Methods Forty eyes of 40 AION patients and 30 eyes of 30 normal subjects were included.The stage of the diseases was defined based on the course of the disease,including acute stage (less than 3 weeks) and recovery stage (more than 3 months).Optic disc blood flow area,outer vascular density and blood flow index were measured by optical coherence tomography angiography in all the subjects.Optic disc perfusion was observed in acute and recovery stage of disease.Results The optic disc blood flow area,outer vascular density and blood flow index were decreased of AION eyes in acute stage compared with the normal subjects,the difference was statistically significant (P<0.05);while the optic disc blood flow area,outer vascular density and blood flow index of AION eyes in the recovery stage showed no significant difference compared with normal subjects (P>0.05).Conclusion Disc perfusion is reduced in AION at the acute stage,but recovered at the recovery stage.

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