Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Exosomes are membranous vesicles secreted by cells and can be widely involved in intercellular communication, anti-inflammation, immunoregulation, etc.Mesenchymal stem cell (MSC), regulatory T cell (Treg), immature dendritic cell (imDC) and myeloid-derived suppressor cell (MDSC) are the main ocular surface-related exosomes origins.Exosomes derived from different cells play their roles by delivering different biological molecules to recipient cells.Exosomes derived from MSC play a positive role in ocular surface inflammation and immune-related diseases by inhibiting T cell proliferation, transforming macrophage phenotype, regulating T helper (Th) cell differentiation and up-regulating Treg expression, reduce neovascularization and inflammation, and foster a microenvironment to promote corneal wound healing at the same time.Exosomes derived from Treg contain inducible NO synthase and microRNA (miRNA) including miR-503, miR-330 and miR-9, which can interfere with cell cycle progression, induce apoptosis, induce the differentiation of other T cells into Treg phenotype, inhibit T cell allograft rejection to induce immune tolerance.Exosomes derived from imDC inhibit corneal allograft rejection by delivering miR-682.MDSC-derived exosomes promote Treg expansion in vivo and in vitro, inhibit the proliferation and cytotoxicity of activated T cells, and express miR-29a-3p and miR-93-5p, which can inhibit the differentiation of Th1 and Th17 cells.Given the anti-inflammatory and immunosuppressive effects of exosomes, this paper reviewed the studies on ocular surface inflammation and immune-related diseases such as corneal injury, mucopolysaccharide storage disease, dry eye, Sj?gren syndrome and ocular graft-versus-host disease.

Objective:To explore the changes in morphology and function of meibomian gland and the expressions of inflammatory factors and lipid metabolic factors in meibomian gland of diabetic mice.Methods:Fifty 8-week-old male C57BL/6 mice of clean degree were divided into normal control group ( n=20) and diabetes model group ( n=30) according to a random table.Diabetes model was established by the intraperitoneal injection of streptozotocin (60 mg/kg, 10 mg/ml). Mouse tail vein blood glucose ≥16.7 mmol/L was considered as successful modeling.Blood glucose was measured weekly, and body weight was compared between the two groups.Ten mice were randomly selected for fluorescein sodium staining of the cornea to evaluate the integrity of the corneal epithelium from both groups at an interval of 4 weeks.Five mice were randomly selected from the two groups and were sacrificed via anesthesia to collect meibomian gland tissue for hematoxylin and eosin staining in order to observe morphological changes at 8 and 16 weeks after modeling, respectively.At 16 weeks following modeling, mebomian gland of 5 mice randomly selected from both groups was stained with oil red O staining to observe the distribution of lipid.Real-time fluorescence quantitative-PCR was performed to detect the relative expressions of tumor necrosis factor (TNF)-α, pigment epithelium derived factor (PEDF), peroxisome proliferators-activated receptor γ (PPARγ), and adipose differentiation-related protein (ADFP) mRNA in meibomian gland.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Medical University Eye Hospital (No.TJYY20190630009). Results:The successful modeling rate of diabetes in mice was 100%, and the survival rate was 83.3% (25/30). The weight was significantly lower and the blood glucose level was higher in diabetes model group at 8 and 16 weeks after modeling in comparison with normal control group (all at P<0.05). There were significant differences in corneal fluorescein staining score among different time points in diabetes model group ( F=27.155, P<0.05). In diabetes model group, thinner wall of meibomian gland duct, enlarged lumen of the duct, dilated acini and oil red-stained lipid deposition in most acini were observed.At 16 weeks after modeling, the expressions of TNF-α, and PPARγ mRNA in meibomian gland of diabetes model group were 3.33±0.91 and 1.55±0.25, which were significantly higher than 1.00±0.16 and 1.00±0.27 of normal control group (both at P<0.05). The expression of PEDF mRNA in diabetes model group was 0.42±0.08, which was significantly lower than 1.00±0.34 in normal control group ( P<0.05). There was no significant difference in the ADFP mRNA expression between the two groups ( t=0.943, P=0.38). Conclusions:Inflammatory factors and lipid metabolic factors such as TNF-α, PEDF, and PPARγ may be involved in the pathogenesis of meibomian gland dysfunction induced by diabetes.

Objective:To compare the changes of corneal asphericity and higher-order aberrations after smart pulse technology-assisted transepithelial photorefractive keratectomy (Smart) for low and moderate myopia and to investigate the changes in the shape of the front corneal surface in patients with different diopters.Methods:A non-randomized controlled study design was used.Ninety-eight eyes of 54 patients with moderate or low myopia who underwent Smart surgery in Tianjin Medical University Eye Hospital from November 2018 to March 2019 were included.The 41 eyes of 23 patients with low myopia were set as the low-myopia group, and 57 eyes of 31 patients with moderate myopia were assigned as the moderate-myopia group.The Pentacam anterior segment analysis system was used to measure Q value, index of surface variance (ISV), corneal higher-order aberration (HOA), corneal vertical coma (Z 3-1), corneal horizontal coma (Z 31) and spherical aberration (Z 40) before surgery, 1 month and 3 months after surgery.The anterior surface morphology was compared between the low-myopia and moderate-myopia group.Pearson correlation analysis was used to analyze the correlations between measurement parameters.The study protocol was approved by an Ethics Committee of Tianjin Medical University Eye Hospital (No.2019KY-17). Written informed consent was obtained from each patient before surgery. Results:Corneal Q value, ISV, HOA and Z 40 were 0.445±0.191, 26.973±5.611, 0.671±0.142 and 0.384±0.188, respectively, in the low-myopia group at one month after surgery, which were significantly increased than corresponding preoperative values of -0.273±0.817, 13.784±2.376, 0.433±0.687 and 0.231±0.062 (all at P<0.05). Corneal Q value, ISV, HOA and Z 40 were 0.693±0.203, 34.038±5.773, 0.874±0.216 and 0.520±0.129, respectively, in the moderate-myopia group at one month after surgery, which were significantly increased than corresponding preoperative values of -0.309±0.104, 14.838±3.992, 0.409±0.081 and 0.228±0.089 (all at P<0.05). Corneal Q values, ISV, HOA and Z 40 in the moderate-myopia group were higher than those in the low-myopia group at different time points after surgery, showing significant differences between the two groups (all at P<0.05). There was no significant difference in postoperative 1-month and 3-month corneal Z 3-1 and Z 31 between the two groups (both at P>0.05). The results of correlation analysis showed that there were no significant differences in ΔQ value and ΔISV between the two groups, both of which were negatively correlated with spherical equivalent (ΔQ value: low-myopia group: r=-0.364, P=0.044; moderate-myopia group: r=-0.589, P<0.01; ΔISV: low-myopia group: r=-0.298, P=0.039; moderate-myopia group: r=-0.409, P=0.022). ΔQ value and ΔZ 40 were positively correlated in the moderate-myopia group ( r=0.348, P=0.009); there was no significant correlation between ΔQ value and ΔZ 40 in the low-myopia group ( r=0.180, P=0.266). Conclusions:The corneal high-order aberrations and ISV after Smart are increased in comparison with preoperative values in the low-myopia and moderate-myopia eyes, and the corneal Q values change from negative to positive.The effect of Smart on corneal asphericity is less in the low-myopia eyes.

Objective:To explore the damage of panretinal photocoagulation (PRP) to the subbasal nerve plexus (SNP) and its related mechanisms by comparing SNP changes in wide-field mosaic between before and after PRP treatment in diabetic patients.Methods:A randomized controlled study was conducted.Fifty-seven patients (114 eyes) with type 2 diabetes mellitus and binocular diabetic retinopathy (DR) stage IV to receive PRP treatment in Shanxi Eye Hospital from April to November 2019 were enrolled.The subjects were randomly divided into horizontal-vertical laser group and vertical-horizontal laser group according to a random number table.Twenty-nine eyes from 29 patients were assigned to the horizontal-vertical laser group with the photocoagulation sequence of temporal-nasal-inferior-superior.Twenty-eight eyes from 28 patients were assigned to the vertical-horizontal laser group with the photocoagulation sequence of inferior-superior-temporal-nasal.The severer eyes of each subject were chosen as the treatment eye and the contralateral eyes were chosen as the control eye.Corneal confocal laser scanning microscopy (CCM) was performed before PRP treatment, 1 week after each photocoagulation, and 1 month after the completion of PRP treatment to collect images of the SNP over an area of 2-3 mm around the whorl-like pattern.Captured images at each time were merged into one image by using the Photoshop CC 2017 image processing software, and then the nerve fiber length (NFL) of whorl-like pattern was measured by Neuron J image analysis software.McGill pain questionnaire was used to investigate the pain of patients after each photocoagulation.The NFL changes of SNP at different time points were compared between different eyes and different photocoagulation sequence groups.The study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Shanxi Eye Hospital (No.201804b). Written informed consent was obtained from each patient prior to entering the study cohort.Results:After PRP treatment, there were different degrees of neural structure loss of SNP nerve fibers in 11 treatment eyes, but there was no significant change in SNP nerve fibers in the control eyes.There were significant differences in NFL between the treatment eyes and the control eyes at various time points ( Feyes=2.020, P=0.039; Ftime=4.062, P=0.001). In the horizontal-vertical laser group, different degrees of neural structure loss on the photocoagulation side were found in SNP nerve fibers after the first and second photocoagulation.In the vertical-horizontal laser group, different degrees of neural structure loss on the photocoagulation side were found in SNP nerve fibers after the third and fourth photocoagulation.There was no significant difference in NFL of treatment eyes between the two groups ( Fgroup=0.099, P=0.754), but there was a significant difference in NFL at various time points before and after treatment ( Ftime=5.231, P<0.001). There were 9 (9/57) patients who complained of pain after PRP, which occurred at the first time of photocoagulation in 7 of them. Conclusions:SNP damage may occur after PRP in patients with DR, and SNP is prone to be damaged on the photocoagulation side when performing horizontal photocoagulation.

Objective:To estimate the correlation between DR and diabetic corneal nerve damage by comparing changes of corneal sub-basal nerve plexus (SNP) in the whorl-like region in different DR stages.Methods:In this cross-sectional study, 66 eyes of 66 type 2 diabetes patients aged 50-65 years old in Shanxi Eye Hospital from September 2018 to January 2019 were included.The subjects were divided into non-diabetic retinopathy group (NDR), non-proliferative diabetic retinopathy group (NPDR) and proliferative diabetic retinopathy group (PDR) accordingly, the right eyes were enrolled.20 eyes of 20 age and gender matched age-related cataract patients were also included as control group.All the subjects underwent confocal corneal microscopy to observe the morphology of SNP in the whorl-like region and measure the nerve fiber length (NFL) in this area.Covariance analysis using disease course as the covariate was used to analyze the differences of NFL value among groups, and Spearman rank correlation analysis was used to analyze the correlation between NFL value and DR stages.The study protocol was approved by the Ethics Committee of Shanxi Eye Hospital.Written informed consent was obtained from each patient prior to entering the study cohort.Results:The whorl-like region were observed in all the eyes.In the control group, nerve fibers were uniform in thickness, densely distributed with regular course, and most of the tested eyes had intact whorl-like structure.Nerve fibers in different DR groups all showed generally decrease in diameter and density, with increase in tortuosity, accompanied by different degrees of whorl-like structure loss.Eyes in the NDR group and NPDR group mainly showed nerve structure loss in the whorl-like center; while some eyes in the PDR group also showed nerve structure loss in the inferior and temporal of the whorl-like region.The NFL values were (21.08±4.74), (16.47±6.35), (14.95±3.90), and (11.61±3.24)mm/mm 2 in the control group, the NDR group, the NPDR group, and the PDR group, respectively, the overall difference was statistically significant ( F=10.541, P<0.001). The NFL value in the control group was significantly higher than those in the different DR groups, the differences were statistically significant (all at P<0.01). Spearman rank correlation analysis showed that there was a significant negative correlation between NFL value and DR stages ( rs=-0.356, P=0.003). Conclusions:Diabetic SNP damage occurs earlier than DR, and progress gradually with the development of DR; Different stages of DR are accompanied by different degrees of nerve structure loss; The structure loss begins at the whorl-like center and gradually develops to downward and the temporal side.The ophthalmologists should take the condition of ocular surface into account when treating ocular fundus diseases of diabetic patients.

An expert consensus about the clinical diagnosis and treatment of dry eye was documented in 2013 by a corneal expert group of Chinese Ophthalmological Society.However, due to the rapid development of diagnostic and therapeutic devices of dry eye, researoh on dry eye has made significont progress in China since then.Consequently, the existing expert consensus cannot meet the needs of clinical practice.It is therefore urgent to develop a series of standardized diagnosis and treatment protocols, and publish a new consensus of experts and an operating guideline.At the same time, basic, clinical, and translational research on dry eye should be promoted to provide better services to the patients with dry eyes.On January 12, 2019 many experts in the field of dry eye in China held a panel discussion of dry eye study in Guangzhou to analyze the current development status and trends in the field of dry eye in China and abroad.In that meeting, opinions and recommendations were put forward based on a new understanding of the definition of dry eye, new concepts of dysfunctional dry eye, advances its diagnosis and classification, refinement and standardization of dry eye treatment, and the future development of dry eye research.

Objective:To evaluate the clinical efficacy and safety of modified chitosan eye drops on rabbit Candida albicans keratitis model.Methods:Ten healthy female New Zealand rabbits were used to establish the superficial Candida albicans keratitis model by the corneal surface lens method in the right eye.Slit lamp microscopy and corneal scraping and microscopic examination were performed to preliminarily determine whether the keratitis model has been successfully established, the rabbits were then randomly divided into a model group and a modified chitosan group by the random number table method.The successfully established rabbit models which were determined by fungal culture results were retained.Five normal rabbits receiving no intervention served as a normal control group.The experimental eyes in the normal control and modified chitosan groups were treated with modified chitosan eye drops, Six times a day for one week, and subsequently four times a day for one week.No treatment was administered to the model group.The changes of corneal lesions and ocular surfaces were examined by slit lamp microscopy every day.At 1, 7, 14, 21 and 28 days after modeling, the eye condition and corneal clinical scores was assessed by slit lamp microscopy.The corneal conditions in each group was observed for two weeks after drug withdrawal.Results:The corneal scraping and microscopic examination results of eight rabbits models showed that the fungal hyphae and spores were positive.The fungal culture results showed that the separated pathogen was Candida albicans.The success rate of modeling was 80%(8/10). The clinical scores in the model group at 7, 14 and 21 days after modeling were 14.50±0.58, 6.25±0.50 and 2.50±0.58, respectively, and were significantly higher than 7.25±1.26, 2.75±0.50 and 1.25±0.50 in the modified chitosan group (all at P<0.05). In the model group, corneal edema was significantly aggravated, and the central white ulcer area was enlarged within seven days after modeling.Between 7 and 28 days after modeling, the corneal ulcer was gradually healed, while the central corneal scar and neovascularization were remained.The average healing time was (24.5±2.6)days.In the modified chitosan group, the corneal infiltration was significantly alleviated within seven days after modeling, and the fungal hyphae and spores of corneal scraping were negative on the 14th day after modeling.The average healing time in the modified chitosan group was (13.5±1.3)days, which was significantly shorter than that in the the model group (P<0.01). No recurrence of keratitis was observed in the modified chitosan group after two weeks of drug withdrawal.The cure rate was 100%.In the normal control group, the conjunctival hyperemia, corneal edema, and lesions were not observed during topical administration.Conclusion:The treatment with modified chitosan eye drop is effective in a rabbit superficial Candida albicans keratitis model, and have no obvious toxic effects on ocular tissues.

Objective To investigate the inhibitory effect of bromfenac sodium hydrate ophthalmic solution on corneal neovascularization (CNV) induced by alkali burn.Methods A total of 192 specific pathogen free (SPF) degree adult male Sprague-Dawley (SD) rats were used in this study.One hundred and seventy-two rats were chosen to establish CNV model with alkali burn in the right eyes.Following alkali burn,rats were randomly divided into CNV group,model control group,bromfenac sodium group and fluorometholone group,with 43 rats (43 eyes) in each group.Another 20 rats (40 eyes) served as normal control group.One day after modeling,the model control group,bromfenac sodium group and fluorometholone group received phosphate buffer saline (PBS),bromfenac sodium hydrate ophthalmic solution and 0.1％ fluorometholone eye drops,respectively.The state of cornea and anterior chamber and the growth of CNV of rats in each group were observed by slit-lamp microscope every day after modeling.At 1,3,7,14,21 and 28 days after modeling,the anterior segment photos of the experimental eyes were captured,and the percent of cornea areas covered by CNV was calculated.At 7,14 and 28 days after modeling,the eye tissue sections were stained with hematoxylin and eosin staining and immunohistochemistry staining to evaluate the expressions of CD45 and VEGF-A.Real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA)were used to detect the expression of COX-2 and VEGF mRNA and protein level.The use and care of the animals complied with the Statement of the Association for Research in Vision and Ophthalmology(ARVO).Results Each model group showed corneal edema and opacification 1 day after modeling.The corneal edema was aggravated 7 days after modeling.On the 14th day after modeling,the degree of corneal opacity and edema decreased gradually.On the 28th day after modeling,leucoma was observed in CNV group and model control group,and nebula was observed in bromfenac sodium group and fluorometholone group.At 7,14,21 and 28 days after modeling,the percentages of CNV areas in bromfenac sodium group and fluorometholone group were significantly lower than those in CNV group and model control group (all at P＜0.05).No significant difference was found in the percentage of CNV areas between bromfenac sodium group and fluorometholone group at various time points (all at P＞0.05).On the 7th day after modeling,the thinning of corneal epithelial layer,edema and arrangement disorder of stroma layer were observed,and the expression of VEGF-A was positive in all model groups;a small amount of CD45 positive inflammatory cell infiltrations were observed in CNV group and model control group.On the 14th and 28th day after modeling,CNV was seen in the center of cornea in CNV group and model control group;the epithelial keratosis and reduction of corneal edema were seen in each group,and no inflammatory cell infiltration was observed in each group.On the 7th day after modeling,the expressions of COX-2 and VEGF mRNA in CNV group and model control group were significantly higher than those in normal control group,bromfenac sodium group and fluorometholone group (all at P ＜ 0.05),the expressions of COX-2 and VEGF protein in bromfenac sodium group were significantly lower than those in CNV group (all at P＜0.05).The corneal peroration rate in model control group and bromfenac sodium group was 10％ (1 case in 10 rats).The corneal perforation rate in fluorometholone group was 30％ (3 cases in 10 rats).In each model group,10％ to 30％ rats had hyphema.Conclusions Bromfenac sodium hydrate ophthalmic solution can inhibit the formation and growth of CNV after alkali burn in rats.This effect may be mediated by regulating COX-2 expression,reducing inflammation and inhibiting VEGF production.

Objective To evaluate the effectiveness of intense pulsed light (IPL) therapy for meibomian gland dysfunction (MGD).Methods A prospective senal cases observational study was designed.Thirty patients with MGD (60 eyes)in the Tianjin Medical University Eye Hospital from October 2017 to April 2018 were enrolled.All the subjects received IPL therapy at baseline,1 week and 3 weeks after the baseline,respectively.Before each treatment and 3 months after treatment,subjective symptoms (ocular surface disease index [OSDI] questionnaire,Standard Patient Evaluation of Eye Dryness [SPEED] questionnaire),palpebral margin score,lipiview ocular surface interferometer lipid layer thickness (LLT) measurement,tear meniscus height (TMH) and noninvasive tear film breakup time (NIBUT) measurement were performed to detect and assess the IPL treatment effect.The safety of the IPL treatment was evaluated through the visual acuity and intraocular pressure.Results The OSDI score,SPEED score and the score of lipid excretion and secretion of meibomian gland before treatment were significantly higher than those of the other three time points (all at P＜0.01).The TMH before treatment was significantly lower than that of the other three time points (all at P＜0.01).No significant differences were obtained on first time NIBUT,blinking times and incomplete blink ratio among different time points (all at P＞0.05).After treatment,the average thickness of tear film lipid layer was slightly increased,and the secretion of tarsal gland was improved.There were no adverse reactions during the treatment and follow-up,no changes in corrected vision,and the intraocular pressure fluctuated within the normal range.Conclusions IPL therapy can alleviate the symptoms and signs of dry eye of MGD patients,and the effect can last for at least 3 months.IPL is an effective and safe method in treatment of MGD.