Advances in drug therapy of meibomian gland dysfunction / 中华实验眼科杂志

Meibomian gland dysfunction (MGD) is a chronic, diffuse meibomian gland disorder, which has complex pathogenesis and high prevalence.It has become one of the common ocular surface diseases in clinics, and its treatment has been the clinical research focus and a challenge over the years.The traditional treatments consist of lifestyle improvement, physical therapy, medical treatments and surgery, in which drug plays an important role.According to the etiology and pathogenesis of MGD, the applied drugs can be classified into three categories.The first category is to improve the quality of tears and the stability of tear film, including artificial tear and ocular surface lubricants, secretagogues (promoting the secretion of lipids, aqueous solution and mucin), androgens, etc.The second category is to improve the ocular surface microenvironment, including local and systemic antibiotics, glucocorticoid eyedrops, non-steroidal anti-inflammatory drugs, immunosuppressants, anti-mites drugs, etc.The third category is nutritional supplements and neuroprotectants, including vitamin D3, omega-3 fatty acids, autologous serum and so on.This review focused on widely-used and current emerging treatment options, aiming to provide references for clinical treatments and further study on MGD.

Changes in conjunctival mucin expressions in patients with first diagnosis of dry eye and its clinical significance / 中华实验眼科杂志

Objective:To investigate the expressions of MUC1, MUC4, MUC5AC and MUC16 in patients with first diagnosis of dry eye and their correlation with dry eye symptoms and signs.Methods:A cross-sectional study was conducted.Sixty-nine dry eye patients (69 eyes) as dry eye group and 40 normal volunteers (40 eyes) as normal control group were recruited in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Puotuo District Center Hospital from December 2016 to May 2018.Symptoms were evaluated by Chinese dry eye questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-Life Score Questionnaire (DEQS). Signs were assessed by tear film breakup time (TBUT), keratoconjunctival fluorescein sodium staining, and Schirmer I test.Conjunctival cells were collected by conjunctival impression cytology.The expression levels of MUC1, MUC4, MUC5AC and MUC16 mRNA in the two groups were determined by real-time fluorescence quantitative PCR.The correlation between the mRNA levels of conjunctival mucins and dry eye symptoms and signs were analyzed by Spearman correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Puotuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from each subject before any medical examination.Results:The expression levels of MUC1 and MUC16 mRNA in dry eye patients were 3.277(0.568, 5.790) and 1.815(1.048, 3.694), which were higher than 1.055(0.550, 2.010) and 1.024(0.541, 1.965) in normal control group (Z=819.00, P=0.008; Z=861.00, P=0.002). According to OSDI scores, MUC1 was mainly increased to 3.277(1.161, 6.226) in mild to moderate (12-32 points) dry eye patients (Z=9.04, P=0.029), and MUC16 was mainly increased to 1.968(1.074, 3.726) in severe (>32 points) dry eye patients (Z=12.24, P=0.007). MUC1 expression was positively correlated with TBUT, and was negatively correlated with corneal staining scoring and keratoconjunctival staining scoring ( r s=0.270, P=0.025; r s=-0.331, P=0.006; r s=-0.325, P=0.007). MUC16 expression was positively correlated with TBUT, and was negatively correlated with blurred vision scoring, symptom exacerbation scoring during reading, impact scoring of driving at night, impact scoring of computer and impact scoring of TV use ( r s=0.249, P=0.039; r s=-0.359, P=0.047; r s=-0.370, P=0.034; r s=-0.558, P=0.016; r s=-0.498, P=0.006; rs=-0.515, P=0.002). Conclusions:The gene expressions of MUC1 and MUC16 are higher in conjunctiva of dry eye patients.MUC1 mRNA expression is related to patients' signs.MUC16 mRNA expression is related to the quality of life of patients.

Concordance between Chinese dry eye diagnostic criteria and Asian dry eye diagnostic criteria / 中华实验眼科杂志

Objective:To analyze the clinical manifestations and signs of the first diagnosed dry eye patients, and to explore the concordance between the Chinese dry eye diagnostic criteria and the Asian dry eye diagnostic criteria.Methods:A cross-sectional multicenter study was conducted.One hundred and forty-one eyes of 141 patients who were diagnosed as dry eye for the first time were included in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Putuo District Center Hospital from December 2016 to May 2018.All patients completed the Chinese Dry Eye Questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) to evaluate the symptoms of dry eye.Tear film breakup time (BUT), keratoconjunctival fluorescein staining, meibomian gland morphology and function examination, and Schirmer Ⅰ test were performed to evaluate dry eye signs and the association between dry eye symptoms and signs.The eyes were divided into corneal staining positive and negative group according to the presence or absence of corneal fluorescein staining, and the dry eye symptoms of the two groups were assessed by the three questionnaires.The eyes were divided into tear-deficient dry eye, evaporative dry eye, mixed dry eye and abnormal tear dynamics dry eye to compare the difference of dry eye signs among the groups.This study adhered to the Declaration of Helsinki.The study protocol complied with Chinese regulations and rules on clinical trial research and was approved by Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Putuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from patients before entering the cohort.Results:The total score of Chinese Dry Eye Questionnaire, OSDI questionnaire and DEQS questionnaire was 12.00(7.00, 16.00), 25.00(17.50, 36.93) and 32.02(15.77, 52.34), respectively.It was found that 130 eyes (92.2%) had dryness, and 109 eyes (77.3%) had ocular fatigue and 108 eyes (76.6%) had foreign body sensation.Dryness, foreign body sensation, photophobia and poor vision were weakly positively correlated with corneal staining ( r=0.177、0.297、0.172, all at P<0.05). Pain, photophobia and poor vision were negatively correlated with tear secretion ( r=-0.178, -0.197, -0.174; all at P<0.05). It was found that 43.3% of dry eye patients had used visual display terminals.Among the 141 eyes, 75 eyes (53.2%) were with over evaporation dry eye, 43 eyes (30.5%) with mixed dry eye, 18 eyes (12.8%) with aqueous-deficient dry eye and 3 eyes (2.1%) with abnormal tear dynamics dry eyes. Conclusions:Initial diagnosis of dry eye patients is mainly mild to moderate.Dry eye signs and symptoms are correlated.Over evaporation dry eye is the most common type of dry eye.The concordance between the Chinese dry eye diagnostic criteria and the Asian Dry Eye Society diagnostic criteria reaches 97.2%.

Role of complement dysregulation in age-related macular degeneration / 中华实验眼科杂志

Age-related macular degeneration (AMD) is a common cause of blindness, which is still short of effective therapies.As a complex disease affected by genetical, metabolic and nutritional factors, a key factor to promote the occurrence and development of AMD is chronic inflammation.In recent years, the etiological role of abnormal complement activation in AMD has attracted lots of attention.Genetic analysis has identified a number of complement-related genes, especially CFH, affecting the susceptibility of AMD.Moreover, in vitro and in vivo studies have found that abnormal ocular and systemic complement activations are closely related to the pathological alterations of AMD, including Bruch membrane changes, drusen formation, chronic retinal inflammation and choroidal neovascularization.The dysregulation of complement activation cascades causes the damage of retinal cells, which eventually leads to the pathological changes of AMD.Accordingly, complement system has become a target for new anti-AMD therapy development.This review summarized the pathological characteristics of AMD, complement-related risk genes for AMD, and the role of abnormal complement activation in promoting the progression of AMD, so as to find new targets for AMD treatment.

Dry eye consensus by Asian Dry Eye Society: interpretation / 中华实验眼科杂志

Asia Dry Eye Society (ADES) is the leading dry eye academic organization in Asia.Based on Dry Eye Work Shop (DEWS)Ⅰin 2007 and DEWSⅡin 2017 released by Tear Film and Ocular Surface Association (TFOS), ADES developed a systematic study on the definition, diagnosis, classification and managing strategy of dry eye in Asia during past seven years.A new classification consensus report of Asia dry eye was finally proposed in 2020, which is helpful for ophthalmologists and patients to understand the pathogenesis of dry eye and make the identification and precision therapy of dry eye clearer and more feasible. New Perspectives on Dry Eye Definition and Diagnosis: A Consensus Report by the Asia Dry Eye Society on The Ocular Surface in 2017, and A New Perspective on Dry Eye Classification: Proposal by the Asia Dry Eye Society on Eye and Contact Lens in 2020 are guidelines for dry eye management in Asia.These two consensuses were interpreted in this paper, including new concepts and methods of the definition, diagnosis, classification and treatment of dry eye.

New understanding and trends in the diagnosis and management of dry eye / 中华实验眼科杂志

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.

Effects of 0.3％ sodium hyaluronate ophthalmic solution in the treatment of mild-to-moderate dry eye patients:a multi-center clinical study / 中华实验眼科杂志

Objective To evaluate the efficacy of 0.3％ sodium hyaluronate ophthalmic solution in mild-to-moderate dry eye patients.Metbods A prospective,multicenter,and self-controlled clinical trial was performed on 200 patients who were diagnosed as mild-to-moderate dry eye from January 2015 to June 2017 in Eye Institute of Xiamen University,Eye & ENT Hospital of Fudan University,Zhongshan Ophthalmic Center,Xiangya Hospital Central South University,Eye Hospital of Wenzhou Medical University,and Beijing Tongren Hospital,Capital Medical University.The study protocol was approved by the Ethics Committees of Eye Institute of Xiamen University,written informed consent was obtained from each patient prior to any medical examination.All patients were treated with 0.3％ sodium hyaluronate ophthalmic solution 6 times per day (one drop each time) for 28 days.Corneal fluorescein sodium staining,tear film break-up time (BUT),Schirmer Ⅰ test (S Ⅰ t),degree of conjunctival hyperemia,eyelid margin,meibomian gland secretion,secretory capacity of meibomian gland and subjective symptoms were assessed at baseline,on the 14th day and 28th day after treatment.Bulbar impression cytology was evaluated at baseline and on the 28th day after treatment.Irritation of 0.3％ sodium hyaluronate ophthalmic solution was estimated on the 14th day and 28th day after treatment.Results The total score of subjective symptoms,BUT,S Ⅰ t,degree of conjunctival hyperemia were significantly different among different treatment time points (F =108.969,27.598,16.838,36.750;all at P＜0.01).Compared with before treatment,the total score of subjective symptoms was significantly decreased,the degree of conjunctival hyperemia and the total corneal fluorescein sodium staining point number were significant decreased on the 14th day and 28th day after treatment.The total score of subjective symptoms,degree of conjunctival hyperemia and total corneal fluorescein sodium staining point number on the 28th day after treatment were significant lower than those on the 14th day after treatment.Compared with before treatment,the BUT was significantly longer and the S Ⅰ t scores were significantly increased on the 14th day and 28th day after treatment.The BUT on the 28th day after treatment was significantly longer than that on the 14th day after treatment;no significant difference in S Ⅰ t was observed between the 28th day and the 14th day after treatment.The scores of palpebral margin change,meibomian gland secretory ability and secretion characteristics were not significantly different among different treatment time points(H=0.255,2.356,0.294;all at P＞0.05).The impression cytology grade on the 28th day after treatment was 1.08±0.74,which was significantly lower than 1.53±0.76 before treatment (t =5.979,P＜0.01).The number of goblet cells on the 28th day after treatment was significantly higher than that before treatment (U =1 806.500,P＜ 0.01).On the 14th day after treatment,70％ of the patients indicated that the drug was non-irritating,and no patient had intolerable irritation affecting daily lives.All patients had good tolerance to this drug.Conclusions The use of 0.3％ sodium hyaluronate eye drops can improve the symptoms and signs of mild to moderate dry eye,which can be widely used for mild-to-moderate dry eye patients in clinic.

Sleep deprivation disrupts the lacrimal system and induces dry eye disease

Sleep deficiency is a common public health problem associated with many diseases, such as obesity and cardiovascular disease. In this study, we established a sleep deprivation (SD) mouse model using a ‘stick over water’ method and observed the effect of sleep deficiency on ocular surface health. We found that SD decreased aqueous tear secretion; increased corneal epithelial cell defects, corneal sensitivity, and apoptosis; and induced squamous metaplasia of the corneal epithelium. These pathological changes mimic the typical features of dry eye. However, there was no obvious corneal inflammation and conjunctival goblet cell change after SD for 10 days. Meanwhile, lacrimal gland hypertrophy along with abnormal lipid metabolites, secretory proteins and free amino-acid profiles became apparent as the SD duration increased. Furthermore, the ocular surface changes induced by SD for 10 days were largely reversed after 14 days of rest. We conclude that SD compromises lacrimal system function and induces dry eye. These findings will benefit the clinical diagnosis and treatment of sleep-disorder-related ocular surface diseases.

A new method for constructing engineered corneal epithelium based on embryonic stem cells / 中华实验眼科杂志

Objective To construct engineered corneal epithelium from embryonic stem cells (ESCs) using Rock inhibitor combined with hypoxia-normoxia culture condition. Methods Human ESC line H1 was induced to differentiate into epithelial-like cells by addition of retinoic acid (RA) and bone morphogenetic protein 4(BMP4) in the differentiation medium under the adherent culture condition. The ESCs derived epithelial-like cells were expanded in the mixed medium of SHEM and KSFM with the mixture ratio of 1 : 2 with or without Rock inhibitor Y27632. The H1 derived epithelial-like cells were seeded on the denuded ammonic membrane to construct engineered corneal epithelium under hypoxia,normoxia and hypoxia-normoxia culture conditions,respectively. The inducted effect of ESCs into epithelial-like cells,the expansion ability of the epithelial-like cells and the characteristics of the constructed engineered corneal epithelium were evaluated by morphological observation, real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) and immunofluorescence technology. Results Compared with the control group,the relative expressions of ESCs marker Oct4 mRNA, Notch signaling pathway related factors Notch1 and Jagged1 mRNA,and Wnt signaling pathways related factors c-myc and Cyclin D1 mRNA were significantly reduced, and the relative expressions of cutaneous ectoderm markers p63 and K18 mRNA were significantly increased at day 8 after induction in the induced group,with significant differences between them (t =14.63,20.15,93.50,11.60, 19.30,18.44,22.63;all at P<0.05). Compared with the without Y27632 group,the relative expressions of p63 and K14 mRNA,Notch signal pathway receptor Notch1 and Jagged1 mRNA were significantly increased,and Wnt signaling pathways downstream targeted gene c-myc and CylinD1 mRNA were significantly decreased at day 8 after induction in the Y27632 group,with significant differences between them (t =20.29,59.22,2.90,39.59,5.32,10.14;all at P<0.05),and the relative expression of K18 mRNA in the two groups was not significantly changed(t=1.38,P>0.05). The ESCs derived epithelium and constructed under hypoxia-normoxia culture condition showed more obvious stratification and tighter cell arrangement in comparison with those cells cultured in consistent hypoxia culture condition or normoxia culture condition. Epithelial markers Pan-CK and K18 as well as epithelial progenitor cell markers p63 and K14 expressed in the whole cell layers of the ESCs derived epithelium constructed under hypoxia-normoxia culture condition. Conclusions The addition of Y27632 enhances the proliferation ability of H1 derived epithelial cells and actives Notch signaling pathway and inhibits Wnt signaling pathway. The culture and construction in the expansion medium with Y27632 under the hypoxia-normoxia culture condition can promote the stratification of H1 derived engineered corneal epithelium.

Focus on the clinical application of limbal stem cells / 中华实验眼科杂志

Limbal stem cells (LSCs) transplantation is an effective surgical treatment to address limbal stem cells deficiency ( LSCD) resulting from Stevens Johnson's syndrome or corneal chemical burn. LSCs transplantation has been reported as the successful stem cell therapy for bodybuilding, while it still faces a number of daunting challenges. Researchers should pay more attention to substitute seed cell, novel cell carrier materials, effective expansion method,niche modification and immune rejection,so that patients with ocular surface diseases would get fullly therapeutic benefit.

Emphasizing the diagnosis and treatment of Demodex blepharitis / 中华实验眼科杂志

Blepharitis is one of the common eye diseases,it may cause ocular irritation symptoms,and even cause damage of visual function,if it involves the meibomian gland and cornea.Recent studies have shown that Demodex infestation may be an important but under-estimated cause of blepharitis,its diagnosis and treatment become the focus of blepharitis research,clinical doctors should pay adequate attention to this.Demodex blepharitis still faces many uncertain problems and challenges.In this paper,the controversial problems of Demodex blepharitis diagnosis and treatment,combined with domestic and foreign research results and the author's experience was analyzed,and we also discussed that how to improve the accuracy of clinical diagnosis and improve the treatment effect of Demodex blepharitis.Herein,we emphasize on the diagnosis and treatment options of Demodex blepharitis.Early detection of the pathogen and prompt treatment would ultimately improve the prognosis of Demodex blepharitis.

Effects of 0. 3％ sodium hyaluronate ophthalmic solution in the treatment of mild-to-moderate dry eye patients:a multi-center clinical study / 中华实验眼科杂志

Objective To evaluate the efficacy of 0. 3％ sodium hyaluronate ophthalmic solution in mild.to. moderate dry eye patients. Methods A prospective,multicenter,and self.controlled clinical trial was performed on 200 patients who were diagnosed as mild.to.moderate dry eye from January 2015 to June 2017 in Eye Institute of Xiamen University,Eye &ENT Hospital of Fudan University,Zhongshan Ophthalmic Center,Xiangya Hospital Central South University, Eye Hospital of Wenzhou Medical University, and Beijing Tongren Hospital, Capital Medical University. The study protocol was approved by the Ethics Committees of Eye Institute of Xiamen University,written informed consent was obtained from each patient prior to any medical examination. All patients were treated with 0. 3％ sodium hyaluronate ophthalmic solution 6 times per day ( one drop each time) for 28 days. Corneal fluorescein sodium staining,tear film break.up time (BUT),SchirmerⅠtest (SⅠt),degree of conjunctival hyperemia,eyelid margin,meibomian gland secretion,secretory capacity of meibomian gland and subjective symptoms were assessed at baseline,on the 14th day and 28th day after treatment. Bulbar impression cytology was evaluated at baseline and on the 28th day after treatment. Irritation of 0. 3％ sodium hyaluronate ophthalmic solution was estimated on the 14th day and 28th day after treatment. Results The total score of subjective symptoms,BUT,SⅠt,degree of conjunctival hyperemia were significantly different among different treatment time points( F=108. 969,27. 598,16. 838,36. 750;all at P<0. 01). Compared with before treatment,the total score of subjective symptoms was significantly decreased, the degree of conjunctival hyperemia and the total corneal fluorescein sodium staining point number were significant decreased on the 14th day and 28th day after treatment. The total score of subjective symptoms,degree of conjunctival hyperemia and total corneal fluorescein sodium staining point number on the 28th day after treatment were significant lower than those on the 14th day after treatment. Compared with before treatment,the BUT was significantly longer and the SⅠt scores were significantly increased on the 14th day and 28th day after treatment. The BUT on the 28th day after treatment was significantly longer than that on the 14th day after treatment;no significant difference in SⅠt was observed between the 28th day and the 14th day after treatment. The scores of palpebral margin change,meibomian gland secretory ability and secretion characteristics were not significantly different among different treatment time points(H=0. 255,2. 356,0. 294;all at P>0. 05). The impression cytology grade on the 28th day after treatment was 1. 08±0. 74,which was significantly lower than 1. 53±0. 76 before treatment (t=5. 979, P<0. 01). The number of goblet cells on the 28th day after treatment was significantly higher than that before treatment(U=1806. 500,P<0. 01). On the 14th day after treatment,70％ of the patients indicated that the drug was non.irritating,and no patient had intolerable irritation affecting daily lives. All patients had good tolerance to this drug. Conclusions The use of 0. 3％ sodium hyaluronate eye drops can improve the symptoms and signs of mild to moderate dry eye,which can be widely used for mild.to.moderate dry eye patients in clinic.

To promote the development and translation of eye tissue engineering study in China / 中华实验眼科杂志

Eye tissue engineering is a new direction of scientific research.It applies body tissues,cells or scaffolds with specific biological activities in vitro or in vivo to construct ocular tissues or organs in order to promote and improve the ocular physical functions by maintaining,repairing and inducing tissue regeneration.With the increase of aging population and average life expectancy,eye tissue engineering and regenerative medicine will become an important researching area of ophthalmology,and its relevant products and technologies can become a platform for future alternative medical equipment applications in ophthalmology.Greater efforts on the basic research and continuous innovation of eye tissue engineering technologies in China,including translational medicine from basic research to industrial production and medical applications,will significantly build up the foundation of eye tissue engineering industry in China and greatly improve its competitiveness in international medical marketing,and these research achivements will provide new power for the development of ophthalmology in China.

Efficacy of tacrolimus eyedrops topical application for herpes simplex disciform stromal keratitis and its influence on tear / 中华实验眼科杂志

Background Herpes simplex virus (HSV) disciform stromal keratitis is a T cell-mediated delayed-type hypersensitivity of corneal stroma.The treatment of HSV disciform stromal keratitis is the combination of glucocorticoid and antiviral drug before.However,the therapy is limited for intolerantble patients to glucocorticoid.In addition,the adverse reactions following usage of glucocorticoid can not be ignored.FKS06 solution is proved to has the immunosuppressive and antiinflammatory acttions with less side effects than glucocorticoid drug.But the study on the application of FK506 solution in treatment of HSV disciform stromal keratitis is lack.Objective This prospective clinical trail was to evaluate the efficacy of topical tacrolimus for HSV disciform stromal keratitis and its safety.Methods A prospective study was performed on 18 consecutive cases (18 eyes) who were diagnosed as active HSV disciform stromal keratitis from June 2011 to June 2012 in Zhongshan Ophthalmic Center under the approval of the Ethic Committee of Zhongshan Ophthalmic Center and informed consent of the patients,including 3 patients with refractory to prior steroid eyedrops.All patients received a combination topical tacrolimus eyedrops 4 times per day with topical and systemic anti-viral therapy for mean (56.0±7.9) days.Corneal thickness by slit lamp biomicroscope,visual acuity,intraocular pressure,corneal fluorescein staining,Schirmer Ⅰ test (S Ⅰ t) and tear breakup time (BUT) were performed on the patients before and 1 month,2 months after treatment and at the drug withdrawal to assess the treating efficacy of FK506,and the adverse reactions of eyes were recorded.Results Corneal edema was alleviated in (8.3 ± 2.5) days after treatment in all the patients and returned to normality in (25.3±11.5) days.Corneal edema of 2 eyes with refractory to previous steroid eyedrops showed a slower recovery procedure than that of the others.Corneal fluorescence staining scores were 4 (6,2),1 (2,1),1 (1,0) and 0 (1,0) before and 1 month,2 months and at drug withdrawal,respectively,with a significant difference among the four time points (H=39.90,P＜0.001),and the scores were significantly lower after treatment than before (all at P＜0.01).The S Ⅰ t values were (6.78±1.90),(7.39±3.53),(8.06±2.92) and (8.11±3.05) mm/5 min,respectively in the 4 time points,without statistically significant difference among various time points (F =0.94,P =0.43).The BUT values were (0.39 ± 0.50),(1.11 ± 0.90),(2.00 ± 1.08) and (3.39 ± 0.92) seconds,respectively,showing a significant difference among the 4 time points (F=34.54,P＜0.01) and had the increased values after treatment of FK506.Recurrence was seen in 2 eyes in 2 months and 5 months after cessation of tacrolimus.However,the eyes were healed after a second round regimen.No elevation of intraocular pressure and secondary infection were found in the patients during the treatment and follow-up period.Conclusions The combination therapy of tacrolimus with antiviral drug is effective and safe for HSV disciform stromal keratitis by alleviating corneal edema and promoting the rehabilitation of tear film.

Remote Slit Lamp Microscope Consultation System Based on Web / 中国医疗器械杂志

To realize the remote operation of the slit lamp microscope for department of ophthalmology consultation, and visual display the real-time status of remote slit lamp microscope, a remote slit lamp microscope consultation system based on B/S structure is designed and implemented. Through framing the slit lamp microscope on the website system, the realtime acquisition and transmission of remote control and image data is realized. The three dimensional model of the slit lamp microscope is established and rendered on the web by using WebGL technology. The practical application results can well show the real-time interactive of the remote consultation system.

Clinical efficacy of 0.1% pranoprofen in treatment of dry eye patients: a multicenter, randomized, controlled clinical trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dry eye is a multifactorial disease of the tears and the ocular surface. This study aimed to investigate the clinical efficacy of a non-steroidal anti-inflammatory drug, pranoprofen, in the treatment of dry eye.</p><p><b>METHODS</b>It is a prospective, multi-center, randomized, controlled, parallel group study. One hundred and fifteen patients with mild to moderate dry eye disease (55-60 in each treatment group) participated in this multi-center study. Patients were randomly administered with eyedrops containing 0.1% pranoprofen (PRA) plus 0.1% sodium hyaluronate (SH) or SH only, three times daily for 28 days, followed by a 1-week after treatment observation. Dry eye symptom score (DESS), fluorescein corneal staining (FLCS), tear break-up time (TBUT), and Shirmer 1 tear test (ST1, without anesthesia) were evaluated or conducted before treatment and at each study visit. Conjunctival impression cytology was taken from the patients treated with PRA plus SH before and after treatment and real-time polymerase chain reaction (RT-PCR) was performed to detect the changes of human leukocyte antigen DR (HLA-DR) and intercellular adhesion molecule 1 (ICAM-1).</p><p><b>RESULTS</b>Patients treated with PRA plus SH showed gradual improvements of DESS, FLCS, and TBUT. Between-group comparisons of FLCS and TBUT have statistically significant differences from day 14. Good tolerance with no severe adverse events was found in both groups. Patients treated with PRA plus SH had a reduced expression level of HLA-DR and were statistically different after 28 days of therapy.</p><p><b>CONCLUSIONS</b>The application of PRA at a dose of 0.1% was well tolerated and benefited to the patients with mild to moderate dry eye disease. The underlying mechanism of its efficacy may be associated with the reduction of inflammatory factors of conjunctival epithelial cells.</p>

Preparation and Identification of Anti-lactoferrin Single Chain Fv Antibody / 医学研究杂志

Objective To prepare a specific anti-lactoferrin single chain variable fragment(ScFv).Methods Anti-lactoferrin clones were screened from a 'naive' phage antibody library against the immobilized lactoferrin antigen,then the clones were transformed to the E.coli HB2151 to give soluble expression of antibody fragments.The culture supernatant containing ScFv was purified by immobilized metal affinity chromatography,and then determined with SDS-PAGE and ELISA.Results The results demonstrated that ScFvs were specific;they did not react with transferrin,lysozyme and bovine serum albumin in ELISA.The SDS-PAGE showed that the ScFvs had high purity through affinity chromatography and the molecular weight of them was about 32 kD.Conclusions The successful generation of the ScFvs against lactoferrin provides a basis for further study and clinical applications for dry eye and other ocular diseases.

Experimental research on effect of human mesenchymal stem cells induced by shenqi fuzheng injection in cerebral infarction / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of shenqi fuzheng injection (SFI) in inducing differentiation of human mesenchymal stem cells (hMSCs) in brain stem and its effect on nervous function in model rats of cerebral infarction.</p><p><b>METHODS</b>Middle cerebral artery occlusion model rats were made, and hMSCs was injected into their brain after being amplified in vitro and incubated with SFI for 0.5 h, then the survival, migration and differentiation of hMSCs in brain stem as well as the change of nervous function in model rats were observed.</p><p><b>RESULTS</b>The post-transplantation reject reaction to hMSCs was low, it could survive as long as 6 weeks or more. No difference in area of infarction was shown before and after transplantation. Immunohistochemical staining showed that hMSCs expressed human neuron specific enolase (NSE), neurofilament (NF) and glial fibrillary acid protein (GFAP). The limb-kinetic function and tactile perception were improved in the model rats.</p><p><b>CONCLUSION</b>SFI can induce hMSCs differentiate into neurons in vivo, and hMSCs may be the ideal germinal cells for treating cerebral infarction.</p>

Overexpression of type I growth factor receptors in pterygium / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the expression of the type I growth factor receptor family [epidermal growth factor receptor (EGFR), ErbB2 and ErbB3] by the epithelial cells in pterygium.</p><p><b>METHODS</b>Immunoflourescent staining and Western blotting were performed to detect the expression pattern and quantity of EGFR, ErbB2 and ErbB3 proteins in the epithelia of 15 patients with primary pterygium and 12 subjects with normal conjunctiva.</p><p><b>RESULTS</b>In immunofluorescent staining, the EGFR protein was present in the basal cells while the ErbB2 and ErbB3 were expressed by the superficial cells in normal conjunctival epithelium. Of the pterygium cases 15, 11 were stained by EGFR, ErbB2 and ErbB3 in the full thickness of the epithelium and showed stronger staining compared with the control group. Four of them showed a similar staining pattern to the normal conjunctiva group. The density of protein bands detected by Western blotting for all three growth factor receptors was consistent with the immunofluorescent staining. Compared with normal conjunctiva, stronger protein bands of these three receptors were found in all of the pterygium specimens, in which EGFR, ErbB2 and ErbB3 were expressed in the full thickness, as shown by immunofluorescent staining.</p><p><b>CONCLUSIONS</b>The increased expression of EGFR, ErbB2 and ErbB3 proteins was present in pterygium, which indicated that pterygium is a disorder with abnormal proliferation. The abnormal expression of EGFR, ErbB2 and ErbB3 by the epithelium and the communication with cytokines in the stroma in pterygium may be a key pathogenic factor in this disorder.</p>

Doxycycline induces apoptosis in THP-1 cells / 中国病理生理杂志

AIM: This study was designed to investigate the apoptotic effect of doxycycline in THP-1 cells.METHODS: After differentiated by PMA, THP-1 cells were treated with doxycycline at different concentrations ranging from zero to 80 mg/L. The morphological changes of THP-1 cells were observed under light microscope. MTT assay were used to examine the effects of doxycycline on proliferation of THP-1 cells. Apoptotic THP-1 cells were measured by Annexin-V flow cytometry analysis and TdT-mediated dUTP nick end labeling assay.RESULTS: Treated with a certain concentration of doxycycline, differentiated THP-1 cells contracted and turn round, a number of cells were dead. MTT assay and positive Annexin V-FITC on cell membrane and TUNEL assay showed that doxycycline induced apoptosis in THP-1 cells in a dose-dependent manner.CONCLUSION: Doxycycline induces apoptosis in THP-1 cells in a dose-dependent manner.