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Dry environment on the expression of lacrimal gland S100A9,Anxa1,and Clu in rats via proteomics

International Journal of Ophthalmology(English edition) 2024年第3期17卷 435-443页

作者： Yi-Lin Sun A-Yuan Cui Li-Xin Wang Wang-Wang Zhang Hong Shi College of Traditional Chinese Medicine Xinjiang Medical UniversityUrumqi 830011Xinjiang Uygur Autonomous RegionChina Research on High Incidence of Diseases in Xinjiang Region Key Laboratory of the Ministry of Education(Xinjiang Medical University)Urumqi 830011Xinjiang Uygur Autonomous RegionChina

●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-rel

关键词： dry eye lacrimal gland S100A9 Clu Anxa1 environment rats

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Treatment of lacrimal gland adenoid cystic carcinoma:a systematic review and Meta-analysis

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 164-172页

作者： Hai-Han Yan Rui Liu Nan Wang Liang-Yuan Xu Qi-Han Guo Jing Li Jian-Min Ma Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Ophthalmology&Visual Sciences Key LaboratoryBeijing 100730China

AIM:To evaluate lacrimal gland adenoid cystic carcinoma(LGACC)of prognosis in patients who underwent different treatment regimens.METHODS:We searched PubMed,EMBASE,and the Cochrane Library for studies done on the treatment of LGACC,between January 1987 and April 2022.A Metaanalysis was conducted to pool the 5-year overall survival rate(OR),and the 5-year recurrence rate(RR)and 5-year metastasis rate(MR)were assessed.RESULTS:The 30 studies involved 585 patients were included in the Meta-analysis.The pooled 5-year OR with surgery alone was 50%,the 5-year RR was 63%,and the 5-year MR was 34%.The pooled 5-year OR with surgery and adjuvant radiotherapy combined was 67%(95%CI 61%,73%),the 5-year RR was 41%,and the 5-year MR was 35%.The pooled 5-year OR with surgery and adjuvant chemoradiotherapy combined was 72%(95%CI 59%,84%),the 5-year RR was 48%,and the 5-year MR was 36%.The pooled 5-year OR with surgery,intra-arterial cytoreductive chemotherapy,and adjuvant chemoradiotherapy combined was 78%(95%CI 68%,89%),the 5-year RR was 15%,and the 5-year MR was 27%.CONCLUSION:Comprehensive treatment is more effective than surgery alone.Surgery combined with intraarterial chemotherapy and adjuvant chemoradiotherapy seems to add value to the therapeutic effect of comprehensive treatment of LGACC but further high-quality research is required to validate this.

关键词： adenoid cystic carcinoma lacrimal gland Meta-analysis

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Different serum levels of IgG and complements and recurrence rates in IgG4-positive and negative lacrimal gland benign lymphoepithelial lesion

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International Journal of Ophthalmology(English edition) 2023年第6期16卷 876-883页

作者： Rui Liu Nan Wang Jin-Jin Wang Jing Li Xin Ge Jing-Xue Zhang Jian-Min Ma Beijing Ophthalmology and Visual Sciences Key Laboratory Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing 100730China

·AIM:To analyze the differences in immune indicators and prognosis between Ig G4-positive and negative lacrimal gland benign lymphoepithelial lesion(LGBLEL).·METHODS:This was a single-center retrospective clinical study including 105 cases of Ig G4-positive LGBLEL and 41 cases of Ig G4-negative LGBLEL.Basic information,related indicators of peripheral venous blood samples using immunoscattering turbidimetry,treatment(partial surgical excision and glucocorticoid therapy)and prognosis(recurrence and death)were collected.Survival curves for recurrence were created using the Kaplan-Meier analysis.Univariate analysis and multivariate regression analysis were used to analyze prognostic factors.·RESULTS:The mean age was 50.10±14.23y and 44.76±11.43y(P=0.033)in Ig G4-positive and negative group respectively.The serum C3 and C4 was lower in Ig G4-positive group(P=0.005,P=0.002),while the serum Ig G and Ig G2 was higher in Ig G4-positive group(P=0.000 and P=0.008).Twenty-one cases had recurrence in Ig G4-positive group and 3 cases recurrence in Ig G4-negative group.The 5-year recurrence-free cumulative percentages of Ig G4-positive group was 81.85%,and 83.46%in the Ig G-negative group(P=0.216).The history of preoperative glucocorticoid therapy,serum C4,Ig G1 and Ig G2 were the factors affecting recurrence in Ig G4-positive group,while serum C4,and Ig G1 were the factors affecting recurrence of LGBLEL.·CONCLUSION:Serum C4 and Ig G1 are the factors affecting recurrence of LGBLEL,while the Ig G4 does not affect recurrence of LGBLEL.

关键词： benign lymphoepithelial lesion lacrimal gland IgG4 complement prognosis

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Comparison of biological behavior of lacrimal gland adenoid cystic carcinoma with high-grade transformation cells

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International Journal of Ophthalmology(English edition) 2023年第2期16卷 163-171页

作者： Chuan-Li Zhang Li-Min Zhu Xun Liu Mei-Xia Jiang Ting-Ting Lin Yan-Jin He Oculoplastic and Orbital Disease Department Tianjin Medical University Eye HospitalEye Institute and School of OptometryTianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseTianjin 300384China Tianjin Eye Hospital Optometry Center Tianjin 300384China

AIM:To evaluate the differences between human lacrimal gland adenoid cystic carcinoma with high-grade transformation(LACC-HGT)primar y cells cultured by high-grade transformation tissue and non-high-grade transformation(non-HGT)primary cells cultured by non-highgrade transformation tissue in proliferation,metastasis,drug susceptibility,and genes.METHODS:LACC-HGT primary cells were established by tissue block culture,and the 4^(th)to 10^(th)generation primary cells were selected as research objects.The cells were preliminarily identified by immunofluorescent staining.The differences between non-HGT and LACC-HGT primary cells in terms of proliferation,metastasis,and drug susceptibility were compared by cell counting kit-8(CCK-8)assay,wound healing,and drug sensitivity experiments.Differentially expressed genes were screened using mRNA array.Gene expression was analyzed using real-time quantitative polymerase chain reaction(RT-qPCR).RESULTS:LACC-HGT primary cells were successfully cultured by tissue block culture.Immunofluorescence staining results showed that cytokeratin(CK)and CK7 expression levels were positive in LACC-HGT primary cells.CCK-8 results showed that the proliferation ability of LACCHGT cells was significantly higher than that of non-HGT cells.Wound healing experiment showed that the migration ability of LACC-HGT cells was significantly higher than that of non-HGT cells.LACC-HGT cells were also less sensitive to cisplatin and paclitaxel than non-HGT cells.Compared with non-HGT cells,9566 differentially expressed genes were found in LACC-HGT primary cells,of which 5162 were upregulated and 4404 were down-regulated.The expression of N-acetylneuraminate pyruvate lyase(NPL),MARVEL domain containing 3(MARVELD3),syntabulin(SYBU),and allograft inflammatory factor 1(AIF1)was higher in LACCHGT cells than in non-HGT cells,whereas that of periostin(POSTN)was lower.CONCLUSION:LACC-HGT primary cells have faster proliferation,stronger migration ability,and poorer sensitivity to chemotherapy drugs than non-HGT prima

关键词： lacrimal gland lacrimal gland adenoid cystic carcinoma high-grade transformation primary cell culture biological behavior mRNA array

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lacrimal gland tumors in Turkey：types,frequency,and outcomes

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International Journal of Ophthalmology(English edition) 2018年第8期11卷 1296-1302页

作者： Yagmur Seda Yesiltas Ahmet Kaan Gundiiz Esra Erden Carol L. Shields Department of Ophthalmology Ankara University Faculty of Medicine Ankara 06620 Turkey Department of Pathology Ankara University Faculty of Medicine Ankara 06230 Turkey Ocular Oncology Service Wills Eye Hospital Thomas Jefferson University Philadelphia PA 19107 USA

AIM： To evaluate the clinical, radiological, and treatment features of lacrimal gland tumors.METHODS： Retrospective review of 99 eyes of 92 patients with lacrimal gland tumors diagnosed and managed in a single institution between January 1999 and March 2017. Clinical and radiological features, histopathology, treatment methods, and prognosis were evaluated.RESULTS： The mean patient age was 40.3（range： 7-80）y.The diagnosis was made histopathologically in 91（91.9%） tumors and on a clinical and radiological basis in 8（8.1%） tumors. Final diagnoses included idiopathic orbital inflammation（pseudotumor） in 46（46.5%） lesions, pleomorphic adenoma in 14（14.1%）, adenoid cystic carcinoma in 12（12.1%）, granulomatous inflammation in 10（10.1%）, lymphoma in 5（5.0%）, benign reactive lymphoid hyperplasia in 3（3.0%）, dacryops in 3（3.0%）, carcinoma ex pleomorphic adenoma in 2（2.0%）, adenocarcinoma in 1（1.0%）, dermoid cyst in 1（1.0%）, cavernous hemangioma in 1（1.0%）, and leukemic infiltration in 1（1.0%）. Nonepithelial tumors comprised 64.6%（n=64） of all lacrimal gland tumors, epithelial tumors 32.3%（n=32）, dermoid cyst 1%（n=1）, cavernous hemangioma 1%（n=1）, and leukemic infiltration 1%（n=1）. There were in total 78（78.8%） benign and 21（21.2%） malignant tumors. CONCLUSION： Overall, 65% of lacrimal gland tumors were of non-epithelial origin and 32% of epithelial origin. By histopathology and clinical evaluation, 79% of lacrimal gland tumors were benign. The most common lacrimal gland tumors include idiopathic orbital inflammation（46.5%）, epithelial（32.3%）, and lymphoproliferative（8.1%） lesions.

关键词： epithelial tumor inflammation lacrimal gland non-epithelial tumor orbit tumor

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Clinical Research on Benign Lymphoepithelial Lesions of lacrimal gland in 20 Chinese Patients

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Chinese Medical Journal 2015年第4期128卷 493-498页

作者： Jian-Min Ma Jing Li Xin Ge Ming Li Jin-Ru Li Xiao-Na Wang Beijing Tongren Eye Center Beijing Tongren Hospital Capital Medical University Beijing Ophthalmology and Visual Sciences Key Laboratory Beijing 100730 China Department of Pathology Beijing Tongren Hospital Capital Medical University Beijing 100730 China

Background：Benign lymphoepithelial lesion （BLEL） is characterized by symmetric bilateral swelling of the lacrimal and salivary glands and considered a subtype of immunoglobulin G4 （IgG4）-related sclerosing disease,the etiology and pathogenesis of which has not been determined.The purpose of the present study was to analyze the clinical features of BLEL in the lacrimal gland and the relationship between the serum level of IgG4 and BLEL.Methods：Twenty consecutive patients with BLEL diagnosed in Department of Ophthalmology at Beijing Tongren Hospital,Capital Medical University between January 2012 and December 2013 were observed.The clinical features,imaging findings,laboratory tests,treatments and follow-up status of these 20 consecutive patients were analyzed.Results：In all 20 patients,the ratio of male to female was 1：4,the ages ranged from 28 to 57 years,the ratio of unilateral to bilateral eyes involvement was 1：4,and painless uncongested symmetrical swelling of the upper eyelid was the main clinical manifestation.Orbital magnetic resonance imaging （MRI） showed that all patients involved lacrimal gland,which were obviously enlarged with equal signals in T1W images and T2W images and obvious enhancement on contrast MRI.Extraocular muscles were involved in 5 patients,salivary gland in 8 patients,and frontal nerve in 3 patients.Serum IgG4 concentration was elevated in 18 patients.The treatment strategy mainly included surgery and steroid administration.Three patients were lost to follow-up,17 patients reached complete response,and no recurrence was observed.Conclusions：Eyelid swelling is the typical symptom of BLEL.Most of the patients involved bilateral lacrimal glands.High serum IgG4 level and abundant IgG4-positive plasma cell infiltration are the important features,which can be found in most of BLEL patients.Surgery combined with glucocorticoids is an efficient treatment strategy.

关键词： Benign Lymphoepithelial Lesion Glucocorticoids Immunoglobulin G4 lacrimal gland Surgery

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Clinical analysis of 109 cases of lacrimal gland pleomorphic adenoma

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International Journal of Ophthalmology(English edition) 2021年第12期14卷 1852-1857页

作者： Rui Liu Nan Wang Hong Zhang Xin Ge Jian-Min Ma Beijing Tongren Eye Center Beijing Institute of OphthalmologyBeijing Tongren HospitalBeijing Ophthalmology&Vision Science Key LabCapital Medical UniversityBeijing 100730China

AIM:To monitor the prognosis of patients with lacrimal gland pleomorphic adenoma(LGPA)following surgical resection within the past 10y.The factors affecting patient prognosis are analyzed and the experience of surgical treatment is summarized.METHODS:In this retrospective,comparative case series,clinical records from 109 cases of LGPA treated chiefly at the same institution between November 2009 and May 2019 were reviewed.All 109 patients underwent surgery,histopathological examination,and imaging examination.For patients who underwent surgery for the first time,LGPA could be resected completely,including tumor and capsule tissues,using a surgical approach via the eyebrow arch or double eyelid crease.RESULTS:The ratio of males to females was 1:1.60,the ages ranged from 19 to 74 years old with a mean age of 43.64±13.07 years old,and the ratio of left to right eyes was 1:1.37.A total of 109 patients underwent surgical excision and five of these收稿日期radiotherapy after malignant transformation.Of these patients,15 were lost to follow up within the April 1,2020 deadline and 1 was diagnosed as a recurring pathology.The 5-year recurrence rate for 86 patients who underwent initial surgery was 7.27%.Single factor analysis revealed that the course of disease,bone destruction,invasion of surrounding tissues,tumor size,capsule integrity,and expression of Ki-67 were statistically significant(P<0.05).Binomial Logistic regression analysis showed that capsule integrity was a risk factor influencing recurrence(P=0.008).CONCLUSION:LGPA has a risk of recurrence and potential for malignant transformation.Complete removal of the tumor and capsule in the initial surgery is a key factor in preventing recurrence.

关键词： pleomorphic adenoma lacrimal gland malignant transformation treatment prognosis

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PPARγ: the dominant regulator among PPARs in dry eye lacrimal gland and diabetic lacrimal gland

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International Journal of Ophthalmology(English edition) 2020年第6期13卷 860-869页

作者： Peng-Yue Mu Chen-Chen Chu Di Yu Yan Shao Shao-Zhen Zhao Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science Eye Institute and School of OptometryTianjin Medical University Eye Hospital

AIM: To investigate the regulatory roles of the members of the peroxisome proliferator-activated receptor(PPAR)family in lacrimal gland dysfunction under conditions of desiccating stress or diabetes.METHODS: Quantitative polymerase chain reaction(qPCR) was used to examine the expression of PPARs in the cornea, conjunctiva, meibomian gland, and lacrimal gland in adult rats. The rats were divided into 3 groups:a control group, dry eye group, and diabetic group. The phenol red threads test, tear film break-up time(BUT) test and fluorescein staining were carried out to evaluate the development of dry eye. Based on bioinformatics research,qP CR was used to examine the expression level of PPARγ,tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β),interleukin-6(IL-6), sirtuin 1(Sirt1), myeloid differentiation factor 88(MyD88) and transforming growth factor-β(TGF-β)in the lacrimal glands.RESULTS: PPARα and PPARβ/δ were mainly expressed in the conjunctiva and the lacrimal gland, respectively.However, PPARγ was expressed in both the conjunctiva and lacrimal gland, at much higher levels than those measured for PPARα and PPARβ/δ. Dry eye rats and diabetic rats both showed decreased tear secretion, shortened BUT,and increased corneal staining. Significant changes in gene expression were observed compared with the control group. In the lacrimal glands of dry eye rats and diabetic rats, expression of PPARγ decreased(Placrimal glands. Down-regulation of PPARγ is highly relevant to lacrimal gland dysfunction under desiccating-stress and diabetic conditions. PPARγ, thus, is a potential therapeutic target in the treatment of environment-or diabetes-induced dry eye diseases.

关键词： dry eye diabetes PPARγ rat lacrimal gland

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Effects of extract of Buddleja officinalis on partial inflammation of lacrimal gland in castrated rabbits with dry eye

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International Journal of Ophthalmology(English edition) 2010年第2期3卷 114-119页

作者： Xiao-Lei Yao, Hui-An Zhu Department of Ophthalmology the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine Changsha 410007 Hunan Province China Medical School of Nanhua University Hengyang421001 Hunan Province China

AIMTo assess the effects of extract of Buddleja officinalis on tear secretion volume, tear film stability, expressions of TGF-β1, IL-1β, TNF-α in lacrimal gland of castrated rabbits with dry eye.

关键词： dry eye lacrimal gland extract of buddleja officinalis androgen

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Association of TCR-signaling pathway with the development of lacrimal gland benign lymphoepithelial lesions

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International Journal of Ophthalmology(English edition) 2015年第4期8卷 685-689页

作者： Jian-Min Ma Yi-Xin Cui Xin Ge Jing Li Jin-Ru Li Xiao-Na Wang Beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical University Beijing Ophthalmology &Vision Science Key Lab

·AIM: To identify the association of the T cell receptor(TCR) signaling with the development of benign lymphoepithelial lesions(BLEL) of the lacrimal gland.· METHODS: We collected affected lacrimal gland tissues from 9 patients who underwent dacryoadenectomy in the Capital Medical University Beijing Tongren Hospital Eye Center between August2010 and March 2013 and were confirmed to have lacrimal gland BLEL by histopathological analysis. Tumor tissues from 9 patients with orbital cavernous hemangioma were also collected and used as control.Whole genome gene expression microarray was used to compare gene expression profiles of affected lacrimal gland tissues from patients with lacrimal gland BLEL to those from of orbital cavernous hemangiomas.Differential expression of TCR pathway genes between these tissues was confirmed by polymerase chain reaction(PCR) and immunohistochemistry.·RESULTS: Microarray analysis showed that in lacrimal glands with BLEL, 32 signaling pathways were enriched in the upregulated genes, while 25 signaling pathways were enriched in the downregulated genes. In-depth analysis of the microarray data showed that the expression of 27 genes of the TCR signaling pathway increased significantly. To verify the differential expression of three of these genes, CD3, CD4, and interleukin(IL)-10, reverse transcription-PCR(RT-PCR)and immunohistochemistry assays were performed. RT-PCR analysis showed that CD3 and CD4 were expressed in the lacrimal glands with BLEL, but IL-10 was not expressed. Immunohistochemistry confirmed that CD3 and CD4 proteins were also present, but IL-10 protein was not. CD3, CD4, or IL-10 expression was not found in the orbital cavernous hemangiomas with either RT-PCR or immunohistochemistry.· CONCLUSION: TCR signaling pathway might be involved in the pathogenesis of lacrimal gland BLEL.

关键词： lacrimal gland benign lymphoepithelial lesion whole genome gene expression microarray T cell receptor-signaling pathway

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