Type 2 diabetes is a metabolic disease with increasing prevalence,which causes great socioeconomic burden.Intestinal flora is the microbiota located in the human intestines,which are participating in human growth and development,physiological procedures,or even pathogenesis as a closely connected environmental factor.There have recently been rapid progresses in the research on the relationship between intestinal flora and type 2 diabetes in the field of endocrinology and metabolism.In this article,we reviewed the overall framework and research progress in the relationship between intestinal flora and type 2 diabetes,aiming to shed some light on the future research about this topic.

OBJECTIVETo explore the role of CD4⁺ CD25⁺ Foxp3⁺ Treg/CD4⁺ IL-17A(+)Th17 cells and the related cytokines in Graves' ophthalmopathy.

METHODSBased on clinical activity scores (CAS), we divided patients with untreated Graves' ophthal- mopathy into active group (AGO group with CAS ≥ 3 (15 cases) and non-active group (NGO group) with CAS<3 (15 cases), with another 15 patients with untreated Graves' disease free of eye symptoms (GD group) and 15 normal subjects as controls. Peripheral venous blood Treg/Th17 cell ratio was determined using flow cytometry. RT-PCR was used to detect the mRNA expression levels of Treg-specific transcription factor Foxp3 and Th17-specific transcription factor RORγt. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of Th17 cell-related cytokines (IL-17A, IL-23, and IL-6) and Treg-related cytokines (TGF-β, IL-10, and IL-35).

RESULTSCompared with the normal subjects, the patients in GD, NGO, AGO groups all showed significantly increased Th17 cell count (P<0.05), which was the highest in AGO group. RT-PCR results revealed significantly increased RORγt in GD, NGO, and AGO groups, also the highest in AGO group. Serum IL-17A, IL-23, and IL-6 levels all showed significant increments in GD, NGO, and AGO groups (P<0.05), especially in AGO group. Among the Treg-related cytokines, TGF-β and IL-35 levels decreased (P<0.05) but IL-10 increased significantly (P<0.05) in GD, NGO, AGO groups.

CONCLUSIONDecreased immunosuppressive capacity of Treg cells can be an important factor in the pathogenesis of Graves' ophthalmopathy. Th17 cells may also participate in the occurrence and progression of Graves' ophthalmopathy and can serve along with related cytokines as novel indicators of the disease activity. Impaired Treg/Th17 balance may importantly contribute to the occurrence of Graves' ophthalmopathy.

Cytokines ; immunology ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Graves Ophthalmopathy ; immunology ; Humans ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

In December 2022, the European Thyroid Association(ETA) and American Thyroid Association(ATA) jointly released a consensus statement on the diagnosis and management of thyroid eye disease(TED). Taking into account the benefits and risks, the consensus provides specific recommendations for essential therapeutic agents. It also covers 34 key recommendations on the diagnosis and treatment decision-making, basic therapy and care, and risk factor control for TED.

The 2021 European Group on Graves′ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves′ Orbitopathy was released in July, 2021. Based on the 2016 version, the new guidelines updated the first-line management algorithm for patients with Graves′ orbitopathy in moderate-to-severe and active period, provided multiple second-line treatment pathways and made detailed recommendations from aspects of clinical assessment, general measures, and management of specific conditions, etc. At the same time, efficacy evaluation and management during COVID-19 period were explained in detail. The new guidelines also mentioned some novel treatment strategies of GO which still need further efficacy and safety verification.

Objective To investigate the quantitative value of the signal intensity ratio of extraocular muscle and ipsilateral white matter measured by MRI for the evaluation of activity in thyroid-associated ophthalmopathy. Methods A total of 129 patients and 245 eyeballs with thyroid-associated ophthalmopathy were enrolled in this study and this 245 eyeballs were set as thyroid-associated ophthalmopathy group(TAO group). There were 10 patients with newly diagnosed Graves'disease and in the same period and these 20 eyeballs were set as graves'disease group(GD group). 32 normal people from annual physical test excluded thyroid and eye diseases and their 64 eyes were selected randomly for the normal control group(NC group). The signal intensity of the extraocular muscle and the ipsilateral white matter on the MRI images were measured, while did exophthalmos and the width of the inner fat of eyeballs (FWs)measurements in the same time. Results SIR,FWs,and exophthalmos of TAO group were higher than those of the other 2 groups[SIRs:1.71(1.40,2.10)vs 1.26(1.22,1.34)and 1.23(1.14,1.32);FWs:8.04(6.70, 8.71)mm vs 6.16(4.86,7.08)mm and 6.93(6.41,7.65)mm,exophthalmos:20.10(18.56,22.15)mm vs 15.40(14.87,16.60)mm and 14.73(13.40,16.07)mm,all P<0.05]. The reference value of SIR establishing based on SIRs of NC group is less than 1.37. In total 129 TAO patients,55 patients(with 106 eyeballs)have a clinical activity score(CAS). Then,these eyeballs were grouped to activity and non-activity(grouped by CAS≥3),and the baseline group difference of these 2 groups was not statistically significant. The SIRs and exophthalmos of activity group were higher than the non-activity group[SIRs:1.70(1.45,2.33)vs 1.41(1.25,1.75); exophthalmos:(20.38 ± 2.40)mm vs(19.05 ± 3.70)mm,all P<0.05]. But the difference of FWs of these two groups was not statistically significant(P>0.05). The SIRs and CAS had a positive correlation(r=0.580,P=0.000),through the receiver operating characteristic curve(ROC)we get the best diagnostic performance of TAO activity when the SIR≥1.56(sensibility=65.6%,specificity=89.1%,AUC=0.815,P=0.000). Conclusion The signal intensity ratio of extraocular muscle and ipsilateral white matter may discriminate the activity of TAO early as a quantitative indicator, reflecting its efficacy,and is worth clinically generalizing.

Objective To evaluate life quality of Graves orbitopathy (GO) patients using Graves orbitopathy quality-of-life questionnaire (GO-QOL) and explore the influence factors of the quality of life of GO patients.Methods This was a cross-sectional study conducted at The Third Affiliated Hospital of Southern Medical University including 145 newly diagnosed GO patients.All the patient answered the GO-QOL and underwent ophthalmic and endocrine assessments.The main outcome measures were the scores on GO-QOL 2 subscales:visual functioning and appearance.Based on the classification in the guideline of European Group on Graves Orbitopathy (EUGOGO),the patients were divided into two groups:mild and moderate to severe groups.Then the scales between these two groups were compared and influencing factors were analyzed.Finally,the floor and ceiling effects were assessed.Results The GO-QOL scores for the subscales of visual functioning and appearance were 70.91±27.83 and 61.29±26.37 respectively in 145 GO patients.Visual functioning and appearance were lower in moderate to severe group (62.71 ±28.77 and 57.52 ± 26.49,respectively) than in mild group (85.58 ± 18.77 and 68.02 ±24.99,respectively).The GO-QOL scores for the visual functioning subscale were significantly correlated with age (P =0.002),clinical active score (P =0.011) and the degree of diplopia (P =0.00,R2=0.373).The GO-QOL scores for the appearance were significantly correlated with sex (P =0.05) and thyroid-stimulating hormone levels (P =0.001,R2 =0.231).No significant ceiling or floor effects were observed for either subscale of the GO-QOL.Conclusions With the aggravation of the disease,the quality of life of GO patients is getting worse and worse.The main influencing factors of the quality of life of GO patients include age,gender,diplopia,clinical active score and thyroid-stimulating hormone levels.Close attention needs to be paid to the quality of life of GO patients.

Objective:To quantify the fat of extraocular muscle in TAO patients with MRI fat-water separation technique.Methods:66 patients (129 eyes) with TAO were included in this study from November 2017 to July 2019. The age, gender, course of disease, disease activity and severity were collected. Fat fraction(FF) of the heaviest inflamed extraocular muscle was used as FFmax, the average FF of each orbital was recorded as FFmean. FF differences between groups of severity and activity were compared, the correlation between FF and clinical characteristics was also analyzed. Meanwhile, the changes of FF in follow-up patients before and after treatment were compared.Results:FFmean and FFmax of mild group were higher than moderate-to-severe as well as sight-threatening group. In male patients, active group′s FFmean and FFmax were lower. FF was different in groups which based on disease course ( P<0.05). Spearman correlation analysis showed a positive correlation between FF and disease course. Besides, there was a negative correlation between FF, disease activity, and disease severity ( P < 0.05). FF increased after treatment(FFmean: 34.03%±6.75% vs 32.26%±6.06%, P=0.040; FFmax: 33.43%±9.44% vs 29.04%±8.45%, P=0.006). Conclusion:MRI fat fraction can quickly and objectively quantify the fat of extraocular muscle, providing a new reference index for TAO′s disease evaluation.

Objective To explore the role of CD4+CD25+Foxp3+Treg/CD4+IL-17A+Th17 cells and the related cytokines in Graves' ophthalmopathy. Methods Based on clinical activity scores (CAS), we divided patients with untreated Graves' ophthal-mopathy into active group (AGO group with CAS≥3 (15 cases) and non-active group (NGO group) with CAS<3 (15 cases), with another 15 patients with untreated Graves' disease free of eye symptoms (GD group) and 15 normal subjects as controls. Peripheral venous blood Treg/Th17 cell ratio was determined using flow cytometry. RT-PCR was used to detect the mRNA expression levels of Treg-specific transcription factor Foxp3 and Th17-specific transcription factor RORγt. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of Th17 cell-related cytokines (IL-17A, IL-23, and IL-6) and Treg-related cytokines (TGF-β, IL-10, and IL-35). Results Compared with the normal subjects, the patients in GD, NGO, AGO groups all showed significantly increased Th17 cell count (P<0.05), which was the highest in AGO group. RT-PCR results revealed significantly increased RORγt in GD, NGO, and AGO groups, also the highest in AGO group. Serum IL-17A, IL-23, and IL-6 levels all showed significant increments in GD, NGO, and AGO groups (P<0.05), especially in AGO group. Among the Treg-related cytokines, TGF-βand IL-35 levels decreased (P<0.05) but IL-10 increased significantly (P<0.05) in GD, NGO, AGO groups. Conclusion Decreased immunosuppressive capacity of Treg cells can be an important factor in the pathogenesis of Graves' ophthalmopathy. Th17 cells may also participate in the occurrence and progression of Graves' ophthalmopathy and can serve along with related cytokines as novel indicators of the disease activity. Impaired Treg/Th17 balance may importantly contribute to the occurrence of Graves' ophthalmopathy.

Objective:To construct and test the reliability and validity of an assessment scale for self-management of patients with dry eye, so as to help patients establish dry eye related health behaviors.Methods:Based on the knowledge attitude and practice theory, the initial scale was constructed on the basis of literature review and qualitative interview, and revised through Delphi expert consultation and expert argumentation. After the preliminary investigation, 211 dry eye patients treated in the dry eye nursing outpatient department of Beijing Tongren Hospital from August 2023 to January 2024 were selected by convenience sampling method for questionnaire investigation to test the reliability and validity of the scale.Results:Among 211 dry eye patients, there were 58 males and 153 females, aged (39.31 ± 12.81) years old. The scale of self-management of patients with dry eye included 27 items in 3 dimensions: knowledge, attitude and behavior. The authority coefficient of the two rounds of expert consultation was 0.86, and the Kendall coordination index increased from 0.175 to 0.223 (both P < 0.01). The cumulative variance contribution rates of the three dimensions were 41.843%, 54.219% and 44.273%, respectively. The Cronbach α coefficient of the scale was 0.787, and the Spearman-Brown coefficient was 0.641. Conclusions:The scale of self-management of patients with dry eye has good reliability and validity and can be used in the assessment of dry eye patients to provide a reference basis for targeted guidance and intervention.

Objective To explore the role of CD4+CD25+Foxp3+Treg/CD4+IL-17A+Th17 cells and the related cytokines in Graves' ophthalmopathy. Methods Based on clinical activity scores (CAS), we divided patients with untreated Graves' ophthal-mopathy into active group (AGO group with CAS≥3 (15 cases) and non-active group (NGO group) with CAS<3 (15 cases), with another 15 patients with untreated Graves' disease free of eye symptoms (GD group) and 15 normal subjects as controls. Peripheral venous blood Treg/Th17 cell ratio was determined using flow cytometry. RT-PCR was used to detect the mRNA expression levels of Treg-specific transcription factor Foxp3 and Th17-specific transcription factor RORγt. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of Th17 cell-related cytokines (IL-17A, IL-23, and IL-6) and Treg-related cytokines (TGF-β, IL-10, and IL-35). Results Compared with the normal subjects, the patients in GD, NGO, AGO groups all showed significantly increased Th17 cell count (P<0.05), which was the highest in AGO group. RT-PCR results revealed significantly increased RORγt in GD, NGO, and AGO groups, also the highest in AGO group. Serum IL-17A, IL-23, and IL-6 levels all showed significant increments in GD, NGO, and AGO groups (P<0.05), especially in AGO group. Among the Treg-related cytokines, TGF-βand IL-35 levels decreased (P<0.05) but IL-10 increased significantly (P<0.05) in GD, NGO, AGO groups. Conclusion Decreased immunosuppressive capacity of Treg cells can be an important factor in the pathogenesis of Graves' ophthalmopathy. Th17 cells may also participate in the occurrence and progression of Graves' ophthalmopathy and can serve along with related cytokines as novel indicators of the disease activity. Impaired Treg/Th17 balance may importantly contribute to the occurrence of Graves' ophthalmopathy.