[Application of modified fusion convergence index in intermittent exotropia].

Objective: To investigate a modified fusional convergence parameter-total convergence amplitude/distance angle and its relationship with exotropia control, stereoacuity, and other visual functions in intermittent exotropia. Methods: The cross-sectional study included children diagnosed with intermittent exotropia at the First Affiliated Hospital of Nanjing Medical University from August 2020 to June 2021. A modification was made by combining total convergence amplitude using synoptophore and distance angle at distance using prism bars to calculate total convergence amplitude/distance angle. Exotropia control at distance and near measured by Office-based Scale for Assessing Control was classified as good control (scale 0-1) and poor control (scale 2-5). Statistical analysis was performed using Spearman correlation analysis, Mann-Whitney U test, Fisher's exact test, χ2 test, logistic regression analysis, and mediation effect analysis. Results: The study included 212 patients, of which 105 (49.5%) were male and 107 (50.5%) were female. The median (interquartile range) age was 9.0 (8.0, 10.0) years. Of 211 cases, 201 (94.8%) had binocular fusional function, while 11 cases (5.2%) did not have binocular fusional function. Among patients with binocular fusional function, inverse correlation was observed between total convergence amplitude and exotropia control scores for both distance (r=-0.427, P<0.001) and near (r=-0.194, P=0.006). Total convergence amplitude/distance angle was an independent predictive factor for exotropia control at distance (OR=0.195; 95%CI, 0.060-0.630; P=0.006) and near (OR=0.252; 95%CI, 0.085-0.746; P=0.013). Stereoacuity at distance (OR=3.110; 95%CI, 1.311-7.379; P=0.010) and near (OR=2.780; 95%CI, 1.401-5.517; P=0.003) were also factors associated with distance exotropia control. Mediation analysis revealed that stereoacuity was not a mediating factor between the ratio and distance control (distance: P=0.066; near: P=0.181). In patients with ratio≥1.5 °/PD, all the 15 patients demonstrated good control. On the contrary, patients with ratio<1.5 °/PD showed worse exotropia control (distance: P=0.001; near: P=0.040) and larger angles of deviation (distance: P<0.001; near: P<0.001). Conclusion: The modified fusional ratio, total convergence amplitude/distance angle, combining synoptophore and prism bars, could be used to evaluate the severity of intermittent exotropia. A higher ratio may be associated with poorer exotropia control. Though it may also be associated with distance exotropia control, stereoacuity is not the mediating factor between the modified ratio and distance exotropia control.

[Recommendations for the medication of rheumatic diseases in periconceptional period].

Rheumatic diseases are a kind of chronic inflammatory diseases mainly involving joints and surrounding tissues. Most patients with rheumatic diseases need long-term treatment, which is difficult to be avoided during pregnancy. Treatment efficacy, as well as maternal and fetal safety should be taken into account in the medical decision. Based on the domestic and foreign guidelines, consensus, diagnosis and treatment experience, Chinese Rheumatology Association developed the standardization of medication use in patients with rheumatic diseases preparing and during pregnancy, aiming on the application and precautions of commonly used medicines for rheumatic diseases in preparing pregnancy, pregnancy and lactation.

[Advances in epigenetic markers of dermatomyositis/polymyositis].

Idiopathic inflammatory myopathy (IIM) is a rare group of autoimmune diseases, characterized by chronic muscle weakness, muscle fatigue and infiltration of single nuclear cells in skeletal muscle. Its subtypes include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune-mediated necrotizing myositis (IMNM), and the most common subtypes are DM and PM. PM is an autoimmune disease mainly manifested by muscle damage. When the skin is involved, it is called DM. The incidence of IIM was relatively low, which was 1.16-19 per million people/year, but the mortality was high and the prognosis was poor. The pathogenesis of IIM is still unclear. Previous studies suggest that both immune and non-immune mechanisms are involved in its pathogenesis, especially cellular and humoral immunity. In recent years, researchers have conducted a number of studies on the pathogenesis of IIM, especially in the study of DM/PM with the application of high-throughput biometrics. Epigenetics is a discipline that refers to the genetic phenomena of DNA methylation spectrum, chromatin structure state and gene expression spectrum transferred between cells without any changes in DNA sequence, including DNA methylation, chromatin modification and non-coding RNA changes. A large number of studies have shown that epigenetic modification plays an important role in many diseases, especially in cancer. Recent studies have also found a series of epigenetic markers related to the occurrence and development of DM/PM, mainly in the aspect of non-coding RNA changes, such as miR-10a, miR-206, etc. And there has also been some research on DNA methylation. However, no studies have been reported on whether chromatin modification is involved in the pathogenesis of DM/PM. The pathogenesis of DM/PM is complex and diverse. With the development of research, certain microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) may become biological markers for the early diagnosis of DM/PM. Therefore, this paper mainly expounds the research progress of the biomarkers of DM/PM from the aspect of epigenetics.

[Altered serum cytokine expression profile in systemic sclerosis and its regulatory mechanisms].

OBJECTIVE: To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms. METHODS: Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1ß (IL-1ß), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein 1ß(MIP-1ß), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip. RESULTS: Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1ß, IL-1ra, IL-6, IP-10, MCP-1, TNF-α and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1ß and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1ß (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1ß TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated. CONCLUSION: There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation.

[The clinical characteristics, diagnosis and treatment of patients with gout in China].

Objective: To investigate the demographic characteristics, clinical features, diagnosis and treatment of patients with gout in China. Methods: Clinical data of 6 814 patients with gout from 100 hospitals in 27 provinces, municipalities or autonomous regions in China were collected and analyzed. Results: (1) The ratio of male to female in patients with gout was 14.7∶1. The mean age of onset was (48.8±15.1) years old. Mean serum urate level was (526.7±132.3) µmol/L. Patients' education background was of U-shaped distribution; (2) Hypertension was the most common comorbidity [15.8%(1 079/6 814)], then overweight or obesity [51.9%(3 536/6 814)]; (3) Alcohol and high-purine food intake were dominant triggering factors in men. The diagnosis of gout was made after onset in majority of patients with cardinal symptom arthralgia. Most patients had the disease less than 5 years, and the longer the course, the more flares in the previous year of entry; (4) Febuxostat was the mostly used urate-lowering medication. 20.7%(1 412/6 814), 10.8%(739/6 814) and 3.9%(265/6 814) of patients were followed up in 4 weeks, 12 weeks and 24 weeks after registration, and 18.9%(267/1 412), 29.1%(215/739) and 38.1%(101/265) of them reached the control target of serum urate levels, respectively. After treatment, patients' liver function was not affected, but serum creatinine levels decreased significantly. Conclusions: The proportion of gout patients who reach target serum urate level is very low. Further steps including education and survey need to be carried on.

[Immunometabolism and systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease, characterized by production of pathogenic autoantibodies and wide involvement of multiple systems. Damageofimmune tolerance and imbalance of immune homeostasis lead to the production of autoantibodies and the injuries of multiple organs and systems. In recent years, plenty of studies have identified that immunometabolism affects survival status of certain cells, also cell activation, differentiation and effector functions. Conversely, immune cells with different functions or differentiational status upregulate specific metabolic pathways to maintain their identities. In response to outer stimulations, naive immune cells differentiate into activated cells, accompanied with a series of immunometabolism changes. Therefore, abnormal immunometabolism can induce global imbalance of immune homeostasis, which further results in the initiation and development of autoimmune diseases, including SLE. Multiple abnormalities of immunometabolism have been found in patients with SLE or mouse models of lupus. Immune cells involved in the development of SLE, such as T cells, B cells, dendritic cells and macrophages present various metabolic abnormalities and pathological phenotypes. Among these cells, CD4+ T cells play predominant roles in the pathogenesis of SLE. Lots of studies demonstrated that CD4+ T cells and their subsets were in abnormal immunometabolic status,which further resulted in the development of SLE. In CD4+ T cells from patients with SLE or mouse models of lupus, both levels of glycolysis and oxidative phosphorylation are significantly higher compared with healthy controls. However,mitochondrial abnormalities, decreased ATP production and increased level of oxidative stress also have been found in these cells, which play important roles in the production of reactive oxygen intermediates and autoantibodies. Aggregated lipids rafts and increased synthesis of glycosphingolipid and cholesterol also have been observed in the CD4+ T cells from patients with SLE, leading to the abnormally elevated TCR signaling. Moreover, mechanistic target of rapamycin (mTOR) signaling is activated in the CD4+ T cells from both patients with SLE or mouse models of lupus and participate in the metabolic abnormalities of pathological CD4+ T cells. Progressive understanding of immunometabolism give us new insights of the pathogenesis of SLE and provide us with more therapeutic targets in the treatment of SLE.