Aseptic meningitis associated with primary Sj?gren′s syndrome: a case report / 中华神经科杂志

Sj?gren′s syndrome is a chronic autoimmune inflammatory disease characterized by exocrine gland and extraglandular involvement. Cases of Sj?gren′s syndrome-associated aseptic meningitis (SS-AM) are relatively rare, and a case of recurrent aseptic meningitis with leukopenia and mild anemia associated with primary Sj?gren′s syndrome is reported, whose symptoms basically disappeared after treatment with prednison and hydroxychloroquine. The purpose of reporting this case is to raise awareness of SS-AM among fellow clinicians.

Interleukin-12 participate in liver diseases of Sj?gren's syndrome through promoting oxidative stress / 中国免疫学杂志

Objective:To investigate the effect of interleukin-12(IL-12)on liver lesions and oxidative stress pathway in Sjo-gren's syndrome mice,and to clarify the possible mechanism of liver lesions in Sjogren's syndrome.Methods:Saliva flow rate,liver function,liver pathology and IL-12 level were measured in NOD,IL-12 knockout(IL-12KO)NOD and C57BL/6(B6)mice.Different concentrations of IL-12 and JAK2,TYK2 inhibitors were applied to mouse hepatoma cells.The oxidative stress index of mouse serum and cell culture supernatants of each group were determined.Results:Compared with the other two groups of mice,the NOD mice had significantly higher GOT and GPT(P<0.05),and decreased serum GSH-PX,SOD and CAT(P<0.05).CAT,GSH,GSH-PX and SOD were decreased,while MDA was increased in mice treated with different concentrations of IL-12.JAK2/TYK2 inhibitors reversed regulatory effects of IL-12 on SOD,GSH and MDA in hepatoma cells(P<0.05).Conclusion:IL-12 may aggravated liver damage of Sj?gren's syndrome through promoting oxidative stress of hepatocytes.

Analysis of Key Genes and Immune Infiltration Mechanism of Primary Sj?gren's Syndrome and Prediction of Targeted Traditional Chinese Medicine Based on Bioinformatics / 世界科学技术-中医药现代化

Objective Using bioinformatics methods to study the immune infiltration mechanism of Primary Sj?gren's syndrome(pSS)and to explore potential target Chinese medicines,which can provide new directions for the clinical treatment of pSS.Methods Gene expression profile microarray dataset of pSS was downloaded from the GEO database,differential genes were screened using R software,and gene ontology(GO)and gene pathway enrichment(KEGG)enrichment analysis was performed on these differential genes.Protein interaction network analysis of differential genes was performed by applying the STRING database,key genes were screened by using Cytoscape,and ELISA for the verification of key genes expression.Immune infiltration and correlation of immune cells in pSS were calculated by CIBERSORT inverse convolution method in 22.Finally,the herbal prediction of key target genes was performed by using the Coremine Medical database.Results A total of 232 differential genes were obtained,of which 207 were up-regulated and 25 were down-regulated.GO was mainly enriched in:leukocyte mediated immunity,lymphocyte mediated immunity,leukocyte cell-cell adhesion,etc;KEGG was mainly enriched in Hematopoietic cell lineage,Primary immunodeficiency,Intestinal immune network for IgA production,Phagosome,Leishmaniasis.Ten key genes were screened:PTPRC,CD19,LCP2,CCR5 and CD69 etc.The hub genes expression in the pSS is the same as that of GSE40611.Immune infiltration showed that memory B cells,T cells CD4 memory activated,and T cells CD4 na?ve were highly expressed in the pSS.Immune cell correlation analysis showed a positive correlation between initial Monocytes and T cells regulatory(Tregs),a positive correlation between Macrophages M1 and B cell na?ve,and a negative correlation between Plasma cells and T cells CD4 memory activated.COREMINE Medical predicted that Ginseng,Panax notoginseng,Tripterygium wilfordii,Burnet,Magnolia,and Strychni may treat pSS.Conclusion The development and progression of pSS are the results of the combined involvement of multiple genes and pathways.Memory B cells,T cells CD4 memory activated,and T cells CD4 na?ve may promote the development of pSS.The predicted Ginseng,Panax notoginseng,Tripterygium wilfordii,Burnet,Magnolia,Strychni may be used as target herbs for the potential treatment of pSS.

Clinical characteristics and the progress of classification criteria for children with Sj?gren′s syndrome / 中华实用儿科临床杂志

Sj?gren′s syndrome(SS) is a chronic inflammatory autoimmune disease, including primary SS (pSS) and secondary SS (sSS). Pediatric sSS has the similar clinical characters with pSS, which can be classified based on the same classification criteria.Compared with those of adult SS, pediatric SS is rare, insidious and lacks the typical manifestations of dry eyes and dry mouth.Therefore, the classification criteria for adult SS is not suitable for pediatric SS.So far, there are no classification criteria for pediatric SS that have been widely applied and validated, which needs to be further explored.The present review described the clinical characteristics and progress of classification criteria for pediatric SS, and compared pSS and sSS in affected children.

Analysis of associated factors and construction of prediction model for primary Sj?gren′s syndrome complicated with renal damage / 中华风湿病学杂志

Objective:To investigate the key factors of renal damage in patients with primary Sj?gren′s syndrome (pSS), to construct a risk prediction model.Methods:Clinical data of 419 pSS inpatients in the Nanjing Drum Tower Hospital from 2017 to 2020 were retrospectively analyzed. The patients were randomly divided into the model group (315 cases) and the validation group (104 cases) in a 3∶1 ratio by R software randomized package. T test was used in accordance with the normal measurement data, Chi square test was used for counting data, and Kruskal-Wallis H and Mann-Whitney U test were used for non-normal distributed data. A nomogram model was created based on independent factors of renal damage by using LASSO Cox regression analysis, and the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were applied to evaluate the sensitivity, accuracy and clinical practicability of the model. Results:Renal impairment occurred in 127 (30.3%)pSS patients, including 89 (70.1%) cases with renal insufficiency, 86 cases with hematuria (67.7%), 107 cases with proteinuria (84.2%) and 49 cases with renal tubular acidosis. Compared with those without renal damage, patients with renal damage had a longer course of disease [3.00 (1.00, 8.00) years vs 1.00 (0.30, 5.00) years; Z=2.33, P=0.005], presence of fatigue [35.1% (33/94) vs 23.5% (52/221), Z=4.49, P=0.038], decreased blood cells count [white blood cell 4.50(3.30, 6.75)×10 9/L vs 5.40(3.70, 8.05)×10 9/L, Z=2.02, P=0.043; hemoglobin 99.00(79.00, 111.00)g/L vs 120.00 (109.00, 128.00)g/L, Z=6.59, P<0.001; platelet 152.00 (89.25, 204.25)×10 9/L vs 188.00 (117.99, 241.00)×10 9/L, Z=2.61, P=0.009], stronger inflammatory reactions [ESR 48.50 (29.75, 86.25)mm/1 h vs 26.00 (11.00, 52.00)mm/1 h, Z=5.83, P<0.001; CRP 5.80 (3.40, 18.45)mg/L vs 4.40 (2.60, 11.40) mg/L, Z=2.33, P=0.020] and higher positive rate for anti-SSA/B antibodies [79.79%(75/94) vs 61.99%(137/221), χ2=9.49, P=0.002; 37.23%(35/94) vs 18.10%(40/221), χ2=13.31, P<0.001], but relatively less pulmonary involvement [20.2%(19/94) vs 33.9%(75/221), χ2=5.93, P=0.016], the differences were statistically significant ( P<0.05). Lasso binary logistics regression analysis showed that EULAR Sj?gren′s syndrome disease activity index score >9[ OR(95% CI)=9.019(3.294, 24.689), P<0.001], dry eye[ OR(95% CI)=2.853(1.502, 5.422), P=0.011], anemia[ OR(95% CI)=3.819(1.913, 7.626), P<0.001], low complement C3 level[ OR(95% CI)=2.453(1.233, 4.879), P=0.011]and hypoalbuminemia [ OR(95% CI) =6.898 (3.007, 15.821), P<0.001] as well as C-reactive protein [ OR (95% CI)=2.168 (1.136, 4.139), P=0.019] were significant related factors of renal impairment. The AUC (95% CI) of the prediction group and the validation group were 0.851 (0.806, 0.896) and 0.832 (0.742, 0.922), respectively, and the model plot and DCA showed that the model had good specificity and clinical efficacy. Conclusion:We propose a new nomogram model with good differentiation and calibration to assist in clinical screening of renal damage in pSS.

The clinical significance of CX3CL1 in primary Sj?gren′s syndrome complicated with interstitial lung disease / 中华风湿病学杂志

Objective:To investigate the clinical significance of CX3CL1 in pSS-ILD.Methods:A total of 103 pSS patients treated in the Department of Rheumatology and Immunology of the Affiliated Hospital of Guilin Medical College from December 2019 to December 2020 were included (42 cases with ILD and 61 cases without ILD), and 46 healthy physical check-up subjects in the health check-up center of the Affiliated Hospital of Guilin Medical college were included as controls. Demographic data, clinical manifestations, clinical parameters, lung function test, lung HRCT and serum samples of enrolled patients were collected. The serum levels of CX3CL1 and KL-6 in PSS-ILD patients, pSS patients and healthy subjects were detected by ELISA, and the correlation between CX3CL1 and clinical related indexes in pSS-ILD and pSS patients was analyzed. Independent sample t test, Kruskal-Wallis H test, Pearson correlation and Logistic regression analysis were used for statistical analysis. Results:As KL-6, the levels of CX3CL1 were significantly higher in the pSS-ILD group compared to both the pSS and control groups [CX3CL1: 9.08 (3.97, 30.56)ng/ml, 8.12 (6.16, 8.89)ng/ml, and 7.09 (5.86, 9.07)ng/ml, H=3.53, P=0.019; KL-6: 19.08 (8.05, 24.72)mU/ml, 15.9 (4.52, 19.26)mU/ml, 12.74 (8.09, 16.23) mU/ml, H=9.85, P=0.008]. Furthermore, CX3CL1 was shown to be positively correlated with KL-6( r=0.82, P<0.001). The cutoff value for CX3CL1 was determined to be at a concentration of 9.07 ng/ml with a specificity of 86.9% and sensitivity of 43.6%. The area under the receiver operating characteristic curve was 0.603. CX3CL1 exhibited significant correlations with predcited carbon monoxide dispersion as a percentage of expected value ( r=-0.45, P=0.004), HRCT score ( r=0.54, P<0.001), pulmonary hypertension ( r=0.37, P=0.039), ESSDAI score ( r=0.36, P=0.049), as well as chest tightness and acute breath (coefficient of association r=0.49, P<0.001). Conclusion:The level of serum CX3CL1 is directly proportionate to the severity of KL-6, pulmonary fibrosis, and lung function impairment, thereby suggests that CX3CL1 can be utilized as a parameter for the diagnosis and assessment of pSS-ILD.

The role of IL-17A in the pathogenesis of primary Sj?gren′s syndrome / 中华风湿病学杂志

Objective:To investigate the role of IL-17A in the regulation of inflammatory factors and autophagy genes of PBMCs in pSS patients.Methods:Thirty patients fulfilled the diagnosis of pSS were selected, 20 mL of peripheral blood was drawn, PBMCs were isolated and divided into the PBMCs group, IL-17A stimulant group and IL-17A inhibitor group. After warm incubation 48 h of immunofluorescence was applied to detect microtubule-associated protein l light chain 3 (LC3), and the ELISA method was used to detect the expression of the inflammatory factors IL-4, IFN-γ, IL-13 expression. Real-time fluorescence polymerase chain reaction (qRT-PCR) was used to detect the expression of autophagy-inducing genes Ambra-1, Bif-1 and apoptosis genes Bcl-2 and Bcl-XL mRNA, and immunoprotein blotting was used to detect the expression of Beclin1 and LC3 protein. ANOVA was used to compare the differences between groups, and t-test was used for two-by-two comparisons. Results:The immunofluorescence results showed a significant increase in LC3 autophagic vesicles in the IL-17A inhibited group compared with the IL-17A stimulator group. The ELISA results showed that, compared with the PBMCs group [IL-4: (13.39±0.32) pg/ml, IFN-γ: (14.4±0.4) pg/ml, and IL-13: (854±36) pg/ml], IL-4 secretion in the IL-17A stimulated group (11.54±0.30) was decreased ( t=12.83, P=0.024), IFN-γ and IL-13 secretion [(17.6±0.4), (908±51) pg/ml] were increased ( t=19.35, P=0.033; t=2.55, P=0.020); compared with IL-17A inhibitor group [IL-4: (15.65±0.26) pg/ml, IFN-γ: (13.6±0.3) pg/ml, and IL-13: (792±57) pg/ml]. Compared with the IL-17A stimulator group, IL-4 secretion was decreased ( t=21.31, P=0.006), and IFN-γ and IL-13 expression was increased ( t=17.34, P=0.015; t=5.14, P=0.007). The PCR results showed that, compared with Ambra-1, Bif-1, Bcl-2, and Bcl-XL mRNA expression (5.61±0.33, 5.04±0.60, 1.28±0.09, 1.56±0.03) in the PBMCs group, Ambra-1, Bif-1 mRNA in the IL-17A-stimulated group expression (3.76±0.24, 4.68±0.41) were down-regulated ( t=14.30, P=0.007; t=15.02, P=0.012), and Ambra-1, Bif-1 mRNA expression (7.91±1.17, 9.30±0.25) were increased in the IL-17A inhibition group, ( t=13.59, P=0.025; t=11.54, P=0.031), anti-apoptotic proteins Bcl-2, Bcl-XL mRNA expression (1.75±0.06, 2.43±0.16) was up-regulated in IL-17A stimulated group ( t=19.92, P=0.006; t=21.04, P=0.007) were up-regulated and Bcl-2, Bcl-XL mRNA expression (0.48±0.03, 0.83±0.10) were down-regulated in the IL-17A inhibition group ( t=29.44, P=0.027; t=16.31, P=0.023). The results of protein blotting assay showed that, Beclin-1 and LC3 protein expression (0.51±0.10, 0.559±0.010) were decreased in IL-17A stimulated group compared with Beclin-1, LC3 protein expression (0.72±0.09, 0.635±0.017) in PBMCs group ( t=14.38, P=0.034; t=17.99, P=0.014); BecLin-1 and LC3 protein expression (0.83±0.11, 0.737±0.025) increased in the IL-17A inhibition group ( t=9.72, P=0.027; t=22.35, P=0.007). Conclusion:IL-17A plays a role in pSS by regulating the expression of inflammatory factors IL-4, IFN-γ, IL-13 and autophagy related genes Beclin1 and LC3.

Clinical features of patients with connective tissue disease combined with sarcoidosis / 中华风湿病学杂志

Objective:To investigate the clinical features of patients with coexisting connective tissue disease (CTD) and sarcoisosis and to avoid misdiagnosis and mistreatment.Methods:To analyze the clinical manifestations, laboratory data, imaging and pathological features of patients with CTD combined with sarcoidosis in Peking Union Medical College Hospital from January 1985 to December 2021.Results:There were 17 patients with CTD(including 10 SS, 2 DM, 2 PBC, 1 SLE, 1 RA and 1 UCTD), combined with sarcoidosis, with a mean age of (55±10) years old and the ratio of male-to-female was 1:16. Eight patients were diagnosed as CTD before sarcoidosis, while 3 patients after sarcoidosis. The other 6 patients were diagnosed with the two diseases almost simultaneously. Lymphadenopathy(12/17), pulmonary nodules (8/17), subcutaneous nodules (4/17), rash (4/17) and blurred vision (1/17) were the main manifestations of patients with the onset of nodular disease. Nine patients were treated based on the presentation of sardoisis and 5 patients for CTD; 3 patients were treated for both diseases at the same time. All 17 patients discharged with improvement after treatment.Conclusion:When sarcoidosis do coexists with CTD, occult CTD might occur. It is important to investigate specific manifestations including pathological features of sarcoidosis and differentiate it from CTD.

Recommendations for the diagnosis and treatment of Sj?gren′s syndrome in China / 中华内科杂志

Sj?gren′s syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocyte proliferation and progressive exocrine gland damage. In addition to the impairment of salivary and lacrimal gland function, SS can present with multi-system and multi-organ involvement, accompanied by autoantibodies in serum and hyperimmunoglobulinemia. SS can be divided into primary and secondary forms based on the absence or presence, respectively, of concurrent connective tissue diseases such as systemic lupus erythematosus and rheumatoid arthritis. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association drafted standardized criteria for the diagnosis and treatment of primary SS. The objectives were to standardize the detection and interpretation of key indicators for the diagnosis of SS, including serum anti-SSA antibody and labial gland pathology, suggest the use of the widely accepted European League Against Rheumatism (EULAR)-SS disease activity index for the evaluation of the disease, and standardize the rational management of SS patients with topical and systemic therapies.

Clinical characteristics of patients with rheumatic diseases and abnormal liver function / 中华内科杂志

Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

Inflammatory pathogenesis of Primary Sj?gren's syndrome / 中国免疫学杂志

Primary Sj?gren's syndrome(pSS)is a chronic inflammatory autoimmune disease involving a variety of exocrine glands.It is a common autoimmune disease in the department of rheumatology.However,the pathogenesis of pSS is still unclear,re-sulting in lack of treatment.While the international research on pSS is also increasing,we review the latest literature on the mecha-nism of Sj?gren's syndrome under different factors.In this paper,the process mechanism of Sj?gren's syndrome is summarized from the aspects of heredity,environment,autoimmune cells and autoantibodies.

Recent advance of Marinesco-Sj?gren syndrome / 中华神经医学杂志

Marinesco-Sj?gren syndrome (MSS), also known as hereditary ataxia-dwarf-mental retardation syndrome, is a rare autosomal recessive ataxia syndrome. This article reviews the recent advance in clinic characteristics, pathogenic gene mutation sites, pathogenesis and clinic diagnosis and treatment of MSS, in order to improve clinicians' understanding of the disease and diagnosis and treatment level, and reduce the missed diagnosis and misdiagnosis of the disease.

Quality of sleep in patients with primary Sj?gren′s syndrome and its influence on clinical features / 中华风湿病学杂志

Objective:To investigate the quality of sleep in primary Sj?gren′s syndrome (pSS) patients and its impact on clinical features.Methods:One hundred patients with pSS who were hospitalized in the Department of Rheumatology of the Second Hospital of Shanxi Medical University from January 2019 to April 2021 were included into this study. Pittsburgh sleep quality index (PSQI), fatigue severity score (FSS), Euro QOL five dimensions questionnaire (EQ-5D), beck depression inventory second edition (BDⅠ-Ⅱ) and visual analog scale (VAS) were used to assess patients' symptoms and overall condition. The data was statistically managed and compared by χ2 test, independent sample t test, Mann-Whitney U test, and Logistic regression. Results:The prevalence of sleep disorders in pSS patients was 42.0%(42/100). The prevalence of sleep disturbance in pSS patients without depression was 28.8%(17/59). The EQ-5D[0.66(0.59, 0.76)] and Eur-opean league against rheumatism Sj?gren's syndrome disease activity index (ESSDAI) scores [1.0(0.0, 3.0)] were lower in patients in the sleep-disordered group than in those [0.76(0.71, 1.20) and 2.5(1.0, 4.0)] who slept well [ Z=3.07, P=0.012; Z=3.18, P=0.011], respectively. The European league against rheumatism Sj?gren's syndrome patients report index (ESSPRI) scores [6.2(4.8, 7.9)], VAS levels in overall dry eyes [60.0(21.4, 82.1)], anxiety [11.0(2.9, 43.0)], overall physician global assessment (PGA) [46.0(18.0, 65.0)], fatigue severity scale (FSS) [4.34(3.01, 5.61)], and BDⅠ-Ⅱ [15.1(7.3, 22.4)] in patients with sleep disorder were higher than those [4.1(2.8, 5.3), 40.0(7.0, 70.3), 2.3(0.0, 18.0), 11.0(0.0, 52.0), 2.45(1.65, 4.40), and 7.4(4.3, 12.8)] of the normal sleep group [ Z=2.03, P=0.043; Z=2.04, P=0.042; Z=2.19, P=0.031; Z=3.00, P=0.015; Z=3.43, P=0.001; Z=3.12, P=0.003]. The sleep-disordered group had higher levels of lymphocyte count (2.0±1.5)×10 9/L and erythrocyte sedimentation rate (ESR) (46±20) mm/1 h respectively when compared with (1.4±1.3)×10 9/L and (38±17) mm/1 h in the good sleep group ( t=2.00, P=0.048; t=2.04, P=0.044). PSQI scores were negatively correlated with immunoglobulin (Ig)G ( r=-0.20, P=0.012) and ESSDAI ( r=-0.26, P=0.004), while positively correlated with FSS( r=0.38, P=0.001), BDⅠ~Ⅱ ( r=0.47, P=0.014), ESSPRI ( r=0.46, P=0.001), white blood cell count ( r=0.28, P=0.013) or neutrophil count ( r=0.26, P=0.009). The results of multifactorial analysis suggested that leukocytopenia [ OR(95% CI)=0.245(0.065, 0.692), P=0.005] was one of the risk factors for sleep disorders. Conclusion:Sleep disorders in pSS patients affects the patients' disease prognosis and activity index by affecting the patients' somatic symptoms, psychological profile and immune function. Active clinical multidis-ciplinary interventions for pSS patients are necessary, not only for better assisting physicians in the manage-ment of chronic diseases, but also for better help patients recovery of their physical and mental health.

Immunoregulatory effects of miR-31-5p overexpression on peripheral blood Th17 cell in a rabbit model of autoimmune dry eye / 中华实验眼科杂志

Objective:To investigate the immunoregulatory effects of lentivirus-mediated microRNA (miR)-31-5p overexpression on peripheral blood T helper cell 17 (Th17) in a rabbit model of autoimmune dry eye.Methods:The miR-31-5p recombinant lentiviral vector was constructed.Lentivirus overexpressing miR-31-5p and its control virus were packaged.The concentration measurement and lentiviral titer determination were carried out.A rabbit model of autoimmune dry eye was established and the peripheral blood mononuclear cells (PBMC) of the rabbits were isolated.PBMC infected with miR-31-5p and negative control lentivirus particles were assigned as the miR-31-5p overexpression group and control group, respectively.The miR-31-5p expression level was detected using quantitative real-time PCR (qRT-PCR). Then PBMC in the two groups were co-cultured with γ-ray irradiated lacrimal gland epithelial cells.The expressions of Th17 cell related transcription factor retinoic acid-receptor-related orphan receptor C (RORC) and interleukin-17 (IL-17) mRNA, IL-1β, IL-6 and IL-23 were determined by qRT-PCR.The IL-17 protein expression level was detected by Western blot.The use and care of animals complied with Regulation for the Administration of Affair Concerning Experiment Animals by State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.TJYY20201221036).Results:The construction of the miR-31-5p recombinant lentiviral vector was verified by DNA sequencing.The lentiviral titer of lentivirus overexpressing miR-31-5p and control lentivirus particles was 3.82×10 7 TU/ml and 3.50×10 7 TU/ml, respectively.The miR-31-5p relative expression level of PBMC was significantly increased in miR-31-5p overexpression group in comparison with control group, showing a statistically significant difference ( t=-9.696, P<0.001). When PBMC were co-cultured with lacrimal gland epithelial cells in vitro, the relative expression levels of RORC and IL-17 mRNA in miR-31-5p overexpression group were 0.33±0.03 and 0.28±0.09, which were significantly decreased in comparison with 1.00±0.00 and 1.00±0.00 in control group, with statistically significant differences between them ( t=46.256, 13.810; both at P<0.05). The relative expression level of IL-17 protein in miR-31-5p overexpression group was significantly reduced than control group ( t=4.977, P=0.008). The relative expression levels of IL-1β, IL-6 and IL-23 mRNA were significantly lower in miR-31-5p overexpression group than control group ( t=220.076, 6.641, 13.271; all at P<0.05). Conclusions:The overexpression of miR-31-5p can inhibit the Th17-immune response via down-regulating the expression of IL-6, IL-1β and IL-23.

The clinical value of shear wave elastography and salivary gland ultrasound scoring in salivary gland lesions of Sj?gren′s syndrome / 中华超声影像学杂志

Objective:To evaluate the value of shear wave elastography (SWE) and salivary gland ultrasound scoring(SGUS) system in the diagnosis of salivary glands lesions in patients with Sj?gren′s syndrome(SS) and to compare the diagnostic efficiency of the two methods.Methods:From June 2019 to November 2020, Fifty-eight patients with suspected SS were selected from the Affiliated Changzhou No.2 People′s Hospital of Nanjing Medical University. According to the 2002 American-European Consensus Group classification standard, the enrolled patients were divided into two groups: SS group (47 cases) and non-SS group(11 cases). According to symptom duration, SS group was divided into the ≤5 years group (29 cases) and the >5 years group (18 cases). Meanwhile, 40 healthy volunteers were enrolled in this study as normal control group. The diagnostic value of salivary gland ultrasound scoring system and Young′s modulus in SS were analyzed.Results:The differences in Young′s modulus of parotid gland and submandibular gland between SS group and non-SS group (or control group) were statistically significant (all P<0.05). The ultrasound score of SS group was significantly higher than that of non-SS group and control group (all P<0.05). SGUS and Young′s modulus were not significantly different between different course groups (all P>0.05). The areas under ROC curve of the mean Young′s value in parotid and submandibular gland and the SGUS were 0.801, 0.829 and 0.676, respectively. The comparison of the area under the curve between the Young′s modulus of the parotid and submandibular glands and the ultrasound score was statistically significant (all P<0.05). Conclusions:SWE and Ultrasonography scoring system have certain value in the diagnosis of salivary gland lesions in SS, and can provide important reference information for clinical diagnosis from different perspectives. The diagnostic efficiency of SWE for salivary glands lesions in patients with SS is better than that of SGUS scoring system.

Difference in clinical characteristics of patients with primary Sj?gren's syndrome by gender and age of disease onset / 中华风湿病学杂志

Objective:To compare the clinical characteristics of patients with primary Sj?gren's syndrome (pSS) by gender and age of disease onset.Methods:Clinical data of hospitalized patients with pSS in China-Japan Friendship Hospital from March 2014 to August 2020 were retrospectively analyzed. Patients were divided into different groups according to their genders and ages of disease onset (young grong <30 years, middle-age group 30-59 years, elderly group ≥60 years). Chi-square test and Mann-Whitney U test were used to compare data in subgroups, and logistic regression was performed to analyze data after control covariates. Results:Five hundred and forty one patients with pSS were included in this study and 481 of them were women (88.9%) Women had higher ratio than men in dry mouth [ OR (95% CI) =2.172(1.091, 4.323), P=0.027], dry eyes [ OR(95% CI)=2.179(1.062, 4.469), P=0.034], leukocytopenia [ OR(95% CI)=3.789(1.150, 12.482), P=0.029], ANA titer≥1∶160 [ OR(95% CI)=2.233(1.279, 3.898), P<0.01], positive anti-SSA [ OR(95% CI)=2.919(1.644, 5.183), P<0.01], positive anti-Ro52 [ OR(95% CI)=3.018(1.685, 5.405), P<0.01], while men had higher ratio than women in parotid enlargement [ OR(95% CI)=2.345(1.281, 4.325), P<0.01], and interstitial lung disease (ILD) [ OR(95% CI)=2.593(1.460, 4.606), P<0.01]. Compared with patients in young group, patients in middles age group had higher ratio in dental caries [ OR(95% CI)=5.940(2.230, 15.819), P<0.01], xero-phthalmia [ OR(95% CI)=2.904(1.313, 6.425), P<0.01], arthralgia [ OR(95% CI)=1.959(1.039, 3.694), P=0.038] and ILD [ OR(95% CI)=2.247(1.018, 4.959), P=0.045], but lower ratio in renal involvement [ OR(95% CI)=0.402(0.211, 0.766), P<0.01]; patients in elderly group had higher ratio in dental caries [ OR(95% CI)=7.437(2.441, 22.656), P<0.01], xerophthalmia [ OR(95% CI)=6.084(1.901, 19.468), P<0.01], and ILD [ OR(95% CI)=4.857(2.029,11.627), P<0.01]. Compared with patients in elderly group, patients in young group had higher positive rate in anti-SSA [ OR(95% CI)=2.836(1.245, 6.459), P=0.013], anti-SSB [ OR(95% CI)=3.075(1.413, 6.690), P<0.01], rheumatoid factors (RF) [ OR(95% CI)=3.323(1.620, 6.817), P<0.01] and elevated immunoglobulin G (IgG)[ OR(95% CI)=3.567(1.747, 7.284), P<0.01]; patients in middle age group had higher positive rate in anti-SSB[ OR(95% CI)=2.330(1.315, 4.130), P<0.01], RF [ OR(95% CI)=2.026(1.279, 3.208), P<0.01], and elevated IgG [ OR(95% CI)=2.077(1.297, 3.327), P<0.01]. Conclusion:Women with pSS present a higher ratio in dry mouth, dry eyes, leukocytopenia and positive autoantibodies than men, while parotid enlargement and ILD are more common in men than women. Young patients are prone to renal involvement, middle-aged patients are prone to arthralgia, while elderly patients are prone to dental caries and xerophthalmia. With the growth of age, the positive rates of autoantibodies and elevated IgG are decreased gradually in patients with pSS, but the ratios of dental caries, xerophthalmia and ILD is increased gradually.

The value of multi-echo Dixon technique and T 2 mapping for evaluating early parotid gland changes in primary Sj?gren′s syndrome / 中华放射学杂志

Objective:To assess the value of the parotid fat fraction (FF) and T 2 relaxation time (T 2 value) in the evaluation of early parotid involvment in patients with primary Sj?gren′s syndrome (pSS) using multi-echo Dixon technique and T 2 mapping imaging. Methods:From December 2018 to December 2019, 26 early pSS patients (pSS group) and 20 healthy controls (control group), matched to age and gender, were enrolled at the First Affiliated Hospital of Zhengzhou University in this prospectively study. All subjects underwent conventional MRI, DWI, multi-echo Dixon and T 2 mapping sequences before treatment. The ADC, FF and T 2 value of bilateral parotid parenchyma in pSS group and control group were measured respectively. Paired sample t test was used to compare the differences of ADC, FF and T 2 values between left and right parotid glands for pSS group and control group, while independent sample t test was used to compare the differences of ADC, FF and T 2 values between pSS group and control group. The ROC curves were drawn to evaluate diagnostic performance of ADC, FF and T 2 values to distinguish early pSS, and the difference of diagnostic efficacy of each parameter was compared by Delong test. Binary logistic regression analysis and ROC curve were used to evaluate the diagnostic performance of the combination of the 3 parameters in early pSS. Results:There were no significant differences of ADC, FF and T 2 values between left and right parotid glands for pSS group and control group (all P>0.05). The parotid ADC values were significantly lower in pSS group than control group ( t=4.641, P=0.006), while the FF and T 2 values of pSS group were significantly higher than those of control group ( t=-2.910, -6.411, both P<0.001). The areas under the ROC curve of ADC, FF and T 2 values to distinguish early pSS were 0.666, 0.750 and 0.862, respectively. The area under ROC curve of the combination of ADC, FF and T 2 values was 0.930, with a sensitivity of 73.1% and a specificity of 97.5%. T 2 values showed a better diagnostic efficacy than ADC values ( Z=2.626, P=0.009) and FF values ( Z=2.112, P=0.035) when distinguishing pSS group from control group. The area under ROC curve of the combination of ADC, FF and T 2 values showed a better diagnostic efficacy than each parameter alone ( Z=4.869, P<0.001, Z=3.628, P<0.001, Z=2.162, P=0.031). Conclusions:Multi-echo Dixon technique and T 2 mapping can quantitatively evaluate the parotid gland fat deposition and inflammatory response in the early stage of pSS. T 2 value has great potential in evaluating early parotid gland injury of pSS, and the combination of ADC, FF and T 2 values can further improve the diagnostic efficiency.

Primary Sj?gren syndrome complicated with lymphoma: a report of 10 cases with literature review / 中华全科医师杂志

Clinical characteristics, treatments and prognosis of 10 primary Sj?gren syndrome (pSS) patients with lymphoma were retrospectively analyzed. All 10 patients were female. Dry mouth, dry eyes and lymph node enlargement were common. Laboratory tests showed positive antinuclear antibody(ANA), anti-SSA antibody, anti-SSB antibody and rheumatoid factor(RF); lower lymphocyte counts and high IgG level. All patients were not treated regularly after pSS was diagnosed; 9 cases of non-Hodgkin lymphoma (NHL) and 1 case of Hodgkin lymphoma (HL) were finally diagnosed. The main histological types of NHL were mucosa-associated lymphoid tissue marginal zone lymphoma (MALT) and diffuse large B cell lymphoma (DLBCL). Both intranodal and extranodal involvement was common. Patients were followed up for 1-144 months, 8 patients were treated with R-CHOP regime, CHOP regime or rituximab; 5 patients were stable, 4 patients died, and 1 case lost to follow up. Patients with pSS are closely associated with an enhanced risk of lymphoma, especially NHL. The clinical manifestations were complicated and varied.

Characteristics of intestinal flora in patients with primary Sjögren syndrome / 南方医科大学学报

OBJECTIVE@#To investigate changes in intestinal flora in patients with primary Sj?gren syndrome (pSS) and explore the relationship between pSS disease activity and intestinal flora structure.@*METHODS@#Fecal samples were collected from 18 female pSS patients, including 9 patients with active disease (group A) and 9 with disease inactivity or low activity (group B), with 10 healthy subjects as the control group. The total bacterial DNA was extracted from the fecal samples for PCR amplification, and Illumina Hiseq 2500 high-throughput sequencing was performed for the v3-v4 region of 16Sr DNA gene to obtain the biological information of the intestinal flora. The intergroup OTU analysis, structural diversity analysis, significant difference analysis and LEFSE analysis were performed with information mining of the literature think tanks.@*RESULTS@#The dilution curves generated based on the OTUshannon index for analysis of sample complexity showed that the measured data were relatively complete and could reflect the diversity of the microorganisms in the subjects. Analysis of the Alpha diversity index showed that the Shannon index differed significantly between group A and group B, and the Simpson index differed significantly between group A and group B and between group A and the control group ( < 0.05). Sequence analysis the 3 groups all consisted mainly of 4 phylum (, , , showed that the intestinal flora in and ) and 4 genera (, , , and ), all showing no significant differences among the 3 groups ( > 0.05) with the exception of genus, which differed significantly among the 3 groups ( < 0.05). The 16S v3-v4 region in the genus , , , , , , , , , , -, and differed significantly among the 3 groups ( < 0.05). The high-dimensional biometrics and genomic characteristics of the intestinal microorganisms differed significantly among the 3 groups ( < 0.05). According to the size of LDA SCORE (effect size), the core flora in group A included the genera , , -, , -, , , , and , as compared with the genera , , , , , -, , - and in the control group.@*CONCLUSIONS@#Patients with pSS have significant changes in the diversity of intestinal flora, especially in some specific bacteria in genus and in 16S v3-v4 region of the bacteria. The differences in the core bacteria in the intestinal flora of pSS patients suggest the role of flora structure changes in the pathogenesis of pSS.

Advances in the clinical research on autoimmune liver disease with Sj gren’s syndrome / 临床肝胆病杂志

Autoimmune liver disease is a group of liver diseases caused by the disorder of the autoimmune system, and some patients may have the symptoms of dry mouth and dry eyes. Patients with autoimmune liver disease and Sj gren’s syndrome are commonly seen in clinical practice. This article summarizes the research advances in the clinical manifestation, pathological features, key diagnosis/treatment points, and prognosis of autoimmune liver disease with Sj gren’s syndrome.