Ziwan-Taoren herb pair can exert an therapeutical effect in primary Sjogren’s syndrome through inhibiting the TLR/NF-κB pathway

Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still unknown.This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS.Methods:Firstly,the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis.Secondly,the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques.Finally,efficacy and mechanism were conducted through in vivo experiments,such as water intake,spleen index,hematoxylin-eosin staining pathological changes,ELISA,Western Blot analysis,and immunofluorescence staining.Results:Nine active compounds were extracted from network pharmacology,including quercitrin,luteolin,kaempferol,β-sitosterol,isorhamnetin,galangin,hederagenin,diosmetin and gibberellin 7.Seven disease targets were identified:RELA,TP53,AKT1,interleukin(IL)6,MAPK1,ESR1,IL10;with RELA being the most core target.KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process.preliminary results of molecular docking showed that ZT’s active compounds bind well to the RELA(p65)receptor.In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice.The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased,while levels of inflammatory factors such as tumor necrosis factor-α,IL-6,and IL-1βalong with protein expressions including toll-like receptor4,p-p65 and p-IKKα/βin NF-κB pathway were reduced.Conclusions:The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS,potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway.

Visual resolution under photopic and mesopic conditions in patients with Sjogren's syndrome

AIM:To focus on different visual resolution tasks under photopic and mesopic conditions in Sjogren’s syndrome patients compared to age-matched healthy controls.METHODS:The visual resolution measurements included high and low visual acuities and contrast sensitivity functions.These tests were conducted under photopic and then mesopic conditions.Twenty-one Sjögren’s syndrome patients and 21 aged-matched healthy volunteers completed all the measurements in this study.RESULTS:Sjogren’s syndrome patients have greater impairment in contrast sensitivity than standardized visual acuity.This reduction was significant under the mesopic condition.Also,Sjogren’s syndrome patients treated with pilocarpine suffer more than patients without pilocarpine treatment under low light conditions.CONCLUSION:Sjogren’s syndrome patients shows greater impairment in different visual resolution tasks due to dry eye symptoms.

Persistent Xerophthalmia in a Patient with Rheumatological Disease and Priiviary Sjogren’s Syndrome: Case Report from Northern Brazil

This case study aims to contribute to the literature in order to highlight the importance of this collaboration between medical specialties. A female patient R.N.N. F, age 66, from the city of Manaus, with a previous diagnosis of Sjogren’s syndrome in regular follow-up by the Rheumatology team at the Araujo Lima outpatient clinic and referred to the Ophthalmology sector for complementary evaluation related to visual discomfort. The fundoscopy performed in the patient was within normal limits, but the symptoms experienced by her proved to be an important clinical finding, which has ratified the need for regular and multidisciplinary follow-up. This report unequivocally demonstrates that even in the face of tests considered within the expected limits for a given population, the clinical presentation can be specific and particular for each analyzed individual. Early screening exams should contemplate the patient in a holistic and individualized way whenever possible.

鱼鳞样红皮症-痉挛性截瘫-智力发育不全综合征(Sjogren-Larsson综合征)(附1例报道及文献分析)

报道1例中国人的Sjogren-Larsson综合征,并结合文献复习,探讨Sjogren-Larsson综合征的临床表现、影像学特征、基因检测和治疗。

Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjogren's syndrome

Neuromyelitis optica spectrum disorder often co-exists with primary Sjogreffs syndrome. We compared the clinical features of 16 neuro- myelitis optica spectrum disorder patients with （n = 6） or without primary Sjogreffs syndrome （n = 10）. All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjogren＇s syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinudear autoantibody, anti-Sjogren＇s-syndrome-related antigen A an- tibodies, anti-Sjogren＇s-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjogren＇s syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% （4/6） of patients with primary Sjogren＇s syndrome and in 60% （6/10） of patients without primary Sj6gren＇s syndrome. More brain abnormalities were observed in patients without primary Sj6gren＇s syndrome than in those with primary Sj6gren＇s syndrome. Segments lesions （〉 3 centrum） were noted in 50% （5/10） of patients without primary Sj6gren＇s syndrome and in 67% （4/6） of patients with primary Sjogren＇s syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjogren＇s syndrome are similar. However, neu- romyelitis optica spectrum disorder patients without primary Sjogreffs syndrome have a high frequency of brain abnormalities.

Comparison of corneal biomechanics in Sjogren's syndrome and non-Sjogren's syndrome dry eyes by Scheimpflug based device

AIM：To compare the corneal biomechanics of Sj？gren＇s syndrome（SS） and non-SS dry eyes with Corneal Visualization Scheimpflug Technology（CorV is ST）.METHODS：Corneal biomechanics and tear film parameters, namely the Schirmer I test value, tear film break-up time（TBUT） and corneal staining score（CSS） were detected in 34 eyes of 34 dry eye patients with SS（SSDE group） and 34 dry eye subjects without SS（NSSDE group） using CorV is ST. The differences of the above parameters between the two groups were examined, and the relationship between corneal biomechanics and tear film parameters were observed. RESULTS：The differences in age, sex, intraocular pressure（IOP） and central corneal thickness（CCT） were not significant between the two groups（P〉0.05）. The tear film parameters had significant differences between the SSDE group and NSSDE group（all P〈0.05）. Patients in the SSDE group had significantly lower A1-time and HC-time, but higher DA（P=0.01, 0.02, and 0.02, respectively） compared with the NSSDE group. In the SSDE group, DA was negatively correlated with TBUT（rho=-0.38, P=0.03）; HC-time was negatively correlated with CSS（rho=-0.43, P=0.02）. In the NSSDE group, HC-time was again negatively correlated with CSS（rho=-0.39, P=0.02）.CONCLUSION：There are differences in corneal biomechanical properties between SSDE and NSSDE. The cornea of SSDE tends to show less ＂stiffness＂, as seen by a significantly shorter A1-time and HC-time, but larger DA, compared with the cornea of NSSDE. Biomechanical parameters can be influenced by different tear film parameters in both groups.

正常人与Sjogren综合征患者唇腺免疫细胞的研究

干燥综合征又称Sjogren综合征(SS),目前认为是一种自身免疫性疾病,其发病机制仍不十分清楚.本实验采用免疫组化链菌素-过氧化物酶复合物(LSAB)技术,对SS患者组织学及淋巴细胞亚群HLA-DR+细胞系统分析,探讨SS与各免疫细胞间的关系.

Sjogren氏综合征患者唇腺活检标本的病理学观察

观察了９６例Ｓｊｏｇｒｅｎ氏综合征患者唇腺活检标本的病理学改变。根据炎细胞的浸润程度和类型、腺泡的破坏、导管及间质的改变等，将病变分为急性活动期、慢性静止期、慢性进展期，并提出了病理诊断标准。认为该分期方法对判断病变的进展程度和状态有一定作用。

Total glucosides of paeony alleviates Sjogren syndrome through inhibiting inflammatory responses in mice

OBJECTIVE To study the therapeutic effects of TGP on SS both in C57BL/6J mice immunized by immu⁃nological induction(SS mice)and NOD/ShiltJNju(NOD)mice.METHODS TGP(180,360,720 mg·kg^-1)was intragastri⁃cally administered for 6 or 16 weeks for SS mice and NOD mice,respectively.Weekly food and water intake,saliva flow,submandibular gland(SMG)and spleen index,and SMG pathology were measured.ELISA was used to evaluate serum interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and autoantigens(SSA/Ro,SSB/La,andα-fodrin).Real-time PCR and Luminex liquid suspension chip assay were applied to analyze SMG inflammatory cytokines mRNA TNF-α,IL-17A,CXCL9,CXCL13,and B-cell activating factor(BAFF)and protein(IL-1β,IL-6,TNF-α,and IFN-γ)expres⁃sion.RESULTS Compared with SS mice,TGP(720 mg·kg^-1)treatment increased saliva flow,reduced organ indexes,and decreased serum IL-6 and IFN-γ concentration.TGP(360 mg·kg^-1)treatment decreased serum IFN-γ concentra⁃tion.TGP(180,360,720 mg·kg^-1)treatment improved SMG pathological damage.Compared with NOD mice,the saliva flowincreased from 9 to 15 weeks of administration.After 2 weeks of administration,TGP(720 mg·kg^-1)treatment decreased serum SSA/Ro,SSB/La and a-fodrin concentration,increased SMG index,inhibited SMG IFN-γ concentra⁃tion,and down-regulated SMG TNF-α,IL-17A,CXCL9,CXCL13 and BAFF mRNA expression.TGP(360 mg·kg^-1)treat⁃ment decreased serum SSB/La and a-fodrin,and SMG TNF-α and IFN-γ concentration,and down-regulated SMG TNF-α,IL-17A,CXCL9 and BAFF mRNA expression.TGP(180 mg·kg^-1)treatment decreased serum SSB/La,a-fodrin,and SMG IL-1β concentration,and down-regulated SMG TNF-α,IL-17A and BAFF mRNA expression.After 8 weeks of administration,TGP(180,360,720 mg·kg^-1)treatment increased SMG index,and decreased serum a-fodrin concentra⁃tion.TGP(720 mg·kg^-1)treatment down-regulated mRNA expression of SMG TNF-α,IL-17A,CXCL9,CXCL13,and BAFF.TGP(360 mg·kg^-1)treatment reduced mRNA expression of TNF-α,CXCL9,CXCL13 and BAFF,and concentra⁃tion of IL-6 and TNF-α.TGP(180 mg·kg^-1)treatment down-regulated mRNA expression of TNF-α,CXCL9,and CXCL13,and decreased IL-6 and TNF-αconcentration in SMG.After 16 weeks of administration,TGP(180,360,720 mg·kg^-1)treatment reduced serum SSA/Ro and a-fodrin concentration,increased SMG index,and decreased SMG CXCL13 and BAFF mRNA expression.TGP(360,720 mg·kg^-1)treatment decreased serum SSB/Laconcentration and SMG TNF-α,IL-17A and CXCL9 mRNA expression.Besides,TGP(180,360,720 mg·kg^-1)treatment alleviated the pathological damage of SMG after 2 and 16 weeks of administration.CONCLUSION TGP has a certain therapeutic effect onmice through inhibiting inflammatory responses.

EXPERIENCE ON 60 CASES OF SJOGREN'S SYNDROME DIAGNOSED AND TREATED WITH TRADITIONAL CHINESE MEDICINE

Sjgren syndrome is a systematic inflama-tory,auto-immune chronic disease.Since 1981,60 cases have been treated by means of TCMwith certain effect as following.

Gastrointestinal microbiome and primary Sjogren’s syndrome: a review of the literature and conclusions

The recognition of the profound impact of the human gastrointestinal microbiome(GM) on human autoimmune diseases has gradually increased thanks to deeper research efforts. As a systemic autoimmune disease, primary Sjogren’s syndrome(pSS) cannot be completely cured. Human studies have revealed that GM species and diversity are altered in patients with p SS compared with healthy individuals. Animal studies have provided possible mechanisms for the association between pSS and GM. The potential role of GM in pSS is exerted through several mechanisms. GM dysbiosis leads to increased intestinal permeability, which increases the risk of GM antigen exposure and activates specific autoreactive T lymphocytes via “molecular mimicry”. In addition, GM antigen exposure and intestinal immune tolerance loss caused by GM dysbiosis together induce chronic local gut mucosal inflammation, which deteriorates to systemic chronic non-specific inflammation with the circulation of pro-inflammatory lymphocytes and cytokines. These factors eventually activate autoreactive B lymphocytes and lead to pSS. If GM plays a key role in the pathogenesis of pSS, clarifying the underlying mechanisms will be helpful for the development of new therapies targeting GM for dry eye associated with pSS. This review summarizes the latest knowledge about the relationship between GM and p SS,with the aim of contributing to future research and to the development of new clinical applications.

Pulmonary amyloidosis and multiple myeloma mimicking lymphoma in a patient with Sjogren’s syndrome:A case report

BACKGROUND Sjogren’s syndrome(SS),which affect salivary gland function,is an autoimmune disease.SS may involve extraglandular organs.Approximately 10 to 20 percent of SS patients have clinically significant lung disease,but presentation of pulmonary amylodosis is extremly rare.The incidence of benign monoclonal gammopathy in SS patients is high,but multiple myeloma is rare.No case involving the simultaneous occurrence of two rare diseases,pulmonary amyloidosis and multiple myeloma,in the same patient with SS has been reported so far.CASE SUMMARY A 41-year-old male patient was referred to our hematology department due to incidentally detected gastric plasmacytoma.He had been diagnosed with SS four years earlier.Multiple miliary nodules,ground glass opacity in both lung fields,and enlargement of both inguinal lymph nodes was observed on chest and abdomen computer tomography.Based on the pathological findings of lung and lymph node biopsied specimens,the patient was diagnosed with pulmonary amyloidosis and multiple myeloma.Pulmonary amyloidosis and multiple myeloma associated with SS has rarely been reported.CONCLUSION This is an extremely rare case of simultaneous pulmonary amyloidosis and multiple myeloma in the same patient with SS.

NF-κB Controls Resistance of Human Salivary Gland (HSG) Cells to Apoptosis in an <i>in Vitro</i>Model of Sjogren’s Syndrome

Aim: To elucidate the anti-apoptotic properties of nuclear factor kappa light-chain-enhancer of activated B cells (NF-κB) and feedback regulation of NF-κB by nuclear factor of kappa light-chain-enhancer of activated B-cells inhibitor alpha (IκBα). Methods: We developed an in vitro model of Sjogren’s syndrome by transfecting human salivary gland (HSG) and acinar cells (NS-SV-AC) with a plasmid-encoding IκBαM (pCMV-IκBαM), a degradation-resistant IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha)-mutant, and examined TNF-induced apoptosis and anti-apoptotic properties of NF-κB. Apoptosis and induction of pro-apoptotic and anti-apoptotic genes were investigated by cDNA arrays, RT-PCR, electrophoretic mobility shift assays, and western blot. Results: In the presence of NF-κB inhibitors, TNF-induced apoptosis was markedly increased in both salivary gland and acinar cells. Increased caspase-3 activity was present in both HSG and NS-SV-AC cells. IκBαM-transfected salivary gland cells were more sensitive to TNF-induced apoptosis than IκBαM-transfected acinar cells. Transcription of pro-apoptotic genes was confirmed in both HSG and NS-SV-AC cells that were transfected with IκBαM. Results from caspase-3 activity assay confirmed previous experiments showing an apoptotic role for NF-κB. Conclusion: Data from gene expression arrays suggest that different mechanisms may operate during TNF-induced apoptosis in salivary gland ductal and acinar cells.

Hypergammaglobulinemic purpura of waldenstorm associated with sjogren’s syndrome in a young female responding to rituximab treatment

Hypergammaglobulinemic Purpura of Waldenstorm is one of the uncommon conditions with purpura and is often associated with collagen vascular disease. It is difficult to treat and sometimes needs anti CD 20 molecules for resistant cases.

Primary Sjogren’s syndrome and focal proliferative and crescentric necrotizing glomerulonephritis

Intro: Primary Sjogren’s syndrome is a chronic systemic autoimmune disease. Although ocular and oral dryness are the hallmarks of this syndrome, renal involvement when present most commonly has the histological appearance of tubointerstitial nephritis and less often glomerular involvement. We report, a unique case of renal manifestations of primary Sjogren’s syndrome with a proven histological focal proliferative and crescentric necrotizing glomeru-lonephritis. Case: A 30 years old man with Kimura disease presented with four months of subjective fevers, migrating skin erythema, dry mouth, and dry eyes. On further workup the patient was found to have a positive ANA, positive anti-SSA, and was evaluated by ophthalmology who found keratoconjunctivitis sicca. The patient was started on hydroxychloroquine in combination with prednisone. On follow up, the patient was found to be hypertensive with acute kidney injury, a creatinine of 3.65, proteinuria and hematuria. Renal ultrasound was unremarkable. Cytoplasmic ANCA was positive and kidney biopsy was performed revealing non pauci-immune focal proliferative and necrotizing glomerulonephritis with cellular crescents and mesangial dense deposits by electron microscopy. Conclusion: To our knowledge, the association between biopsy proven focal proliferative and necrotizing glomerulonephritis with primary Sjogren’s syndrome has never been previously described in the literature, nor has there been a reported case of association between Kimura disease, ANCA serology and primary Sjogren’s syndrome.

Disseminated histoplasmosis in primary Sjogren syndrome:A case report

BACKGROUND Sj?gren syndrome(SS)is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands.And histoplasmosis is an invasive mycosis caused by the saprophytic dimorphic fungus H.capsulatum.In patients with primary SS(PSS),disseminated histoplasmosis(DH)is extremely rare.CASE SUMMARY We report a 37-year-old female patient admitted to our hospital with exacerbating fatigue,somnolence,and pancytopenia as the main symptoms.She was eventually diagnosed with DH based on pancytopenia,splenomegaly,and findings of bone marrow smears.The atypical clinical symptoms made the diagnosis process more tortuous.Unfortunately,she died of respiratory failure on the day the diagnosis was confirmed.CONCLUSION We present a rare and interesting case of DH in a PSS patient.This case updates the geographic distribution of histoplasmosis in China,and expands the clinical manifestations of DH in PSS,highlighting the significance of constantly improving the understanding of PSS with DH.

Effect Observation of Fluor Protector on Secondary Caries of Sjogren Syndrome Patients

Purpose:to observe the occurrence rate of secondary caries on sjogren syndrome patients by filling carious cavities with simply using resin materials and fluor protector added resin materials.Method:20 cases of sjogren syndrome patients,who were filled the decayed teeth in the Stomatology Department of our hospital from September 2015 to September 2016,and 155 carious cavities were selected to be involved in the experiment,and secondary caries would be determined in 3 months,6 months and 12 months after filling of carious cavities.Result:the occurrence rates of secondary caries in the experimental group after treatment in 3 months,6 months,12 months were 1.37%,2.74%,5.48%respectively;while the rates in the control group were 4.87%,7.32%,13.41%respectively.There was statistical significance between differences of the occurrence rates of secondary caries in two groups.Conclusion:the occurrence of intraoral secondary caries of sjogren syndrome patients can be effectively reduced by using fluor protector after filling decayed teeth.