Comparison of the meibomian gland dysfunction in patients with chronic ocular graft-versus-host disease and Sjogren's syndrome

AIM: To investigate the abnormalities in the meibomian gland in patients with dry eye disease(DED) associated with chronic ocular graft-versus-host disease(coGVHD) in comparison with Sj?gren's syndrome(SS), a major form of aqueous deficient DED and meibomian gland dysfunction(MGD), a common cause of evaporative DED.METHODS: A total 135 eyes of 135 subjects included in this study: patients with DED associated with coGVHD(n=30), patients with SS(n=35), patients with MGD(n=35), and normal controls(n=35). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire, ocular surface examination [Schirmer test, tear film breakup time(TFBUT), and ocular surface staining], and meibomian gland assessment [meiboscore(gland dropout detected on meibography using infrared camera of the Keratograph 5 M), meibum expressibility score(MES), meibum quality score(MQS), lid margin abnormality]. In addition, correlations of meibomian gland characteristics with ocular surface parameters as well as disease severity score were investigated in coGVHD group.RESULTS: The coGVHD group showed significantly higher meiboscore, MES, and MQS than the other 3 groups(all P<0.05). In the coGVHD group, parameters of meibomian gland showed a significant correlation each other and those of ocular surface. The correlation between meibomian gland parameters and severity score of co GVHD was also established(meiboscore, r=0.62; MES, r=0.47; MQS, r=0.47; lid margin abnormality score, r=0.55; all P<0.05).CONCLUSION: Patients with DED associated with co GVHD show poorer gland morphology and worse glandfunction than other types of DED. In addition, meibomian gland damage is not only associated with ocular surface damage but also disease severity of coGVHD.

Serum-negative Sjogren's syndrome with minimal lesion nephropathy as the initial presentation:A case report

BACKGROUND Primary Sjogren's syndrome(pSS)is an autoimmune disease,and renal involvement has been considered to be one of the systemic complications of pSS.Patients who have sjogren's syndrome with renal disease as the first manifestation and no exocrine gland involvement or autoantibodies can be missed clinically.CASE SUMMARY We here in report an unusual case of a primary Sjogren's syndrome in a 43-yearold female who had minimal lesion nephropathy as the initial presentation,and the patient was negative for serum anti-SSA and anti-SSB antibodies and did not have signs of exocrine gland involvement.The patient’s Sjogren's syndrome was confirmed by a minor salivary gland biopsy(MSGB)and a filter paper test.the patient’s oedema subsided,and the patient’s urinary protein resolved,showing that the treatment was effective.CONCLUSION MSGB should be considered if pSS is suspected in patients who do not have the typical pSS symptoms or who are positive for the specific autoantibodies.

Subclavian steal syndrome associated with Sjogren's syndrome: A case report

BACKGROUND Subclavian steal syndrome(SSS)caused by Sjogren's syndrome is rare,especially for elderly patients with risk factors for atherosclerosis.The current report presents the uncommon etiology and treatment of SSS,aiming to improve doctor’s clinical experience.CASE SUMMARY A 69-year-old man was diagnosed with hypertension and acute cerebral infarction presenting with left upper limb weakness and pain even gradually aggravating to left limb hemiplegia 30 years ago.He was managed with antihypertensive and antithrombotic therapy;however,his condition was recurrent,and he never had any further examination.It was found that the difference of the bilateral upper arm systolic pressure was over 20 mmHg,and Doppler examination showed that the blood flow of the left vertebral artery was reversed,suggesting SSS.Further tests revealed a benign lymphoepithelial lesion in salivary gland tissue,confirming the Sjogren's syndrome.CONCLUSION The patient was found to have hypertension when he was 33 years old,and the blood pressure of both sides was asymmetric,which was ignored.The patient's symptoms of dizziness and upper limb weakness were misdiagnosed as general cerebral infarction.It is necessary to test the aorta computed tomography angiography to prove secondary hypertension factors such as Sjogren's syndrome.

Meta analysis of efficacy and safety of traditional Chinese medicine combined with hydroxychloroquine sulfate in the treatment of Sjogren's syndrome

Objective:To systematically evaluate the efficacy and safety of traditional Chinese medicine combined with hydroxychloroquine sulfate in the treatment of Sjogren's Syndrome(SS).Methods:Two researchers searched the databases of Chinese National Knowledge Infrastructure(CNKI),Wanfang Database,Weipu Database,Chinese Biomedical Literature Database,PubMed Database,Web of science Database and The Cochrane Library Database(the retrieval period is from the establishment of the database to October 2020)and screened the literatures independently.The data were extracted for bias risk assessment,and then meta-analysis was performed using Revman 5.3 software.Results:A total of 19 articles involving 1185 patients were included,including 617 cases in the treatment group and 568 cases in the control group.Combined data analysis showed that the total effective rate of traditional Chinese medicine combined with hydroxychloroquine sulfate in the treatment of Sjogren's syndrome was significantly higher than that of hydroxychloroquine sulfate alone[R R=1.34,95%CI(1.24,1.44),P<0.00001].The improvement of salivary gland[SMD=0.66,95%CI(0.47,0.85),P<0.00001],tear secretion function[MD=2.56,95%CI(1.29,3.83),P<0.0001]and reducing CRP[MD=-3.53,95%CI(-3.93,-3.14),P<0.00001],ESR[MD=-5.80,95%CI(-8.48,-3.13),P<0.00001]were better than those of the control group.However,there was no significant difference in the reduction of IgG and the incidence of adverse reactions between the two groups.Conclusion:Traditional Chinese medicine combined with hydroxychloroquine sulfate in the treatment of SS is superior to the control group in total effective rate,improvement of salivary gland and tear secretion function,and reduction of CRP and ESR,and we didn’t see the significantly increase on the adverse event.However,due to the small sample size and low quality of the included studies,the conclusion needs to be verified by larger sample and higher quality randomized controlled trials.

Study on the correlation between TCM syndrome differentiation and immune inflammation index of Sjogren's syndrome

Objective:To observe the relationship between the distribution of TCM Syndromes of primary Sjogren's syndrome(pSS)and the changes of erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),immunoglobulin IgA,IgG and IgM.Methods:157 diagnosed PSS patients were divided into dampness heat obstructing collaterals syndrome,dryness evil invading lung syndrome,Qi blood stasis syndrome,liver kidney yin deficiency syndrome and Qi Yin deficiency syndrome according to TCM syndrome differentiation standard.The age,course of disease,general health score in international universal quality of life scale,self rating Anxiety scale(SAS),self rating Depression Scale(SDS)and erythrocyte sedimentation rate were observed and detected(ESR,C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),immunoglobulin IgA,IgG and IgM and other immune inflammatory indexes were detected.The relationship between different TCM Syndromes of PSS and molecular level changes of immune inflammatory indexes was analyzed and compared,as well as the impact on quality of life and mental emotion.Results:The overall health score of patients with Qi Yin deficiency syndrome was significantly lower than that of patients with dampness heat obstructing collaterals and dampness evil invading lung syndrome(P<0.01),while the SAS and SDS scores of patients with Qi Yin deficiency syndrome were significantly higher than those of patients with dampness heat invading lung syndrome and dampness heat obstructing collaterals syndrome(P<0.05,P<0.01);ESR,CRP,RF,TNF-α,IL-6,IgA,IgG and IgM related laboratory indexes of patients with dampness heat obstructing collaterals syndrome were significantly higher than those of patients with dry evil invading lung syndrome,liver kidney yin deficiency syndrome and liver kidney yin deficiency syndrome Qi Yin deficiency syndrome and Qi blood stasis syndrome(P<0.05,P<0.01).Correlation test found that the above five syndrome types were positively correlated with hs-CRP,IL-6,TNF-ɑindicators(P<0.05).Conclusion:The overall health,SAS,SDS and related hs-CRP,IL-6,TNF-ɑand some others indexes of SS patients are associated with TCM syndromes.

Study on immunological characteristics of T lymphocyte in peripheral blood from patients with sjogren's syndrome

Objective: To study on in immunological characteristics of T lymphocyte in peripheral blood from patients with Sjogren's syndrome (SS), provide the theory basis for the further research of Traditional Chinese medicine (TCM) targeted therapy.Methods:T lymphocyte subsets in peripheral blood from SS, RA and normal control groups were tested with various monocbnal antibodies and multicolor flow cytometry.T lymphocyte subsets were tested in peripheral blood from SS patients of different TCM Syndromes. The relationship between T Lymphocyte subsets and disease activity was measured by erythrocyte sedimentation rate (SR)and serum IgG. Results: The percentage of CD4^+T cells and the ration of CD4^+/CD8^+T cells in peripheral bbod from SS patients decreased significantly, and the percentage of CD8^+T cells increased than that in control groups (P<0.05). Compared with patients in inactive period, the percentage of CD4^+T cells in peripheral bLood from SS patients in the active stage increased (P>0.05), the percentage of CD8^+T cells decreased (P>0.05), and the ration of CD4^+/ CD8^+T cells increased (P<0.05).Compared with control groups, the percentage of CD69 expressed on T cells in peripheral blood from SS patients decreased, and the percentage of CD95's expression increased (P<0.05).The percentage of CD69CD95's expression also increased (P>0.05). There were no differences among CD4^+T cells, CD8^+T ceLs and CD4^+/ CD8^+ in peripheral blood from SS patients of different TCM Syndromes (P>0.05). CD69 and CD95's expression on SS patients of different TCM Syndromes was no significantLy different (P>0.05).T cell receptor Vβ(TCR Vβ) subfamilies gene in peripheral blood from SS patients and control groups were expressed in all. Compared witji control groups, Vβ 5.3,Vβ 13.1,Vβ 12,Vβ 7.2 had significant differences (P<0.05).Comparison of different TCM Syndromes in SS group: Vβ 13.1 and Vβ 14 were significantly different (P<0.05).Conclusion:There was dysimmunity on T lymphocyte subsets in peripheral blood of SS patients, which was related to disease activity;apoptosis after activation of autoreactive T cell may be induced by Chinese medicine;TCR Vβ subfamilies of different TCM syndromes were different, which noted that different autoreactive T cells of abnormal activation tended to result in different expression of TCM Different syndromes.

Treatment of Sjogren's Syndrome with Liver Depression

Liu Chunying is a famous old Chinese medicine doctor for more than 30 years.He has rich experience in the understanding and treatment of Sjogren's syndrome(SS).Liu Shi systematically discusses the etiology and pathogenesis of SS from the angle of liver depression.In the treatment,it is emphasized that"Muyu Da Zhi"is the first,with the addition and subtraction of the disease,to provide a new idea for the treatment of Sjogren's syndrome from liver depression,and to attach a test case.

Research progress on BDNF in Sjogren's syndrome with depressive disorder

Brain-derived neurotrophic factor(BDNF)is a widely studied neurotrophic factor,which plays an important role in the growth,development,dif-ferentiation,injury,repair,survival and apoptosis of nerve cells.More and more studies have found that there is a high prevalence of depressive disorders in patients with autoimmune diseases.Sjogren's syndrome is a chronic autoimmune exocrine disease characterized by lympho-cytic infiltration and exocrine gland destruction.Depres-sive disorders are common in patients with Sjogren's syndrome.The quality of life of patients with Sjogren's syndrome with depression was generally lower than that of patients with Sjogren's syndrome without depres-sion.In this article,we reviewed the research progress of BDNF and depression in Sjogren's syndrome at home and abroad.

A Case of Podocytic Infolding Glomerulopathy with Primary Sjogren's Syndrome and Hashimoto's Thyroiditis

To the Editor:Podocytic infolding glomerulopathy (PIG)was proposed as a new disease entity in 2008,[1] and great attention has been paid to PIG because of the rare pathological changes to glomeruli associated with it.PIG is characterized by specific changes to the thickened glomerular basement membrane (GBM), including microspheres,microtubular structures,and podocytic infolding.However,the clinical features and pathogenesis of PIG still remain unclear.To elucidate the characteristics of this glomerulopathy,accumulating more information from reported cases is necessary.Herein,we present a case of glomerulopathy showing podocytic infolding in association with primary Sjogren's syndrome (pSS)and Hashimoto's thyroiditis.

Ginsenoside Rbl Upregulating AQP5 Protein Expression and Alleviating Salivary Secretion Impairment in Ovariectomized SjOgren's Syndrome Mice

Sjogren's syndrome(SS) is an autoimmune disease characterized as the impairment of salivary secretion mediated by abnormal aquaporin 5(AQP5). Here we used AQP5 promoter as the target to screen the eflective components from natural drugs. Panax quinquefolius and its specific ingredient, Rbl, were identified to increase the AQP5 transcriptional activity and AQP5 expression. Then we investigated the possibility of Rbl binding to sex hormone receptors and demonstrated that Rbl bound specifically to estrogen receptor alpha(ERa), but not to androgen receptor. Next, we found that ERa overexpression magnified the effect of Rbl induced AQP5 transcription, and the silence of ERa blocked this effect, demonstrating that Rbl activated AQP5 transcription via ERa pathway. Importantly, we constructed SS mouse model and investigated the effects of Rbl on salivary secretion in vivo. SS mice exhibited significant impairment in salivary secretion and decreased AQP5 expression in the submandibular gland. Intriguingly, SS mice administered with Rbl exhibited dramatically increased salivary secretion, followed by decreased diary water consumption. In particular, Rbl up-regulated AQP5 expression localized in the submandibular gland, almost similar to the SS mice administered with estrogen. Our data demonstrated that Rbl bound with ERa to up-regulate AQP5 to increase saliva secretion, thus functioned as a potential natural phytoestrogen for the therapy of salivary secretion impairment in SS patients.

A case of Sjogren's syndrome evolving into multicentric reticulohistiocytosis

Introduction:Multicentric reticulohistiocytosis(MRH)is a rare disease that is known to affect the skin and joints,primarily.It is considered a rare form of non-Langerhans cell histiocytosis(Group C)that can cause destructive inflammatory arthritis involving both the small and large joints.Cutaneous eruptions of periungual,“coral beads”and nodules appearing over the distal fingers are considered pathognomonic clues for identifying this disorder.Histology evaluation of the cutaneous papules typically shows infiltrative histiocytes and multinucleated giant cells.Although no well-established therapies exist to date,a variety of immunosuppressants have been used with varying degrees of success.Case Description:A 53-year-old Caucasian female patient with a family history of rheumatoid arthritis and a personal history of Sjogren's syndrome presented to the rheumatology clinic complaining of pain in her bilateral hands and fingers.There were several small,papulo-nodular lesions ranging from 1 to 2mm in size noted at the base of her nails.A 4mm punch biopsy of one of the papules from the neck showed dermal infiltration of eosinophilic mononucleated and multinucleated giant cells with“ground glass”appearing cytoplasm consistent with MRH.X-ray of her hands showed periarticular demineralization and erosions surrounding several bilateral proximal and distal interphalangeal joints,and thus tofacitinib in addition to methotrexate,hydroxychloroquine,and dexamethasone(dosed weekly)was started to help control any further articular damage.Conclusion:Our aim is to further support the relation of MRH with autoimmune diseases,including Sjogren's syndrome.Autoimmune diseases have been reported in association with MRH,although a clear association has yet to be made.

Exploring salivary biomarkers and swallowing perceptions in Sjogren's syndrome:A case-control feasibility study

Background:The autoimmune disease Sjogren's syndrome(SS)is often characterized by salivary changes that may affect swallowing.No known study has investigated the association between salivary biomarkers and perceptions of swallowing in individuals with SS.Our objectives were to explore:(1)the operational feasibility of investigating saliva volume and composition,along with perceptions of swallowing,in those with and without SS;and(2)the relationship between saliva composition and perceptions of oral dryness,swallowing,and quality of life.Methods:We conducted a prospective,case–control feasibility study,collecting feasibility data(recruitment rate and optimal saliva collection methods)and whole mouth saliva samples(unstimulated and stimulated).We measured total protein content and conducted sialochemical(α-amylase,cortisol,C-reactive protein[CRP],and mucins),sialometric(flow rate),and perceptual(oral dryness and swallowing-related quality of life[SWAL-QOL])assessments.Our exploratory analyses focused on the main and fixed effects.We summarized all data descriptively,comparing:(a)outcomes between groups(t tests or Mann–Whitney U)and(b)salivary and perceptual data across participants(partial least-squares correlation[PLSC]).Results:We enrolled 12(N)participants(6 per group),all providing analyzable saliva.Cases had lower flow rate(p=0.003)and higher total protein,cortisol,and CRP concentrations(p<0.02)than controls.PLSC revealed inverse covariance between sialochemical and SWAL-QOL data across participants.Conclusion:Our study was feasible as designed.We explored novel relationships between salivary outcomes and participant-reported perceptions,distinguishing individuals with and without SS.Our findings support further study of saliva's role in perceptions of swallowing,specifically analytes with lubricative properties.

Effect of lymphotoxin blockage on different stages of Sjogren's syndrome in an animal model

Background:Lymphotoxin(LT)is an important mediator in Sjogren's syndrome(SS),both in patients and in animal models.Deletion of the LT alpha gene prevented the development of disease manifestations in the interelukin alpha transgenic mouse(IL14αTG)mouse model of SS.Aims:The current study was designed to evaluate the use of LT inhibitors at different stages of the disease in IL14αTG mice.Materials and Methods:IL14αTG mice were treated with anti‐LTa monoclonal antibody,LTb receptor‐immunoglobulin fusion protein(LTBR‐Ig)or isotype control during different stages of disease and analysis of salivary gland function,immunoglobulins,autoantibodies and histology of internal organs performed.Results and Discussion:The inhibitors were very effective in maintaining salivary gland function and preventing infiltration of the glands with lymphocytes when used in the early stages of the disease.Blocking LT at later stages of the disease did not recover salivary gland function but was still effective in limiting extra glandular manifestations including eye disease and tumor development.Some differences were noted in the effectiveness of anti‐LTαversus LTBR‐Ig in limiting particular disease manifestations.Conclusion:LT inhibitors deserve further investigation in the management of SS at whatever stage is identified.

Role of Helicobacter pylori infection in autoimmune systemic rheumatic diseases

The relationship between infection and autoimmunity has been increasingly defined over the last 20 years. The systemic rheumatic diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to self-antigen. The exact etiology for the majority of these diseases is unknown; however, a complex combination of host and environmental factors are believed to play a pivotal role. Helicobacter pylori(H. pylori) is one of the most widely studied infectious agents proposed as agents triggering autoimmune response. The persistent presence of H. pylori in the gastric mucosa results in chronic immune system activation with ongoing cytokine signaling, infiltration of gastric mucosa by neutrophils, macrophages, lymphocytes, as well as production of antibodies and effector T-cells. Various mechanisms have been proposed in an attempt to explain the extra-intestinal manifestations of H. pylori infections. These include: molecular mimicry, endothelial cell damage, superantigens and microchimerism. I performed a systematic literature review using the keywords "rheumatoid arthritis", "Sjgren's syndrome", "systemic sclerosis", "systemic lupus erythematosus","Helicobacter pylori " and "pathogenesis". A systematic literature search was carried out in MEDLINE; EMBASE; Cochrane Library and ACR/EULAR meeting abstracts. In systemic rheumatic diseases H. pylori infection prevalence alone should not be expected to provide sufficient evidence for or against a pathologic role in the disease. In this article Ⅰ review studies examining the potential involvement of H. pylori infection in autoimmune systemic rheumatic diseases. Further studies of the immunological response to H. pylori and its role in the pathogenesis of systemic rheumatic diseases are warranted.

Menstrual and Reproductive Characteristics of Patients with Primary Sjogren’s Syndrome:A 7-year Single-center Retrospective Study

Objective Primary Sjogren’s syndrome(pSS)is a systemic autoimmune disease that mainly affects the exocrine gland,especially in women.Currently,the results of studies on the menstruation or fertility of pSS patients remain controversial.This study aimed to examine the menstrual and reproductive characteristics of pSS patients.Methods Clinical data of 449 pSS patients who were admitted to Tongji Hospital in Hubei,China,from January 2015 to November 2021 were obtained and their menstrual and reproductive information analyzed.In addition,the clinical features of pSS patients with premenopausal or postmenopausal onset were compared.Results The spontaneous abortion rate of pSS patients was not higher than the reported rate of the general population and that the age of menarche,menstrual cycle,and menstrual period of pSS patients did not significantly differ from those reported in the general population;however,early menopause seemed to be more common in pSS patients.Skin involvement(27.96%vs.15.00%,P=0.005)and hyperglobulinemia(10.64%vs.4.16%,P=0.033)were more common in patients with premenopausal pSS onset,but patients with postmenopausal onset had a significantly greater incidence of interstitial lung disease(32.50%vs.17.02%,P=0.0004).Also,erythropenia(47.00%vs.31.25%,P=0.002),hypoalbuminemia(19.49%vs.8.22%,P=0.0009),and prevalence of high hypersensitive C-reactive protein levels(21.67%vs.10.94%,P=0.005)were more common in pSS patients with postmenopausal onset.Notably,the rate of abnormal pregnancy was significantly greater in patients with premenopausal onset(9.72%vs.2.50%,P=0.011).Conclusion Patients with pSS onset before or after menopause may have different risks in pulmonary involvement and laboratory manifestations.

Rehabilitation and pharmacotherapy of neuromyelitis optica spectrum disorder:A case report

BACKGROUND Neuromyelitis optica spectrum disorder(NMOSD)is a demyelinating autoimmune disease that affects the central nervous system.It typically manifests as optic neuritis or extensive longitudinal myelitis,with or without the presence of anti-aquaporin protein 4 autoantibodies(immunoglobulin G).CASE SUMMARY We report the case of a 45-year-old woman with a history of Sjogren's syndrome who was diagnosed with NMOSD accompanied by spinal cord injury and left calf intermuscular vein thrombosis.The patient received hormone shock and gamma globulin therapy in the acute phase and standard rehabilitation treatment during convalescence.Upon discharge,the patient was able to control urination and defecation,stand independently,and walk short distances with the aid of a walker.CONCLUSION This case suggests that pharmacotherapy and standard rehabilitation treatment can improve the prognosis of NMSOD patients.

Lessons from Sj?gren's syndrome etiopathogenesis:Novel cellular and molecular targets

Sjogren’s syndrome （SS） is a systemic autoimmune disease that affects primarily the lacrimal and salivary glands. In addition to a systemic autoimmune response directed against ubiquitous antigens （such as Ro and La antigens）, patients with SS mount a localized response that affects the epithelial component of exocrine glands leading to the establishment of a destructive inflammatory infiltrate comprised of activated T and B cells. Local chemokine and cytokine production drive the recruitment and local activation of immune cells that cause injury to acinar cells. CD4 T cells with different functional differentiation programs including Th1 （IFN-γ）, Th2 （IL-13, IL-4） and Th17 （IL-17, IL-21, IL-22） as well as diverse cytokine signaling pathways, are involved at the initiation, perpetuation, and progression of the disease. Which factors initiate this response and allow it to become chronic are unknown. Proposed mecha-nisms include viral infections and acinar cell apoptosis. Moreover risk-conferring genetic variants, probably through the facilitation of innate and adaptive immune activation, most certainly contribute to the creation of an underlying environment that fosters tolerance loss and facilitates perpetuation of the autoimmune response. In this review, we describe the mechanisms through which the immune response causes SS and emphasize the pathways that are amenable of being targeted with therapeutic purposes.

Protective Effect of Zengye Decoction(增液汤)on Submandibular Glands in Nonobese Diabetic Mice

Objective: To investigate the protective effect of Zengye Decoction(增液汤, ZYD) on the submandibular glands(SMGs) in nonobese diabetic(NOD) mice. Methods: Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine(HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon(IFN-γ), interleukin-10(IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide(VIP) in the submandibular glands were measured by realtime polymerase chain reaction. Results: Compared with the model group, the salivary flow of the ZYD group significantly increased(P<0.05), the extent of the histological changes was ameliorated(P<0.05), and the Th1/Th2 cytokine imbalance was remedied(P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated(P<0.05). Conclusions: ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.

Mechanism of cAMP-PKA Signaling Pathway Mediated by Shaoyao Gancao Decoction(芍药甘草汤)on Regulation of Aquaporin 5 and Muscarinic Receptor 3 Levels in Sjogren’s Syndrome

Objective:To investigate the mechanism of c AMP-PKA signaling pathway mediated by Chinese medicine formula Shaoyao Gancao Decoction(芍药甘草汤,SGD)on the regulation of aquaporin 5(AQP5)and muscarinic receptor 3(M3 R)levels in Sjogren’s syndrome(SS).Methods:Of the 30 mice,5 were randomly selected as control,and others were used for creating SS model.After successful modeling,mice were randomly divided into 5 groups(n=5 per group)and intragastrical y administered with saline(8 m L/kg),pilocarpine(1.4 mg/kg),or low,medium and high doses SGD(0.14,0.21,0.35 g/kg Radix paeoniae with 0.01 g/kg Radix glycyrrhizae,respectively)for 6 weeks.Human labial gland acinar cel s were treated with pilocarpine or varying doses of SGD with saline as the placebo.Hematoxylin and eosin staining was used to observe the histopathological changes of the submandibular glands of mice.The serum levels of anti-SS antigen A(SS-A),anti-SS antigen B(SS-B),M3 R,andα-fodrin in submandibular glands of mice were measured by enzyme-linked immunosorbent assay.Immunofluorescence staining was used to observe the spatial localization of AQP5 and M3 R in acinar cells.Reverse transcriptase polymerase chain reaction and Western blot were used to detect the expressions of PKA,c AMP,Epac1,AQP5,M3 R,nuclear factor kappa-B(NF-κB),and tumor necrosis factor(TNF)-αin submandibular gland tissues and cel s of each group.Results:Compared to normal mice,body weight,5-min salivary secretion,30-min secretion of tears and breakup time of tear film of model mice decreased at 1–6 weeks after immunization(al P<0.05),whereas water intake increased(al P<0.05).In the model group,glands of the submandibular glands showed atrophy,accompanied by acini of different sizes,decreased numbers and loose arrangement,with catheter dilatation and different degrees of lymphocyte infiltration.Conditions of mice in SGD groups were improved.The positive expression of AQP5 and M3 R were higher in the acinar cel s treated with al doses SGD compared to the normal group;serum levels of SS-A,SS-B,andα-fodrin were lower,and that of M3 R was higher in al doses SGD treated animals than the model or pilocarpine treated ones(al P<0.05).Compared to the model and pilocarpine groups,the m RNA and protein levels of NF-κB and TNF-αwere lower in mice or cel s treated with medium or high-dose SGD(al P<0.05),while those of PKA,Epac1,AQP5 and M3 R were higher(al P<0.05).Conclusion:SGD can improve symptoms of SS by regulating the c AMP-PKA signaling pathway and increasing AQP5 and M3 R levels.

Focus on Effects of Chinese Medicine on Improving Anxiety-Depression and Quality of Life of Patients with Primary Sjogren’s Syndrome

Primary Sjogren’s syndrome(pSS)is a chronic autoimmune disease with a long duration of illness,for which there is no cure.Patients often suffer from anxiety and depression due to various reasons,exhibiting a decline in their quality of life.Chinese medicine(CM)has certain advantages in the treatment of pSS,which not only helps relieve clinical symptoms and improve treatment outcomes,but also reduces anxiety and depression and improves the quality of life.Therefore,CM should be considered as early as possible given its effectiveness and synergistic effects in treating p SS.