Chuangqi Yu

miR-146a and miR-155 expression in PBMCs from patients with Sjögren's syndrome.

BACKGROUNDnAn increasing number of studies have revealed that microRNA (miRNA) contributes to the pathogenesis of autoimmune diseases. The objective of this study is to investigate the miR-146a and miR-155 levels in peripheral mononuclear blood cells from patients with primary Sjögrens syndrome (pSS) who were not receiving medications and to examine the correlations between these miRNA levels and the clinical features of the disease.nnnMETHODnUsing real-time polymerase chain reaction analysis of miRNAs, the miR-146a and miR-155 expression levels were assessed in peripheral mononuclear blood cells from 27 patients with pSS and 22 healthy controls, and the relationships between these miRNA levels and the visual analog scale (VAS) scores for dry mouth, dry eyes, and parotid gland swelling were investigated.nnnRESULTSnCompared with the healthy controls, the miR-146a expression level was significantly increased in the patients with pSS (Pxa0=xa00.0182) and was positively correlated with the VAS scores for parotid swelling (rxa0=xa00.4475, Pxa0=xa00.0192) and dry eyes (rxa0=xa00.4051, Pxa0=xa00.0361). Although the miR-155 expression level was significantly decreased in the patients with pSS (Pxa0=xa00.0131), the miR-155 expression positively correlated with the VAS score for dry eyes (rxa0=xa00.4894, Pxa0=xa00.0096).nnnCONCLUSIONnOur results demonstrated miR-146a overexpression and miR-155 underexpression in the peripheral mononuclear blood cells of the patients with pSS. Furthermore, the expression levels of these miRNAs correlated with the patients clinical features. Our data suggest that miR-146a and miR-155 might play important roles in the pathogenesis of pSS and that their expression levels may be useful for diagnosing pSS and for predicting disease activity and therapeutic responses.

Endoscopic observation and strategic management of obstructive submandibular sialadenitis.

PURPOSEnObstructive submandibular sialadenitis is a relatively common disease in the clinic. The present study explored the cause and strategic management of chronic obstructive sialadenitis using sialoendoscopy and surgery.nnnPATIENTS AND METHODSnFrom January 2005 to October 2007, 128 patients with obstructive symptoms in the submandibular gland were diagnosed using sialoendoscopy and occlusal films, and the obstructions were removed using interventional sialoendoscopy, surgery only, or combined techniques, depending on the size, shape, site, and quality of the sialolith in the duct. The shape and structure of the hilus of the submandibular gland was observed using sialoendoscopy.nnnRESULTSnIn the submandibular gland, the histologic features of 128 cases were identified endoscopically and radiographically. The endoscopic findings were of 3 types: sialolith in 114 (89%), mucus plug in 8 (6%), and stenosis in 6 (5%). Of 51 obstructions treated surgically, 47 were removed successfully, for a success rate of 92%. Of 63 obstructions treated using interventional sialoendoscopy, 52 were removed directly by sialoendoscopy, for a success rate of 83%. The unsuccessful cases were treated using sialoendoscopy or surgery. The obstructive symptoms were relieved in 12 of 14 patients without stones using dilation and irrigation under sialoendoscopy. Of the 114 patients with a stone, the sialoliths of 67 (59%) were located in the distal region (behind the first molar). The results showed that the more posterior the stone, the more difficult it was to remove. Three patients with treatment failure ultimately underwent resection of the gland. A basin-like structure in the hilus region was found in 86 (67%) of the 128 patients by sialoendoscopy. Finally, 5 patients were found to have a foreign body (fish bone) surrounded by a sialolith.nnnCONCLUSIONSnSialoendoscopy is a useful new technique, not to only detect the cause of obstruction in a submandibular gland, but also to treat the obstructive submandibular sialadenitis more effectively if incorporated with conventional surgical approaches.

Activation of TLR9-dependent p38MAPK pathway in the pathogenesis of primary Sjögren's syndrome in NOD/Ltj mouse.

OBJECTIVEnThe objective of this study was to investigate the potential role of Toll-like receptor 9-dependent p38 MAPK signaling pathway in the pathogenesis of primary Sjögrens syndrome (pSS) in NOD/Ltj mouse, aiming to identify an ideal target therapy model for human pSS.nnnMETHODSnNOD/Ltj mice were chosen as a model of pSS. The Toll-like receptor 9 and p-p38 MAPK double-positive peripheral blood mononuclear cells (PBMCs) of 4-, 5-, 8-, 10-, and 15-week-old NOD/Ltj mouse were analyzed by flow cytometry. The expressions of Toll-like receptor 9 and p-p38 MAPK in the submandibular gland (SMG) were also examined by immunohistochemistry. The change of stimulated salivary flow rate was dynamically measured, and the histopathology of SMG was evaluated by hematoxylin and eosin stain.nnnRESULTSnThe stimulated salivary flow rate in NOD/Ltj was reduced to 50-60% of the flow rate of control mice since the fifth week onwards. The Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs in both groups increased gradually from 5xa0weeks, peaked at 8xa0weeks and then gradually decreased at 10xa0weeks, yet the percentage of Toll-like receptor 9 and p-p38MAPK double-positive PBMCs in 5-, 8-, and 10-week-old NOD/Ltj mouse was significantly increased compared with those in control subjects. After the 10th week onwards, there were no significant differences in the Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs between NOD/Ltj mice and controls. Immunohistochemical staining showed that Toll-like receptor 9 was positive in the acinar epithelium cells and infiltrating lymphocytes in NOD/Ltj mice. p-p38 MAPK was detected in infiltrating lymphocytes and few ductal or acinar epithelium cells adjacent to infiltrating lymphocytes in NOD/Ltj mice.nnnCONCLUSIONSnFrom the fifth week till the tenth week, Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs were significantly increased in NOD/Ltj mice, accompanied with reduced stimulated salivary flow rate and Toll-like receptor 9 or p-p38 MAPK positive infiltrating lymphocytes observed in the SMG of NOD/Ltj mouse. Our results indicated that activation of Toll-like receptor 9-depended p38 MAPK signal pathway in PBMCs was an early event in pSS which made NOD/Ltj as an ideal therapy model to test the treatment effects of p38 MAPK or Toll-like receptor 9 inhibitors on pSS.

Long non-coding RNA expression profile in minor salivary gland of primary Sjögren’s syndrome

BackgroundTo examine the roles of long noncoding RNAs (lncRNAs) in the regulation of primary Sjögren’s syndrome (pSS) and reveal the expression profile of lncRNAs in labial salivary glands (LSGs) in pSS patients.MethodThe expression of 63,431 lncRNAs and 39,887 mRNAs were determined in the LSG of four pSS patients and four healthy controls using microarray experiments. Validation was performed in 30 pSS patients and 16 controls using real-time PCR. LncRNA-mRNA co-expression and gene-pathway networks were constructed using bioinformatics software.ResultA total of 1243 lncRNAs (upregulated: 890, downregulated: 353) and 1457 mRNAs (upregulated: 1141, downregulated: 316) were differentially expressed in the LSGs of pSS patients (fold change >2, P <0.05). Eight of these lncRNAs were validated using real-time PCR. ENST00000420219.1 (3.13-fold), ENST00000455309.1 (2.51-fold), n336161 (2.45-fold), NR_002712 (2.41-fold), ENST00000546086.1 (1.94-fold), Lnc-UTS2D-1:1 (1.79-fold), n340599 (1.69-fold), and TCONS_l2_00014794 (1.28-fold) were significantly upregulated in pSS. There were strong correlations between these lncRNAs and β2 microglobulin, disease course, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), IgA, IgM, visual analogue scale (VAS) of parotid swelling and VAS of dry eyes. Computational analyses revealed that 28 of the differentially expressed (DE) mRNAs were associated with eight DE lncRNAs involved in chemokine signaling pathways, the nuclear factor-kappa B (NF-κB) signaling pathway, and tumor necrosis factor (TNF) signaling pathway.ConclusionsOur study revealed the expression profile of lncRNAs in LSGs of pSS patients. Many novel lncRNA transcripts that play important roles in the pathogenesis of pSS were dysregulated in pSS. Therefore, this study will aid in the development of new diagnostic biomarkers and drug therapies.

Foreign body induced sialolithiasis treated by sialoendoscopic intervention.

Objective The study aims to identify the impact of sialolith formation by reviewing the foreign body induced sialolithiasis treated by sialoendoscopic intervention. Methods The study group included 13 patients whose sialolithiasis was induced by foreign body. After the routine radiographic examination, sialoendoscopic procedures were performed. Then, the treatment protocol was designed. Results The occupations of the 13 patients included 5 fishermen, 3 office workers, 2 workers, 1 teacher, 1 farmer, and 1 retired police officer. All patients had a unique diet habit—seafood. Eleven patients had a remembered incident of implanted fish bone and the following symptoms, with either obstructions or infections. Only 2 of the 13 had no memory of such an injury. All the stones were in the ducts of submandibular glands. In 10 procedures, there was 1 solitary stone, whereas 2 stones were encountered in 3 procedures. After being removed, 16 stones were crushed to expose the fish bone nidus of the stone. There was relief of symptoms after the procedures. Conclusions This study supported the possibility that some sialoliths resulted from a retrograde migration within the salivary ducts. In our study, the occupations (fisherman), the diet habit (seafood), and the injury history (a remembered incident of implanted fish bone and the following symptoms) were obviously related to the stone formation that was induced by the fish bone.

Endoscopic-assisted gland preserving therapy for the management of parotid gland sialolithiasis: Our preliminary experience

OBJECTIVEnTo analyze the efficacy and safety of sialendoscopy and a combined transoral or transcutaneous and sialendoscopic approach in the removal of parotid gland sialoliths.nnnMETHODSnThis retrospective study included 29 patients diagnosed with parotid gland sialolithiasis who required endoscopic-assisted gland preserving therapy. Ultrasonography and computed tomography were used to diagnose parotid sialolithiasis. The use of interventional sialendoscopy, sialendoscopic-transoral, or sialendoscopic-transcutaneous procedures was determined by the characteristics of the parotid gland stones.nnnRESULTSnThe stones were extracted by interventional sialendoscopy in nine patients. The transoral procedure was performed in 15 patients with large stones which were impacted in the ductal wall. The remaining five patients were managed through an external approach via a local incision under sialendoscopy. No postoperative complications occurred. The parotid glands were functioning normally after the procedures.nnnCONCLUSIONnThe combined sialendoscopic-transoral and sialendoscopic-transcutaneous operation appears to be a good alternative for parotid gland sialolithiasis in the absence of lithotripsy devices. This type of therapy can, therefore, decrease the rate of parotidectomy.

Clinical features and treatment outcomes of immunoglobulin g4-related sclerosing sialadenitis.

Abstract Idiopathic enlargement of salivary glands used to be confusing in diagnosis until immunoglobulin G4 (IgG4)–related sclerosing sialadenitis was proposed as a possible answer. In this case series, we reported the clinical features and management outcomes in 16 patients with IgG4-related sclerosing sialadenitis. We retrospectively studied 16 patients in clinical examination, serology, pathology, and sonography features. All patients were treated by corticosteroids and followed up for at least 3 months. The results of clinical features showed that all of the patients presented persistent, symmetric bilateral swelling of the salivary glands, elevated levels of serum IgG4, and/or IgG4-positive plasmacytes infiltration and tissue fibrosis. The results of all autoantibody tests were negative. The typical sonographic manifestation revealed multiple hypoechoic foci with an irregular netlike diffuse lesion in salivary glands. Most patients showed excellent response to steroids treatment. We conclude that, for patients who present (1) symmetric swelling of bilateral salivary glands for more than 3 months, (2) elevated serum IgG4 level (>135 mg/dL), and (3) enlargement in bilateral salivary glands with multiple hypoechoic areas (irregular netlike appearance) in the sonography, the diagnosis of IgG4-related sclerosing sialadenitis should be considered. A comprehensive understanding of the medical condition and appropriate pathology examination are the key to diagnose. Steroids treatment is effective, and a treatment plan should be set up and followed in the long-term.

Bilateral aplasia of the major salivary glands and unilateral atresia of lacrimal duct.

Aplasia of the major salivary glands, especially the parotid gland, is a rare disorder. Up to now, few cases have been reported. Clinically, patients may present with xerostomia, irritable eyes, severe dental caries, or asymptomatic manifestations.According to clinical and radiologic findings, we reported a case of a 20-year-old girl with bilateral aplasia of the major salivary glands and unilateral atresia of the lacrimal duct and made telephone follow-up 1 year later.

Aberrant expression of the innate restriction factor bone marrow stromal antigen-2 in primary Sjögren's syndrome

OBJECTIVEnThe objective of this study was to analyze bone marrow stromal antigen-2 (BST-2) levels in labial glands, total peripheral blood mononuclear cells (PBMCs) and PBMC subpopulations from primary Sjögrens syndrome (pSS) patients and determine the correlation between BST-2 expression and clinical characteristics.nnnMATERIALS AND METHODSnPBMC subsets were positively separated using magnetic microbeads. BST-2 mRNA levels in labial glands, total PBMCs and PBMC subsets of 30 pSS and 30 healthy control (HC) subjects were investigated using real-time polymerase chain reaction (RT-PCR). Distribution of BST-2-positive cells in the labial glands was assessed by immunohistochemistry.nnnRESULTSnBST-2 was significantly increased in pSS labial glands and was positively correlated with the VAS value for parotid gland swelling and rheumatoid factor and β2-microglobulin serum levels. BST-2 levels were statistically different between pSS patients with positive and negative expression of anti-SSA antibody. Positive focal infiltrating lymphocytes and adjacent ductal epithelial cells were observed in labial glands from pSS patients, while there were a few scattered positive ductal epithelial cells in controls. BST-2 was also up-regulated in CD19+xa0B cells and the remaining CD4-CD8-CD19- PBMCs.nnnCONCLUSIONnBST-2 was aberrantly expressed in pSS patients, and expression in labial glands was positively correlated with important clinical characteristics; thus, it may be a potential biomarker of pSS activity.

Function of the parotid gland in juvenile recurrent parotitis: a case series

Our aim was to find out how the parotid gland functions in 44 patients with juvenile recurrent parotitis, and to assess the value of measuring the serum amylase activity. Clinical and personal details were recorded, and all patients had their serum amylase activity measured together with sialography during the chronic phase. The function of the gland was classified by sialographic images. The chi square test and Spearmans rank correlation coefficient were used in the statistical analyses. There was a significant association between the degree of glandular function and serum amylase activity (p=0.014). The patients with unilateral and bilateral disease differed significantly in their degree of glandular function (p=0.020), those with bilateral disease having poorer function. There were no significant correlations between other clinical variables and glandular function. Serum amylase activity is an important diagnostic variable in juvenile recurrent parotitis, and poor parotid function reflects the severity of the disease.