Lactate-induced mtDNA Accumulation Activates cGAS-STING Signaling and the Inflammatory Response in Sjögren's Syndrome.

Acinar epithelial cell atrophy in secretory glands is a hallmark of primary Sjögren's syndrome (pSS), the cause of which is far from elucidated. We examined the role of acinar atrophy by focusing on the metabolism of glandular epithelial cells and mitochondria in the pSS environment. After confirming the presence of a high-lactate environment in the labial glands of human pSS patients, we used the A253 cell line and NOD/Ltj mice as models to investigate the metabolic changes in salivary gland epithelial cells in a high-lactate environment in vitro and in vivo. We found that epithelial cells produced high levels of IL-6, IL-8, IFN-α, IFN-ß and TNF-α and exhibited significant NF-κB and type I IFN-related pathway activation. The results confirmed that lactate damaged mitochondrial DNA (mtDNA) and led to its leakage, which subsequently activated the cGAS-STING pathway. Inflammatory cytokine production and pathway activation were inhibited in vivo and in vitro by the lactate scavenger sodium dichloroacetate (DCA). Our study provides new insights into the etiology and treatment of pSS from the perspective of cell metabolism.

Sialendoscopy-assisted combined approach for parotid sialolithotomy: Our long-term experience.

OBJECTIVES: To assess the long-term outcome of sialendoscopy-assisted combined approach for parotid sialolithotomy with gland preservation. PATIENTS AND METHODS: A retrospective study of patients treated with a combined sialendoscopic and open approach was conducted between 2011 and 2020. Demographic data of patients such as operative technique, stone size, stone location, complications, and symptom relief were collected. Patients were followed up via clinical examination and questionnaires. RESULTS: Seventy-four patients were included and underwent endoscopy-assisted combined operations for the removal of 98 parotid stones. Of the 98 stones, 92(94%) stones were completely removed and 6(6%) were partially removed. At a mean follow-up of 47.1 ± 35 months, 65 of 74 patients (88%) achieved long-term success. Patients with stone incomplete removal were significantly more often to develop the recurrence of obstructive symptoms (p = 0.000) There were no cases of facial nerve injury or fistula formation. Gland function was preserved in 73 of 74 patients (99%). CONCLUSIONS: The combined approach for parotid stones is a safe and gland-preserving alternative to parotidectomy. The techniques described here show high success rates and good long-term results, and they avoided the need for gland resection in >95% of cases.

Arthroscopic Disk Repositioning After Failed Open Disk Repositioning.

PURPOSE: Open disk repositioning has been long achieving excellent functional and stability outcomes. However, still remains some relapses for whom a second open surgery is often challenging. This study aimed to evaluate the effectiveness of arthroscopic disk reposition as an alternative surgery for unsuccessful cases of anterior disk displacement (ADD) after an initial open disk repositioning. MATERIALS AND METHODS: This retrospective study included all patients who underwent secondary arthroscopy for disk repositioning of the relapsed ADD after an initial open surgery between January 2012 to June 2017. The redo arthroscopic disk repositioning and suturing procedure was the primary predictor input variable in this study. Outcome evaluation was based on both clinical (visual analog scale and maximal interincisal opening) and magnetic resonance imaging data. RESULTS: Twenty-seven joints fulfilling the inclusion criteria were included. A significant improvement was detected at 24-month postoperatively compared with the baseline visual analog scale. The maximal interincisal opening showed a statistical improvement from 25.07 mm preoperatively to 38.44 mm at 24-month postoperatively. Twenty-six joints maintained a stable disk position with only 1 joint relapsed to ADD without reduction. CONCLUSION: Arthroscopic disk reposition and suturing technique is a reliable and effective repeat surgery after failed initial open disk repositioning for management of ADD.

Inhibition of CD4 + T cells by fanchinoline via miR506-3p/NFATc1 in Sjögren's syndrome.

The hyperproliferation and hyperactivation of CD4 + T cells in salivary gland tissues are hallmarks of Sjögren's syndrome (SS). Fangchinoline (Fan) is extracted from the root of Stephania tetrandra Moore, which is used for treating rheumatic diseases in many studies. This study aimed to identify the mechanism underlying the inhibition of CD4 + T cells by Fan in the SS model NOD/ShiLtj mice. In vivo, Fan alleviated the dry mouth and lymphocyte infiltration in the salivary gland tissues of the NOD/ShiLtj mice and inhibited the number of CD4 + T cells in the infiltrating focus. In vitro, Fan's inhibitory effect on the proliferation of mouse primary CD4 + T cells was verified by CFSE and EdU tests. Furthermore, qRT-PCR and WB analysis confirmed that Fan could inhibit the expression of NFATc1 (Nuclear factor of activated T-cells, cytoplasmic 1) by upregulating miR-506-3p. Dual luciferase reporter gene assay suggested that miR-506-3p interacted with NFATc1. CFSE and EdU tests showed that Fan could inhibit the proliferation of CD4 + T cells through miR-506-3p/NFATc1. The key role of NFATc1 in the activation of CD4 + T cells and the high expression of NFATc1 in samples from SS patients suggested that NFATc1 might become a therapeutic target for SS. In vivo, 11R-VIVIT (NFATc1 inhibitor) alleviated SS-like symptoms. This study not only explained the new mechanism of Fan inhibiting proliferation of CD4 + T cells and alleviating SS-like symptoms but also provided NFATc1 as a potential target for the subsequent research and treatment of SS.

Efficacy Evaluation of Temporomandibular Arthroscopic-Assisted Masseter Nerve Avulsion on Hemimasticatory Spasm.

PURPOSE: Hemimasticatory spasm (HMS) is a masticatory muscle disorder without an effective treatment approach at present. This retrospective analysis aims to investigate the clinical efficacy of temporomandibular arthroscope-assisted masseteric nerve avulsion on HMS and thereby further determine a more effective therapeutic strategy for HMS patients. METHODS: Four patients with HMS receiving temporomandibular arthroscope-assisted masseteric nerve avulsion in the neurology department of oral surgery of our hospital from April 2017 to April 2018 were recruited in this study. Through a clinical follow-up period of 36 months, the comprehensive efficacy of arthroscope-assisted masseteric nerve avulsion was evaluated combined with an electrophysiological electromyogram. Furthermore, the maximum muscle strength and masticatory efficiency of the sound and affected sides were measured to determine whether there were complications. The morphology of the myelin sheath of the masseteric nerve avulsed in the operation was observed under the transmission electron microscope. RESULTS: The 3 years of follow-up showed that complete remission of HMS was seen in 4 patients with the score reduced to grade 0, showing satisfactory clinical efficacy. Electrophysiological electromyogram demonstrated an absence of obvious high-frequency group discharge potential in the 4 patients within 3 years after the operation, and the overall efficacy combined with the clinical efficacy was considered satisfactory. The maximum masseter strength of the sound side had no significant change, but that of the affected side was slightly decreased. The masticatory efficiency of the affected side was slightly decreased immediately after the operation but returned to the preoperative level 1 year after the operation, suggesting that this operation did not affect the masticatory function of the patients. No obvious demyelination was found in the avulsed nervous tissues. CONCLUSIONS: Temporomandibular arthroscope-assisted masseteric nerve avulsion yielded satisfactory and stable overall efficacy on the treatment of HMS. The masticatory efficiency of the affected side was optimally preserved, while the maximum masseter muscle strength of the affected side was partially decreased.

Prediction of 3-month treatment outcome of IgG4-DS based on BP artificial neural network.

OBJECTIVE: The study aimed to establish an effective back-Propagation artificial neural network (BP-ANN) model for automatic prediction of 3-month treatment outcome of IgG4-DS. METHODS: A total of 26 IgG4-DS patients at Shanghai Ninth People's Hospital from January 2018 to December 2019 were involved in the study. They were all followed for >3 months. The primary outcome was reduction of serum IgG4 (sIgG4) after 3-month treatment. The association between risk factors and reduction of sIgG4 was analyzed by Spearman's rank correlation test. According to the R values, we built a BP-ANN model by MATLAB R2019b. RESULTS: The average reduction of sIgG4 was 5.55 ± 5.03. After Spearman's rank correlation test, ESR, sIgG4, and sIgG were independently associated with reduction of sIgG4 (p < .05) and were selected as input variables. Take into account these parameters, BP-ANN model was developed and the coefficient of determination (R2 ) model was 0.95512. CONCLUSION: The BP-ANN model based on ESR, sIgG4, and sIgG could predict the 3-month reduction of sIgG4 for IgG4-DS patients. It showed potential clinical application value.

LncRNA PVT1 links Myc to glycolytic metabolism upon CD4+ T cell activation and Sjögren's syndrome-like autoimmune response.

The hyperproliferation and hyperactivation of CD4+ T cells in salivary gland tissue is a hallmark of Sjögren's syndrome (SS). However, the role of long noncoding RNAs (lncRNAs) in the pathological process of SS and CD4+ T cell activation has not been fully elucidated. Here, we reported that lncRNA PVT1 was involved in the glycolytic metabolism reprogramming and proliferation upon CD4+ T cell activation. Expression of PVT1 was positively related with CD4+ T cell activation both in SS patients and Ex vivo antigen simulation. Depletion of PVT1 decreased the proliferation of murine CD4+ T cells and Jurkat T cells upon activation. We also showed that expression of the transcription factor Myc is regulated by PVT1 under antigen simulation. Depletion of PVT1 significantly decreased the expression of glycolytic genes, as well as several pivotal glycolytic proteins that were directly transcribed by Myc. Measurement of glucose content and lactate secretion indicated a defected lactate secretion and glucose uptake in PVT1-depleted T cells. Additionally, the real-time extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) measurement also affirmed that PVT1 maintains glycolytic levels, glycolytic capacity under stress and ECAR/OCR ratios during T cell activation. Polarizing assays indicate that PVT1 depletion defected the function of Th1 effector cells as well as down-regulated Myc expression and glycolytic levels. Furthermore, we observed increased glycolytic levels in CD4+ T cells from SS-like NOD/Ltj mice. Treatment with 2-deoxy-d-glucose (2-DG), an inhibitor of glycolysis, significantly decreased the extent of lymphocyte infiltration and CD4+ T cell numbers and attenuated the defect of salivary flow in the lesioned submandibular glands of NOD/Ltj mice. Thus, our study demonstrated that lncRNA PVT1, which was upregulated in the CD4+T cells of SS patients, could maintain the expression of Myc, thus controlling the proliferation and effector functions of CD4+ T cells through regulating the reprogramming of glycolysis. Inhibition of glycolysis could attenuate the proliferation of CD4+ T cells and the SS-like autoimmune response. Our study provides a novel mechanistic function of lncRNA PVT1 in the pathogenesis of SS.

Dysregulated interleukin 11 in primary Sjögren's syndrome contributes to apoptosis of glandular epithelial cells.

The purpose of this study was to explore the potential function of interleukin-11 (IL-11) in the pathogenesis of primary Sjögren's syndrome (pSS) patients. Real-time polymerase chain reaction was performed to examine IL-11 expression in the labial glands of 30 pSS patients and 30 healthy controls. Immunohistochemistry was conducted to assess the distribution of IL-ll-positive cells in labial glands. The human salivary gland (HSG) cell line was used to study the effects of IL-11 on gland epithelial cells in vitro. Cell viability and cell proliferation were examined by CCK-8 kit and EdU assay, respectively. The population of apoptotic cells was detected in flow cytometry followed by Annexin V/PI and Hoechst staining. We found that the expression levels of IL-11 were remarkably decreased in pSS labial glands and were positively correlated with C-reactive protein levels and negatively correlated with rheumatoid factor levels. Fewer numbers of glandular epithelial cells were observed to be positively stained with IL-11 antibody in labial glands from pSS patients than those in healthy control patients. After IL-11 treatment, the viability and proliferation of HSG cells were significantly higher than those in the control group. The total apoptotic and necrotic rates of HSG cells in the group after IL-11 treatment were significantly lower. In conclusion, the results indicated that IL-11 promoted viability and proliferation and inhibited apoptotic and necrotic rates of glandular epithelial cells. In pSS, downregulated IL-11 might contribute to the apoptosis of salivary gland epithelial cells. However, it might be a potential target to alleviate the pathological atrophy of glandular epithelial cells in pSS patients.

Toll-like receptor 9 signaling promotes autophagy and apoptosis via divergent functions of the p38/JNK pathway in human salivary gland cells.

Abnormal signaling transduction in salivary gland cells is associated with the pathogenesis of Sjögren's syndrome (SS). Previously, we identified aberrant expression of toll-like receptor 9 (TLR9) in gland cells of SS patients and mouse models. In this study, we investigated the role of TLR9 and its downstream p38/mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) signaling in mediating apoptosis and autophagy in human salivary gland (HSG) cells. We selected either CpG-Odn, a classical TLR9 activator, or lentivirus-packaged TLR9 full-length cDNA to activate TLR9 signaling transduction. Activation of TLR9 signaling induced phosphorylation of its downstream protein kinases, p38/MAPK and JNK, in a time-dependent manner, and decreased HSG cell viability. Western blotting of LC3B-II and p62 in both normal and autophagic flux-administered conditions revealed elevated autophagy upon TLR9 activation. Observing the cell cytoplasm through transmission electron microscopy and mRFP-GFP-LC3B-tagged fluorescence confirmed an increased number of autophagosomes and autolysosomes in TLR9-activated cells. Bax/Bcl-2 ratio calculations, caspase-3 activity assays and Hoechst nuclear staining were utilized to confirm the involvement of apoptosis in TLR9 signaling activation. Furthermore, we selected SB239063, a p38/MAPK signaling inhibitor, and SP600125, a JNK inhibitor, to identify the functions of p38/MAPK and JNK in TLR9-mediated signaling transduction. Multiple approaches, including Western blotting assays, fluorescence assessments and caspase-3 activity measurements, confirmed that inhibition of p38/MAPK signaling ameliorated both autophagy and apoptosis in TLR9-activated HSG cells, whereas inhibition of JNK signaling attenuated apoptosis but failed to modulate autophagy in the models mentioned above. Our results indicate a divergent function of p38/MAPK and JNK in TLR9-mediated autophagy and apoptosis in salivary gland cells.

Juvenile recurrent parotitis: Soft foods contribute to the delayed development of salivary glands.

BACKGROUND: Juvenile recurrent parotitis (JRP) is the second-most common childhood disease of the salivary glands after mumps. Since popularisation of mumps vaccination, children suffered from JRP more often, and the aetiology remains unclear. Chinese children had the habit of soft foods due to the special dietary habit of Asia. OBJECTIVES: To clarify whether mastication was related to the pathogenesis of JRP and whether the growth of salivary glands was influenced by soft diet. METHODS: Investigation of dietary habit and masticatory efficiency from 2015 to 2018 of children diagnosed with JRP compared with the normal children by the dentition. Mice had been fed a soft diet beginning in their development phase. The gland weight, amount of saliva, salivary amylase, histological and ultrastructural observation and the expression levels of EGF, FGFr2 and Wnt3a had been tested. RESULTS: The JRP children preferred soft foods and had a significantly lower masticatory efficiency than do normal children. When normalised by body weight, the gland weight, amount of saliva and amount of salivary amylase in the experimental group were significantly lower. The ultrastructural results showed that the acinar cells in the experimental groups were smaller and contained fewer electron-dense secretory granules than those in the control groups. The expression levels of EGF, FGFr2 and Wnt3a in the salivary glands of mice in the experimental groups were significantly lower than those of mice in the control groups. CONCLUSION: The soft diet indeed influenced the salivary gland through insufficient mastication, which could be one of the primary factors inducing JRP.

Prediction Model of Cardiac Risk for Dental Extraction in Elderly Patients with Cardiovascular Diseases.

BACKGROUND: With the rapidly increasing population of elderly people, dental extraction in elderly individuals with cardiovascular diseases (CVDs) has become quite common. The issue of how to assure the safety of elderly patients with CVDs undergoing dental extraction has perplexed dentists and internists for many years. And it is important to derive an appropriate risk prediction tool for this population. OBJECTIVES: The aim of this retrospective, observational study was to establish and validate a prediction model based on the random forest (RF) algorithm for the risk of cardiac complications of dental extraction in elderly patients with CVDs. METHODS: Between August 2017 and May 2018, a total of 603 patients who fulfilled the inclusion criteria were used to create a training set. An independent test set contained 230 patients between June 2018 and July 2018. Data regarding clinical parameters, laboratory tests, clinical examinations before dental extraction, and 1-week follow-up were retrieved. Predictors were identified by using logistic regression (LR) with penalized LASSO (least absolute shrinkage and selection operator) variable selection. Then, a prediction model was constructed based on the RF algorithm by using a 5-fold cross-validation method. RESULTS: The training set, based on 603 participants, including 282 men and 321 women, had an average participant age of 72.38 ± 8.31 years. Using feature selection methods, 11 predictors for risk of cardiac complications were screened out. When the RF model was constructed, its overall classification accuracy was 0.82 at the optimal cutoff value of 18.5%. In comparison to the LR model, the RF model showed a superior predictive performance. The AUROC (area under the receiver operating characteristic curve) scores of the RF and LR models were 0.83 and 0.80, respectively, in the independent test set. The AUPRC (area under the precision-recall curve) scores of the RF and LR models were 0.56 and 0.35, respectively, in the independent test set. CONCLUSION: The RF-based prediction model is expected to be applicable for preoperative clinical assessment for preventing cardiac complications in elderly patients with CVDs undergoing dental extraction. The findings may aid physicians and dentists in making more informed recommendations to prevent cardiac complications in this patient population.

Functional surgery for the treatment of dentigerous cyst in the maxillary sinus.

BACKGROUND: Dentigerous cyst (DC) in the maxillary sinus is rarely seen. Several complications are observed after the Caldwell-Luc operation, which is combined with endoscopy. Still, a more perfect treatment method is yet to be discovered. OBJECTIVES: The purpose of this study was to explore and assess a new functional surgical treatment with fewer complications, which not only insured normal maxillary sinus cilia restoration and bony integrity but also did little damage to maxillary sinus natural ostium. METHODS: Dentigerous cyst in the maxillary sinuses of 20 patients had conditions diagnosed through radiographic imaging and the locating of bone windows' positions according to preoperative 3-dimensional computed tomography (CT) (3D CT). All the patients underwent a functional surgery in which a bony lid was created anteriolaterally of maxillary sinus with piezosurgery and reimplanted by titanium plates after enucleating the cyst, leaving the maxillary sinus mucosa in place with or without endoscope's assistance. Therapeutic efficacy was evaluated by clinical examination and radiographic imaging at regular intervals; the longest follow-up was 24 months. RESULTS: All the patients recovered except for one, who underwent plate removal and radical maxillary sinusotomy owing to infection. Patients were asymptomatic, and CT images showed integrated maxillary bone. Extrusion deformation of the sinus was improved to different extents after 6 to 24 months of follow-up. CONCLUSIONS: Functional surgery for the treatment of DC in the maxillary sinus is a new approach and has the advantages of less surgical trauma, restoration of mucosa and bony wall, and more satisfactory results.

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

BACKGROUND: An 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 Sjögren's syndrome (pSS) who were not receiving medications and to examine the correlations between these miRNA levels and the clinical features of the disease. METHOD: Using 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. RESULTS: Compared with the healthy controls, the miR-146a expression level was significantly increased in the patients with pSS (P = 0.0182) and was positively correlated with the VAS scores for parotid swelling (r = 0.4475, P = 0.0192) and dry eyes (r = 0.4051, P = 0.0361). Although the miR-155 expression level was significantly decreased in the patients with pSS (P = 0.0131), the miR-155 expression positively correlated with the VAS score for dry eyes (r = 0.4894, P = 0.0096). CONCLUSION: Our 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.

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

OBJECTIVE: The 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 Sjögren's syndrome (pSS) in NOD/Ltj mouse, aiming to identify an ideal target therapy model for human pSS. METHODS: NOD/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. RESULTS: The 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 5 weeks, peaked at 8 weeks and then gradually decreased at 10 weeks, 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. CONCLUSIONS: From 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.

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.

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

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.

Comparison of disc position stability and condylar bone remodelling between two open disc repositioning surgeries: a retrospective single-centre cohort study.

BACKGROUND AND OBJECTIVE: Open suturing (OSu) and mini-screw anchor (MsA) are two commonly used open disc repositioning surgeries for anterior disc displacement (ADD) of the temporomandibular joint (TMJ). This study assesses the differences in disc position stability (DPS) and condylar bone remodelling (CBR) between these two surgical procedures in a single centre. METHODS: A retrospective cohort study using MRI scans (pre-operation, 1 week and 12 months post-operation) of all patients who had open TMJ disc repositioning surgery from January 2016 to June 2021 at one centre through two surgical techniques (OSu and MsA) was performed. The predictor variable was technique (OSu and MsA). Outcome variables were DPS and CBR. During follow-up, DPS was rated as good, acceptable and poor, and CBR was graded as improved, unchanged, and degenerated. Multivariate analysis was used to compare the DPS and CBR at 12 months after adjusting five factors including age, sex, Wilkes stage, preoperative bone status (normal, mild/moderate abnormal) and the degree of disc repositioning (normal, overcorrected, and posteriorly repositioned). Relative risk (RR) for DPS and CBR was calculated by multivariate logistic regression. RESULTS: Three hundred eighty-five patients with 583 joints were included in the study. MRIs at 12 months showed that 514 joints (93.5%) had good DPS, and 344 joints (62.5%) had improved CBR. Multivariate analysis revealed that OSu had higher DPS (RR=2.95; 95% CI, 1.27-6.85) and better CBR (RR=1.58; 95% CI, 1.02-2.46) than MsA. Among the factors affecting DPS, females had better results than males (RR=2.63; 95% CI, 1.11-6.26) and overcorrected or posteriorly repositioned discs were more stable than normally repositioned discs (RR=5.84; 95% CI, 2.58-13.20). The improvement in CBR decreased with age increasing (RR=0.91; 95% CI, 0.89-0.93). Preoperative mild/moderate abnormal bone status had a higher probability of improved CBR compared to normal preoperative bone status (RR=2.60; 95% CI, 1.76-3.83). CONCLUSION: OSu had better DPS and CBR than MsA. Sex and the degree of disc repositioning impacted DPS, while age and preoperative bone status affected CBR.

Integrated analysis of m6A regulator-mediated RNA methylation modification patterns and immune characteristics in Sjögren's syndrome.

The epigenetic modifier N6-methyladenosine (m6A), recognized as the most prevalent internal modification in messenger RNA (mRNA), has recently emerged as a pivotal player in immune regulation. Its dysregulation has been implicated in the pathogenesis of various autoimmune conditions. However, the implications of m6A modification within the immune microenvironment of Sjögren's syndrome (SS), a chronic autoimmune disorder characterized by exocrine gland dysfunction, remain unexplored. Herein, we leverage an integrative analysis combining public database resources and novel sequencing data to investigate the expression profiles of m6A regulatory genes in SS. Our cohort comprised 220 patients diagnosed with SS and 62 healthy individuals, enabling a comprehensive evaluation of peripheral blood at the transcriptomic level. We report a significant association between SS and altered expression of key m6A regulators, with these changes closely tied to the activation of CD4+ T cells. Employing a random forest (RF) algorithm, we identified crucial genes contributing to the disease phenotype, which facilitated the development of a robust diagnostic model via multivariate logistic regression analysis. Further, unsupervised clustering revealed two distinct m6A modification patterns, which were significantly associated with variations in immunocyte infiltration, immune response activity, and biological function enrichment in SS. Subsequently, we proceeded with a screening process aimed at identifying genes that were differentially expressed (DEGs) between the two groups distinguished by m6A modification. Leveraging these DEGs, we employed weight gene co-expression network analysis (WGCNA) to uncover sets of genes that exhibited strong co-variance and hub genes that were closely linked to m6A modification. Through rigorous analysis, we identified three critical m6A regulators - METTL3, ALKBH5, and YTHDF1 - alongside two m6A-related hub genes, COMMD8 and SRP9. These elements collectively underscore a complex but discernible pattern of m6A modification that appears to be integrally linked with SS's pathogenesis. Our findings not only illuminate the significant correlation between m6A modification and the immune microenvironment in SS but also lay the groundwork for a deeper understanding of m6A regulatory mechanisms. More importantly, the identification of these key regulators and hub genes opens new avenues for the diagnosis and treatment of SS, presenting potential targets for therapeutic intervention.

Lysine acetyltransferase 6A maintains CD4+ T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity.

Augmented CD4+ T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4+ T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4+ T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4+ T cell subsets in vitro, and mice with KAT6A-deficient CD4+ T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis. Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatin where several glycolytic genes are located, thus affecting glucose metabolic reprogramming and subsequent CD4+ T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse models shows high therapeutic value for targeting KAT6A in autoimmunity. Our study provides novel insights into the epigenetic programming of immunometabolism and suggests potential therapeutic targets for patients with autoimmunity.

Different lymphoproliferative disorders in different salivary glands of primary Sjögren syndrome.

We report 1 case of primary Sjögren syndrome that showed histologic variation and different lymphoproliferative disorders in different salivary glands.Different salivary glands can show a different transition situation with histologic variation and lymphoproliferative disorders. The larger salivary glands have more potentially progressive transition situation than smaller glands. These findings also supported the theory that the transition of reactive B cells from lymphoepithelial sialadenitis to monoclonal lymphoma is generally a multistep process in different salivary glands within 1 person.