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.

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.

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 Spearman's 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.

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.

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.

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.

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.

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.

A retrospective case series illustrating a possible association between a widened hilum and sialolith formation in the submandibular gland.

OBJECTIVE: The purpose of this study was to explore any association between anatomical variances in the ductal system and sialolith formation using sialoendoscopy and acrylic resin replication of the ductal system. METHODS: A retrospective study of 372 submandibular gland sialoendoscopies was performed to review the findings of the submandibular gland duct anatomy. Using sialoendoscopy and replicated casts, a high rate of hilar widening was noted in patients with submandibular sialolithiasis. RESULTS: Sialolithiasis was detected in 326 of the patients who presented with obstructive symptoms. Around 67% (285/426) of the stones were located in the distal third of the ducts or at the hilum of the submandibular gland. During the sialoendoscopic procedure, the anatomy of the ductal system was examined and 285/326 (87.4%) of the hilums were noted to be widened like a basin. The anatomy of the duct from the replicated casts demonstrated a treelike structure and the basin-like widening of the hilum was found in all the excised submandibular glands. CONCLUSION: Using sialoendoscopy, a high number of patients presenting with sialolithiasis in the submandibular gland seem to have an anatomical variance in the hilar region. The reproduced ductal system from excised glands also demonstrated this abnormal widening of the hilum. Although further studies need to be performed, we try and explain why there is such a high prevalence of hilar widening in patients with submandibular sialolithiasis.

Anatomic relationship between impacted third mandibular molar and the mandibular canal as the risk factor of inferior alveolar nerve injury.

Our aim was to explore the relation between the site of the mandibular canal and neurosensory impairment after extraction of impacted mandibular third molars. We organised a retrospective study of 537 extractions in 318 patients in which the affected tooth was intersected by the mandibular canal. This was verified by cone-beam computed tomography (CBCT), and we analysed the relation between the site of the canal and the likelihood of injury to the inferior alveolar nerve (IAN) after extraction of the third molar. The relation between the position of the root of the tooth and the mandibular canal was categorised into 4 groups: I=root above the canal; II=on the buccal side; III=on the lingual side; and IV=between the roots. The overall rate of neurosensory impairment after extraction was 6% (33/537). It occurred in 9/272 patients (3%) in group 1, 16/86 (19%) in group II, and in 8/172 (5%) in group III. There was no neurosensory impairment in group IV where the canal was between the roots. There were significant differences between group II and groups I and III (p<0.01), but not between groups I and III (p=0.32). The risk of damage to the inferior alveolar nerve is increased if third molars intersect with the mandibular canal, particularly on its buccal side.

Clinicopathologic features of dentigerous cysts in the maxillary sinus.

Dentigerous cyst (DC) in the maxillary sinus is extremely rare. This study evaluated the clinical features, etiologic factors, imaging, treatment, and signs and symptoms of this type of DC. Clinical symptoms, radiographic findings, surgical methods, and histopathologic findings of 4 patients with DCs in the maxillary sinus were evaluated. In addition, we reviewed the literature reports of DCs in the maxillary sinus over the past 40 years. Our 4 patients with DC in the maxillary sinus showed the following results: (1) all the patients were males at first 3 decades of age, (2) swelling and/or yellow-green pus discharges from pharyngeal cavity were common symptoms, (3) the involved teeth in the DC were the maxillary third molar teeth and supernumerary teeth, and (4) Caldwell-Luc approach was performed in these 4 patients. The patients with DC in the maxillary sinus should be evaluated thoroughly by extraoral and intraoral examinations, proper diagnostic imaging procedures, and pathologic examination to avoid misdiagnosis of maxillary sinusitis. The standard treatment for DC in the maxillary sinus is often removed by Caldwell-Luc approach. Furthermore, marsupialization or functional endoscopic sinus surgery may be performed because of the size, location of the cysts, or the age of the patients.

Dentigerous cysts associated with impacted supernumerary teeth in the anterior maxilla.

Dentigerous cysts are thought to be caused by a developmental abnormality derived from the reduced enamel epithelium of the tooth forming organ. Most typical dentigerous cysts are those associated with the third molar teeth of the mandible, but rarely involve impacted supernumerary teeth in the anterior maxilla. Swelling and/or pain may be the major complaints of the patients. Herein, we review the literature spanning the past 22 years concerning dentigerous cysts associated with supernumerary teeth in the anterior maxilla, and present four additional cases with emphasis given to the clinicopathological characteristics of this type of dentigerous cyst.

[The expression of interferon-alpha in peripheral blood of patients with primary Sjogren's syndrome].

PURPOSE: To investigate the interferon-alpha level in peripheral blood of patients with primary Sjogren's syndrome (pSS), and explore preliminarily the correlation between pSS and interferon-alpha. METHODS: ELISA and real-time PCR were used to evaluate the interferon-alpha level in peripheral blood in 37 patients with pSS and 24 patients with non-pSS. Statistical analysis was performed by Student's t test or Fisher's exact test using SAS6.12 software package. RESULTS: The results demonstrated that 43.24% (16/37) patients with pSS had detectable IFN-alpha concentration in plasma (>or=12.5 pg/mL), the other 21 patients (56.76%) with pSS had undetectable IFN-alpha concentration(<12.5 pg/mL). All 24 controls had undetectable IFN-alpha expression.There was significant difference between the two groups(P=7.02 x 10(-5)). Furthermore, the mRNA expression levels of IFN-alpha gene in peripheral blood cells were over-expressed in patients with pSS(P=0.0124). CONCLUSIONS: The study reveals that interferon-alpha level in peripheral blood with pSS patients is overexpressed.

[The value of imaging methods in diagnosis of submandibular gland diseases].

PURPOSE: To retrospectively analyze the advantages and disadvantages of imaging methods commonly used for diagnosis of gland submandibular diseases. METHODS: One hundred and eighty-two patients with submandibular gland surgery were retrospectively studied to compare the accuracy rate between preoperative imaging and postoperative diagnosis.The data were analyzed using SAS8.0 software package.Fisher's exact test was used to compare the difference between B type ultrasonography, CT and MRI. RESULTS: Compared with postoperative pathological results,diagnostic accuracy rate of B type ultrasonography, CT and X-ray was 85.34%, 79.66% and 92.31%, respectively. MRI had a higher accuracy rate than B type ultrasonography or CT.(P<0.05). CONCLUSION: B type ultrasonography, CT and X-ray examination have misdiagnosis especially in submandibular sialadenitis,which is one of the most important causes of misdiagnosis leading to excision of the glands.MRI has higher application value in diagnosis of submandibular gland diseases.

[Diagnostic value of magnetic resonance sialography for submandibular sialolithiasis].

PURPOSE: To evaluate the role of MR Sialography(MRS) in diagnosis of submandibular sialolithiasis. METHODS: Twenty-one patients with submandibular sialolithiasis were scanned by MRS, the results of MRS were compared with those after proper treatment. RESULTS: The results of MRS were consistent with those after proper treatment. CONCLUSION: MRS has high diagnostic accuracy in diagnosis of sialolithiasis including submandibular sialadenitis.

[The value of MRS in diagnosis of Sjoigren's syndrome in parotid gland].

PURPOSE: The purpose of this study is to evaluate the value of MR sialography in diagnosis of Sjoigren's syndrome in parotid gland. METHODS: MRI and MRS were used to diagnose Sjoigren's symdrome and differentiate with other disease combined with clinical, serologic and histopathologic result. Meanwhile, the result of MRS was compared with sialograph. RESULTS: 25 cases were ultimately diagnosed as Sjoigren's syndrome among 32 cases by clinical, serologic, histopathologic and sialography or MRS method. 23 cases were presented typical image in MRS, and sensitivity was 92%; specificity 71.4% and accuracy 87.5%. Other different manifestations were found in 25 cases, such as: autoantibody 68%, focui lymphocytic infiltration 72%. 18 cases have the positive results between MRS and sialography and 15 cases (83.3%) have the same manifestations by degree classification. CONCLUSION: The Sjoigren's syndrome can be confirmed by clinical, serologic, histopathologic, and MRS or sialography. MRS is a reliable method to diagnosis and differentiated diagnose Sjoigren's syndrome with other disease.

[Clinical study of SS syrup in treating xerostomia].

OBJECTIVE: To compare the clinical efficacy of SS syrup, a Chinese medicine, and pilocarpine in treating patients with xerostomia. METHODS: Thirty-eight patients conformed to the inclusive criteria were randomly divided into two groups, they were treated by SS syrup (SS group) and pilocarpine (control group) respectively. Three indexes, i.e. questionnaire of dryness in mouth, total static salivary flow and dynamic salivary flow, before treatment, 1, 2 and 4 weeks after treatment were recorded and statistically analyzed. RESULTS: Significant difference was shown in the 3 indexes in the SS group between before treatment and 1, 2 and 4 weeks after treatment (P < 0.05), while in the control group significant difference was shown between before treatment and 1, 2, and 4 weeks after treatment except for total dynamic salivary flow after I weck treatment (P < 0.05). CONCLUSION: SS syrup, which has no adverse reaction, no contraindication, could be taken chronically, and shows good efficacy in improving the symptoms of xerostomia.

[The diagnostic value of magnetic resonance sialography for chronic obstructive parotitis].

PURPOSE: To evaluate the diagnostic value of magnetic resonance sialography (MRS) for chronic obstructive parotitis (COP). METHODS: 18 patients with COP underwent both conventional sialography and MRI sialography. A new magnetic resonance technique was applied. In addition to the usually performed T1 and T2 cross-sectional sequence, a heavy T2-weighted sequence (TR=4000 msec,TE=250 msec)was performed that allowed depiction of the fluid-filled parotid duct system. The MRI sialographic findings were compared with that of conventional sialography. The overall accuracy of diagnosis and ductal stenosis were assessed. RESULTS: The main duct of the parotid gland as well as primary branching ducts could be reliably depicted. Compared with the conventional sialography, the diagnostic accuracy of MRS was 94.4%(17/18) and stenosis diagnosis reached 100%(17/17). CONCLUSIONS: Initial experience indicates that magnetic resonance sialography can be applied successfully to investigate the duct system of the parotid gland. It is completely noninvasive and a promising alternative to radiographic sialography.