S-nitrosylation of Hsp90 promotes cardiac hypertrophy in mice through GSK3ß signaling.

Cardiac hypertrophy, as one of the major predisposing factors for chronic heart failure, lacks effective interventions. Exploring the pathogenesis of cardiac hypertrophy will reveal potential therapeutic targets. S-nitrosylation is a kind of posttranslational modification that occurs at active cysteines of proteins to mediate various cellular processes. We here identified heat shock protein 90 (Hsp90) as a highly S-nitrosylated target in the hearts of rodents with hypertrophy, and the role of Hsp90 in cardiac hypertrophy remains undefined. The S-nitrosylation of Hsp90 (SNO-Hsp90) levels were elevated in angiotensin II (Ang II)- or phenylephrine (PE)-treated neonatal rat cardiomyocytes (NRCMs) in vitro as well as in cardiomyocytes isolated from mice subjected to transverse aortic constriction (TAC) in vivo. We demonstrated that the elevated SNO-Hsp90 levels were mediated by decreased S-nitrosoglutathione reductase (GSNOR) expression during cardiac hypertrophy, and delivery of GSNOR adeno-associated virus expression vectors (AAV9-GSNOR) decreased the SNO-Hsp90 levels to attenuate cardiac hypertrophy. Mass spectrometry analysis revealed that cysteine 589 (Cys589) might be the S-nitrosylation site of Hsp90. Delivery of the mutated AAV9-Hsp90-C589A inhibited SNO-Hsp90 levels and attenuated cardiac hypertrophy. We further revealed that SNO-Hsp90 led to increased interaction of glycogen synthase kinase 3ß (GSK3ß) and Hsp90, leading to elevated GSK3ß phosphorylation and decreased eIF2Bε phosphorylation, thereby aggravating cardiac hypertrophy. Application of GSK3ß inhibitor TWS119 abolished the protective effect of Hsp90-C589A mutation in Ang II-treated NRCMs. In conclusion, this study demonstrates a critical role of SNO-Hsp90 in cardiac hypertrophy, which may be of a therapeutic target for cardiac hypertrophy treatment.

Myringoplasty With an Ultrathin Cartilage-Perichondrium Complex Graft Versus Temporalis Fascia Graft: A Propensity Score-Matched Analysis.

OBJECTIVE: To compare endoscopic myringoplasty using the cartilage-perichondrium complex as a graft (test group) with temporalis fascia microscopic myringoplasty (control group). STUDY DESIGN: A retrospective cohort study. SETTING: Department of Otorhinolaryngology in a tertiary Chinese hospital. METHODS: Data were collected on patients between 2017 and 2019. To balance the baseline characteristics between groups, we performed a propensity score-matched analysis, and 44 patients were included in each group. Hearing improvement and eardrum closure rates were compared, and risk factors affecting them were analyzed. RESULTS: In the control and test groups, 90.90% and 86.36% of patients had a mean air-bone gap ≤20 dB after the surgery, respectively (P = .843). The air conduction (AC) threshold gain at each frequency was similar in the 2 groups (P > .05). The closure rates were 95.45% and 93.18%, respectively (P = .645). The air-bone gap improved significantly after surgery, F(1, 61) = 6.729, P = .012. Age, group, middle ear mucosal status, and location of the perforation did not affect the change in air-bone gap or the drum closure rate (P > .05). However, there was an interaction between the change in air-bone gap and the size of the perforation, F(1, 61) = 11.067, P = 0001. CONCLUSION: Endoscopic myringoplasty using a cartilage-perichondrium complex graft is comparable with traditional surgery. Age, location of the perforation, and middle ear mucosal status did not significantly affect the change in air-bone gap or the drum closure rate. A perforation size ≥50% was always associated with a better air-bone gap improvement.

Bioinformatics and immunohistochemistry analyses of expression levels and clinical significance of CXCL2 and TANs in an oral squamous cell carcinoma tumor microenvironment of Prophyromonas gingivalis infection.

The present study aimed to detect the immunoexpression and clinical significance of Porphyromonas gingivalis (P. gingivalis) in the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC). The immunoexpression of P. gingivalis in OSCC tissues was detected via immunohistochemistry (IHC) after P. gingivalis was infected into the TME of OSCC. To identify the differentially expressed genes in the carcinogenesis and progression of OSCC with P. gingivalis infection, microarray datasets (GSE87539 and GSE138206) were downloaded from the Gene Expression Omnibus database. The immunoexpression levels of C-X-C motif chemokine ligand 2 (CXCL2) and tumor-associated neutrophils (TANs) were also evaluated via IHC, and the immunoexpression levels of all three clinical variables were analyzed using χ2 or Fisher's exact tests. The survival rates were calculated using the Kaplan-Meier method and the survival curves were compared using log-rank tests. Predominantly strong immunoexpression of P. gingivalis was identified in OSCC samples. CXCL2 was considered to be a differential gene in the two datasets. Immunoexpression of P. gingivalis was positively associated with CXCL2 and TANs expression. Furthermore, P. gingivalis was associated with survival status (P<0.001) and differentiation (P<0.001). CXCL2 was associated with age (P=0.038) and survival status (P=0.003), while TANs were associated with T stage (P=0.015) and clinical stage (P=0.002). These clinical variables were considered to be independent risk factors for the poor prognosis of patients with OSCC. Collectively, the results suggested that the immunoexpression of P. gingivalis may be positively associated with CXCL2 and TANs. In addition, the strong immunoexpression levels of P. gingivalis, CXCL2 and TANs may be associated with a poor prognosis in patients with OSCC.

[Logistic regression analysis of risk factors of temporomandibular disorder in undergraduates of Xinjiang Medical University].

PURPOSE: To investigate the prevalence of temporomandibular disorders (TMD) in undergraduates of Xinjiang Medical University and analyse its possible risk factors. METHODS: A sample of 700 medical students included 244 males and 456 females was selected from Xinjiang Medical University and underwent examination of temporomandibular joint, questionnaire survey. Their average age was 20.08±1.457 years. Prevalence of TMD was analyzed, and the possible risk factors associated with the disease were identified by logistic regression analysis with SPSS17.0 software package. RESULTS: The prevalence of TMD was 42.40% in this population. There was no difference between different ethnics. Chewing-side preference, bruxism，orthodontic treatment，tooth extraction，psychological factors，anterior overjet, posterior scissors-bite were the main risk factors which increased the occurrence of TMD. CONCLUSIONS: Poor oral habits, psychological factors and malocclusion were related to the development of TMD.

Expression of the interleukin-21 and phosphorylated extracellular signal regulated kinase 1/2 in Kimura disease.

OBJECTIVE: To investigate the expressions of interleukin (IL)-21 and phosphorylated extracellular signal regulated kinase 1/2 (pERK1/2) in Kimura disease (KD) and to correlate the findings with clinical and prognostic variables. METHODS: Immunohistochemical analysis of IL-21 and pERK1/2 was performed in 18 cases of KD and five gender- and age-matched control samples. Clinical data were extracted and patients followed up for a mean period of 32.1 months. RESULTS: After a mean follow-up period of 32.1 months (range 1-102 months), recurrence was diagnosed as the end point for seven patients-that is, a 44% (7/16) cumulative recurrence rate. In comparison with gender- and age-matched controls, patients showed strong in situ expressions of IL-21 and pERK1/2, respectively (p<0.05). Patients with strong IL-21 staining intensity and overexpression of pERK1/2 had a lower recurrence rate than those with moderate staining intensity (p=0.049, p=0.019, respectively). However, differences were not statistically significant by gender, age, eosinophils, location, multiplicity, laterality, size, duration and primary outbreak. pERK1/2 was the independent prognostic factor (p=0.020), while age, gender, eosinophils, multiplicity, laterality, size, duration, primary outbreak and expression of IL-21 were not. CONCLUSIONS: This study suggests that the IL-21/pERK1/2 pathway is activated in KD, and pERK1/2 might be considered as a potential prognostic indicator in KD.

Kimura's disease: risk factors of recurrence and prognosis.

OBJECTIVES: The aim of this study was to evaluate risk factors for recurrence and prognosis of Kimura's disease. METHODS: In this study, 32 patients received surgery alone, surgery followed by steroids orally and surgery followed by radiotherapy respectively from 2003 to 2015 (male/female: 27/5, ages: 6-64 years). Retrieval of clinical data and follow-ups have been done. The clinical features used as variables include age, gender, location, multiplicity, laterality, size, duration, primary outbreak, smoking, eosinophils, systemic disease and remedies. Statistical analysis including Kaplan-Meier method, Fisher's exact test, Kruskal-Wallis H test, Mann-Whitney U-test and Cox proportional hazard regression model were performed with the SPSS 17.0. The threshold of statistical significance was set at P=0.05. RESULTS: Median recurrence time was 29 months (2.42 years) after discharged and 56.3% patients relapsed. High recurrence rate was significantly associated with smoking habit (P=0.036). Patients who were diagnosed systemic disease (P=0.027) and were treated with surgery alone (P=0.025) or surgery followed by steroids orally (P=0.025) had short disease-free time. Furthermore, smoking habit (HR=3.383, 95% CI: 1.213-9.433, P=0.02), systemic disease (HR=4.462, 95% CI: 1.443-13.794, P=0.009), surgery alone (HR=4.668, 95% CI: 1.506-14.470, P=0.008) and surgery followed by steroids orally (HR=6.053, 95% CI: 1.330-27.556, P=0.02) were identified as risk factors for the prognosis of Kimura's disease. CONCLUSIONS: Smoking habit, systemic diseases, surgery alone and surgery followed by steroids orally were associated with poor prognosis of Kimura's disease, and they might be prognostic markers of Kimura's disease.