TSG-6 Inhibits the NF-κB Signaling Pathway and Promotes the Odontogenic Differentiation of Dental Pulp Stem Cells via CD44 in an Inflammatory Environment.

In pulpitis, dentinal restorative processes are considerably associated with undifferentiated mesenchymal cells in the pulp. This study aimed to investigate strategies to improve the odonto/osteogenic differentiation of dental pulp stem cells (DPSCs) in an inflammatory environment. After pretreatment of DPSCs with 20 ng/mL tumor necrosis factor-induced protein-6 (TSG-6), DPSCs were cultured in an inflammation-inducing solution. Real-time polymerase chain reaction and Western blotting were performed to measure the expression levels of nuclear factor kappa B (NF-κB) and odonto/osteogenic differentiation markers, respectively. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to assess cell proliferation and activity. Subcutaneous ectopic osteogenesis and mandibular bone cultures were performed to assess the effects of TSG-6 in vivo. The expression levels of odonto/osteogenic markers were higher in TSG-6-pre-treated DPSCs than nontreated DPSCs, whereas NF-κB-related proteins were lower after the induction of inflammation. An anti-CD44 antibody counteracted the rescue effect of TSG-6 on DPSC activity and mineralization in an inflammatory environment. Exogenous administration of TSG-6 enhanced the anti-inflammatory properties of DPSCs and partially restored their mineralization function by inhibiting NF-κB signaling. The mechanism of action of TSG-6 was attributed to its interaction with CD44. These findings reveal novel mechanisms by which DPSCs counter inflammation and provide a basis for the treatment of pulpitis.

Knowledge, Attitude, Skill, and Practice of Emergency Nurses Regarding the Early Management of Patients With Acute Ischemic Stroke in Beijing.

INTRODUCTION: Emergency nurses play an important role in the early management of acute ischemic stroke. The purpose of this study was to evaluate the knowledge, attitudes, skills, and practice of emergency nurses in Beijing regarding the early management of acute ischemic stroke. METHODS: This cross-sectional study enrolled emergency nurses in 26 hospitals in Beijing between August and November 2022. Correlations among knowledge, attitude, and skill/practice were evaluated by Pearson correlation analysis. RESULTS: This study included 564 nurses (82.98% were female). The average knowledge, attitude, and skill/practice scores were 15.48 ± 2.39 (possible range, 0-22), 39.84 ± 4.89 (possible range, 9-45), and 40.59 ± 5.21 (possible range, 13-52). The knowledge was significantly positively correlated with attitude and skill/practice (all P< .001). There was also a positive correlation between attitude and skill/practice (P< .001). DISCUSSION: These findings may facilitate the implementation of education/training programs to improve the early management of acute ischemic stroke by nurses in emergency departments.

Oral mucosal lesions with transient self-healing of Langerhans cell histiocytosis: a case report.

Langerhans cell histiocytosis (LCH) is a group of unexplainable abnormal proliferation and aggregation of Langerhans cell. LCH can be classified into four clinical variants: Letterer-Siwe disease, Hand-Schüller-Christian disease, eosinophilic granuloma, and congenital self-healing LCH. LCH is most prevalent in children. Lesions can be localized in a single system or multiple organs, and clinical manifestations vary depending on the affected organs. The skin and mucocutaneous tissues are the starting point of the affected tissue. This study presents a LCH case characterized by transient self-healing. This case can further provide references for the clinical diagnosis and treatment of LCH.

Amyloidosis initially only manifesting as oral mucosal hemorrhagic lesions: a case series report.

Amyloidosis is a heterogeneous series of diseases associated with extracellular amyloid protein depositions, which can involve multiple organs and tissues, leading to tissue structure alterations and organ dysfunction. The tongue is the most frequently involved site of oral amyloidosis, and one of its characteristic clinical presentations is macroglossia. Here, we report 3 extremely rare cases of amyloidosis exclusively appearing as multiple blood blisters, petechiae, and ecchymoses of the oral mucosa, in the absence of common clinical manifestations of oral and systemic amyloidosis. In a word, we highlight the possibility of oral mucosal hemorrhagic lesions as the initial clinical signs of systemic amyloidosis and the significance of the early and timely diagnosis of amyloidosis.

Targeting Th17 cells: a promising strategy to treat oral mucosal inflammatory diseases.

With the improved quality of life, oral health is under increased pressure. Numerous common oral mucosal diseases, such as oral lichen planus(OLP) and gingivitis, are related to the destruction of the oral immune barrier. The cytokines secreted by T-helper 17 (Th17) cells are essential for maintaining oral immune homeostasis and play essential roles in immune surveillance. When antigens stimulate the epithelium, Th17 cells expand, differentiate, and generate inflammatory factors to recruit other lymphocytes, such as neutrophils, to clear the infection, which helps to maintain the integrity of the epithelial barrier. In contrast, excessive Th17/IL-17 axis reactions may cause autoimmune damage. Therefore, an in-depth understanding of the role of Th17 cells in oral mucosa may provide prospects for treating oral mucosal diseases. We reviewed the role of Th17 cells in various oral and skin mucosal systemic diseases with oral characteristics, and based on the findings of these reports, we emphasize that Th17 cellular response may be a critical factor in inflammatory diseases of the oral mucosa. In addition, we should pay attention to the role and relationship of "pathogenic Th17" and "non-pathogenic Th17" in oral mucosal diseases. We hope to provide a reference for Th17 cells as a potential therapeutic target for treating oral mucosal inflammatory disorders in the future.

Regulatory T cell therapy suppresses inflammation of oral mucosa.

Oral inflammatory diseases, including oral lichen planus (OLP) and recurrent aphthous ulcer (RAU), seriously affect the patient's quality of life. Due to the lack of ideal disease models, it is difficult to determine whether novel immunotherapy strategies are effective in treating oral inflammatory diseases. Here, we show that the deficiency of Foxp3 or IL-2 caused oral mucosa inflammation in mice, proving that Treg cells are important in maintaining the immune homeostasis in the oral mucosa. Then we determined that adoptive transfer of CD4+CD25-CD45Rbhigh T cells could induce oral inflammation in Rag1 -/- mice, and co-transfer of Treg cells together with CD4+CD25-CD45Rbhigh T cells could suppress the development of oral inflammation in this mouse model. Our study showed that adoptive transfer of CD4+CD25-CD45Rbhigh T cells into Rag1 -/- mice could be a novel disease model of oral inflammation. Our data provides direct evidence that Treg cell therapy is effective in suppressing oral mucosa inflammation in mice. Therefore, Treg cell therapy may be a promising novel strategy to treat oral inflammatory diseases.

Geographic Distribution of HCV Genotypes and Efficacy of Direct-Acting Antivirals in Chronic HCV-Infected Patients in North and Northeast China: A Real-World Multicenter Study.

Objective: To assess the geographic distribution of HCV genotypes, effectiveness, and safety of DAA treatment for HCV-infected patients in North and Northeast China. Methods: The geographic distribution of HCV genotypes was analyzed in 2162 patients recruited from April 2018 to February 2021. Sustained virologic response rates at 12 (SVR12) or 24 (SVR24) weeks posttreatment and safety were analyzed in 405 patients who completed DAA treatment according to patient baseline characteristics and treatment. Results: Four genotypes and six subtypes were identified as follows: 1b (1187, 54.90%), 2a (790, 36.54%), 3a/b (134, 6.20%), 6a/n (44, 2.04%), mixed genotypes (2a-6a or 2a-3a) (7, 0.32%). Overall, 99.01% patients achieved SVR12, while 98.43% achieved SVR24. All patients treated with elbasvir/grazoprevir (EBR/GZR), sofosbuvir/velpatasvir ± ribavirin (SOF/VEL ± RBV), and SOF/ledipasvir (LDV) achieved SVR12 or SVR24; 92.86% SVR12 and 95.83% SVR24 were observed in patients using SOF + RBV. SVR12 was higher in noncirrhosis versus compensated cirrhosis patients (100% vs. 97.09%, p=0.022). No severe drug-related adverse event was observed. Conclusions: Genotypes 1b and 2a were dominant subtypes in North and Northeast China. The approved drug regimens EBR/GZR and SOF/LDV for subtype 1b and SOF/VEL for nongenotype 1b are the optimal effective and safety profile.

Identification of potential plasma markers for hepatitis B virus-related chronic hepatitis and liver fibrosis/cirrhosis.

The aim of this study was to identify potential plasma biomarkers for hepatitis B virus (HBV)-related liver diseases. High-throughput transcriptome sequencing analysis was performed on five patients with chronic hepatitis B (CHB), five patients with HBV-associated liver fibrosis/liver cirrhosis (LF/LC), and four healthy participants. By short time-series expression miner and functional analysis, aquaporin 1 (AQP1), dystroglycan 1 (DAG1), and hemoglobin subunit beta (HBB) were identified as potential biomarkers. Immunohistochemical analysis revealed that the expression levels of AQP1, DAG1, and HBB were upregulated in the three groups. Subsequent enzyme-linked immunosorbent assay tests on the training cohort (n = 150) indicated that the plasma levels of AQP1 and DAG1 were highest in LF/LC patients, followed by those in CHB patients, and the lowest in healthy controls. APAD model, a diagnostic panel incorporating age, platelet, AQP1, and DAG1 levels, exhibited the strongest stratification ability to distinguish LF/LC patients from CHB patients, and to differentiate CHB patients from healthy controls. Furthermore, the diagnostic accuracies of the biomarkers and APAD model were verified in an independent cohort consisting of 230 participants. In conclusion, both AQP1 and DAG1 have good diagnostic values and APAD model greatly enhances the diagnostic accuracy for HBV-related hepatic diseases.

Plasma YAP1 predicts esophageal varices and the risk of variceal bleeding in liver cirrhosis.

Aim: To explore the predictive value of plasma YAP1 for esophageal varices (EV) and high-risk EV (HRV) in patients with liver cirrhosis. Materials & methods: A total of 208 patients with liver cirrhosis were enrolled and categorized into four groups. Correlation analysis, logistic regression analysis and receiver operating characteristic curve analysis were performed to evaluate the diagnostic performance of plasma YAP1 for EV and HRV. Results: Plasma YAP1 levels were significantly elevated with the occurrence and progression of EV in cirrhotic patients. The multivariate logistic regression analysis revealed that plasma YAP1 is an independent predictor for EV and HRV. For predicting EV and HRV, the YAP1 cut-off values of 5.43 and 6.98 ng/ml yielded the area under the receiver operating characteristic curves of 0.944 and 0.955, respectively. Conclusion: Plasma YAP1 is a potential novel noninvasive biomarker for predicting EV and HRV in patients with liver cirrhosis.