IgE directly affects eosinophil migration in chronic rhinosinusitis with nasal polyps through CCR3 and predicts the efficacy of omalizumab.

BACKGROUND: Whether IgE affects eosinophil migration in chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unclear. Moreover, our understanding of local IgE, eosinophils, and omalizumab efficacy in CRSwNP remains limited. OBJECTIVE: We investigated whether IgE acts directly on eosinophils and determined its role in omalizumab therapy. METHODS: Eosinophils and their surface receptors were detected by hematoxylin and eosin staining and flow cytometry. IgE and its receptors, eosinophil peroxidase (EPX), eosinophilic cationic protein, and CCR3 were detected by immunohistochemistry and immunofluorescence. Functional analyses were performed on blood eosinophils and polyp tissues. Logistic regression was performed to screen for risk factors. Receiver operating characteristic curve was generated to evaluate the accuracy. RESULTS: Both FcεRI and CD23 were expressed on eosinophils. The expression of FcεRI and CD23 on eosinophil in nasal polyp tissue was higher than in peripheral blood (both P < .001). IgE and EPX colocalized in CRSwNP. IgE directly promoted eosinophil migration by upregulating CCR3 in CRSwNP but not in healthy controls. Omalizumab and lumiliximab were found to be effective in restraining this migration, indicating CD23 was involved in IgE-induced eosinophil migration. Both IgE+ and EPX+ cells were significantly reduced after omalizumab treatment in those who experienced response (IgE+ cells, P = .001; EPX+ cells, P = .016) but not in those with no response (IgE+ cells, P = .060; EPX+ cells, P = .151). Baseline IgE+ cell levels were higher in those with response compared to those without response (P = .024). The baseline local IgE+ cell count predicted omalizumab efficacy with an accuracy of 0.811. CONCLUSIONS: IgE directly promotes eosinophil migration, and baseline local IgE+ cell counts are predictive of omalizumab efficacy in CRSwNP.

Endotypes of chronic rhinosinusitis based on inflammatory and remodeling factors.

BACKGROUND: Previous studies on the endotyping of chronic rhinosinusitis (CRS) that were based on inflammatory factors have broadened our understanding of the disease. However, the endotype of CRS combined with inflammatory and remodeling features has not yet been clearly elucidated. OBJECTIVE: We sought to identify the endotypes of patients with CRS according to inflammatory and remodeling factors. METHODS: Forty-eight inflammatory and remodeling factors in the nasal mucosal tissues of 128 CRS patients and 24 control subjects from northern China were analyzed by Luminex, ELISA, and ImmunoCAP. Sixteen factors were used to perform the cluster analysis. The characteristics of each cluster were analyzed using correlation analysis and validated by immunofluorescence staining. RESULTS: Patients were classified into 5 clusters. Clusters 1 and 2 showed non-type 2 signatures with low biomarker concentrations, except for IL-19 and IL-27. Cluster 3 involved a low type 2 endotype with the highest expression of neutrophil factors, such as granulocyte colony-stimulating factor, IL-8, and myeloperoxidase, and remodeling factors, such as matrix metalloproteinases and fibronectin. Cluster 4 exhibited moderate type 2 inflammation. Cluster 5 exhibited high type 2 inflammation, which was associated with relatively higher levels of neutrophil and remodeling factors. The proportion of CRS with nasal polyps, asthma, allergies, anosmia, aspirin sensitivity, and the recurrence of CRS increased from clusters 1 to 5. CONCLUSION: Diverse inflammatory mechanisms result in distinct CRS endotypes and remodeling profiles. The explicit differentiation and accurate description of these endotypes will guide targeted treatment decisions.

High expression of AP2M1 correlates with worse prognosis by regulating immune microenvironment and drug resistance to R-CHOP in diffuse large B cell lymphoma.

BACKGROUND: First-line treatment with R-CHOP has cured 50%-60% patients of diffuse large B cell lymphoma (DLBCL), and more than one-third patients will eventually progressed to relapsed/refractory disease with dismal outcomes. Adaptor Related Protein Complex 2 Subunit Mu 1 (AP2M1) is required for the activity of a vacuolar ATPase and may also play an important role in regulating the intracellular trafficking and function of CTLA-4 protein. Herein, using both public databases and our own tumor samples, we aimed to demonstrate the prognostic role of AP2M1 and the potential tumor-promoting mechanisms in DLBCL. METHOD: Using public datasets of DLBCL from both GEO and TCGA databases, we analyzed the role of AP2M1 in mediating chemoresistance to R-CHOP and its correlation with various clinical parameters and prognosis. By using various R packages, we evaluated the role of AP2M1 on regulating tumor immune microenvironment. Moreover, tumor samples of DLBCL from Beijing TongRen Hospital were used to validate our findings by immunohistochemistry staining. RESULT: Expression of AP2M1 was significantly increased in DLBCL, which was correlated with poor prognosis and a variety of clinical indicators. On the basis of enrichment analysis, it was found that AP2M1 may be related to intracellular receptor signaling pathway. Through immune analysis and drug prediction, we found that the expression of AP2M1 affected the immune environment and drug response of DLBCL, which further revealed the important role of AP2M1 in DLBCL. By analyzing 61 patients treated uniformly with R-CHOP regimen in our center, we validated the above findings that high expression of AP2M1 correlated with inferior survival outcomes and affected sensitivity to R-CHOP treatment. CONCLUSION: Expression of AP2M1 may affect the prognosis of DLBCL patients probably by affecting the immune environment and the responses to many drugs in treating DLBCL, indicating AP2M1 as a potential therapy target in DLBCL.

Automated and fast online method for simultaneously determining a broad spectrum of per- and polyfluoroalkyl substances in a small volume of cerebrospinal fluid.

Per- and polyfluoroalkyl substances (PFASs) are potentially neurotoxic compounds. Levels of PFASs in cerebrospinal fluid (CSF) could directly reflect their potential harm to the central nervous system. Because of the variety of PFASs and the rarity of CSF, there is an urgent need to establish a rapid online method to detect a broad spectrum of PFASs accurately and simultaneously by consuming a small amount of CSF. In this study, we developed a fast and automated method to analyze 52 PFASs in human CSF samples using online TurboFlow ultra-high-performance liquid chromatography-tandem mass spectrometry. Our method offered excellent matrix-matched standard curve linearity (correlation coefficient > 0.99), good limits of quantitation (MLOQs) (0.01 to 0.08 ng mL-1), satisfactory accuracy (recoveries of 74.6%-119.1%) and precision (relative standard deviations of 1.4%-13.2%), small sample amount consumption (50 µL), and fast analysis time (18 min per sample) without complex sample pretreatment procedures. These are advantageous for the high throughput screening of PFASs in environmental epidemiology studies. Repeated freeze-thaw experiments showed that it was better to perform the analytical process soon as possible after sample collection. The established method was used to analyze PFASs in 60 people. Short-chain PFASs, perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), and novel PFASs [sodium 2-(N-ethylperfluorooctane-1-sulfonamido)ethyl phosphate (SAmPAP), perfluoroethylcyclohexanesulfonate (PFECHS), and perfluoro-3, 7-dimethyloctanoic acid (P37DMOA)] were reported in CSF for the first time. PFBA and PFPeA were detected in all samples with mean concentrations of 0.24 and 0.22 ng mL-1, respectively. We also calculated the blood-brain barrier transmission efficiency of PFASs (RPFAS), and the mean RPFBA value was above 1, which indicated that PFBA might transfer from serum to CSF.

Investigation of the Value of T 2 Mapping in the Prediction of Eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

OBJECTIVES: Patients with eosinophilic chronic rhinosinusitis with nasal polyps (eosCRSwNP) usually have more extensive sinus disease, severe symptoms, and poorer disease control compared with patients with non-eosCRSwNP. Separating these entities will be crucial for patient management. The purpose of this study is to investigate T 1, T 2 , and apparent diffusion coefficient (ADC) values of the nasal polyps in patients with CRSwNP and evaluate the usefulness of these parameters for differentiating these diseases. METHODS: Sinonasal magnetic resonance imaging was performed in 36 patients with eosCRSwNP and 20 patients with non-eosCRSwNP (including T 1 mapping, T 2 mapping, and diffusion-weighted imaging) before surgery. The T 1 , T 2 , and ADC values were calculated and correlated with pathologically assessed inflammatory cells of nasal polyps. RESULTS: Significant higher T 2 value, higher eosinophil count, and lower lymphocyte count of the nasal polyps were observed in eosCRSwNP than those in non-eosCRSwNP. There was no significant difference in T 1 or ADC values between the 2 groups. T 2 value was correlated with eosinophil count and lymphocyte count in CRSwNP. The area under the curve of T 2 value for predicting eosCRSwNP was 0.78 with 89.9% sensitivity and 60.0% specificity. CONCLUSION: T 2 value is a promising imaging biomarker for predicting eosCRSwNP. It can help to distinguish eosCRSwNP from non-eosCRSwNP.

G6PC indicated poor prognosis in cervical cancer and promoted cervical carcinogenesis in vitro and in vivo.

BACKGROUND: The glucose-6-phosphatase catalytic subunit (G6PC) is a key enzyme that is involved in gluconeogenesis and glycogen decomposition during glycometabolism. Studies have shown that G6PC is abnormally expressed in various cancers and participates in the proliferation and metastasis of tumors. However, the role of G6PC in cervical cancer remains poorly established. METHODS: To analyze the expression of G6PC in cervical cancer tissues in patients by immunohistochemistry. Effects of G6PC deregulation on cervical cancer phenotype were determined using MTT, colony formation, transwell, and wound-healing assays. And constructed a nude mouse xenograft tumor model and CAM assay in vivo. The effect of G6PC on glycolysis in cervical cancer was also evaluated. Effect of G6PC on PI3K/AKT/mTOR pathway was detected by Western blot assay. RESULTS: In this study, G6PC expression was found to be upregulated in cervical cancer tissues, and this upregulated expression was associated with LN metastasis, clinical stage, recurrence, and disease-free survival and overall survival rates, indicating that G6PC could serve as a novel marker of early diagnosis in cervical cancer. G6PC promoted proliferation, invasion, epithelial mesenchymal transition (EMT) progression, and angiogenesis of cervical cancer cells. Mechanistically, G6PC activated PI3K/AKT/mTOR pathways. The PI3K/AKT pathway inhibitor, LY294002 could partially attenuate the effect. CONCLUSIONS: G6PC plays a key role in the progression of cervical cancer, and overexpressed G6PC is closely related to patient LN metastasis, clinical stage, recurrence and shortened survival. G6PC promoted cervical cancer proliferation, invasion, migration, EMT progression, and angiogenesis, partially through activating the PI3K/AKT pathway. G6PC, as a metabolic gene, not only plays a role in metabolism, but also participates in the development of cervical cancer. Its complex metabolic and non metabolic effects may be a potential therapeutic target and worthy of further study.

Quantitative parameters derived from 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging can accurately estimate the histologic grade of hypopharyngeal squamous cell carcinoma preoperatively.

PURPOSE: Among head and neck cancers, hypopharyngeal squamous cell carcinoma (HSCC) shows the highest malignancy, which is associated with histologic grading. This study was designed to investigate whether quantitative parameters derived from 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) can preoperatively estimate the histologic grade of HSCC. METHODS: 18F-FDG PET/MRI of neck was successfully performed in 21 patients with histologically proven HSCC including poorly differentiated group (ten patients) and well-moderately differentiated group (eleven patients). Quantitative parameters derived from FDG-PET, diffusion-weighted imaging (DWI), and dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) were calculated based on volume of interest drawn on the tumor and compared between two groups. The efficacy of quantitative parameters for the estimation of histologic grades of HSCC was evaluated. RESULTS: There were statistically significant differences in mean value of standard uptake value (SUV), apparent diffusion coefficient (ADC), and Ktrans derived from 18F-FDG PET/MRI of HSCC between two groups (p < 0.05). There was no statistically significant difference in other quantitative parameters derived from 18F-FDG PET/MRI of HSCC between two groups. The area under the curve (AUC) of the combination of SUVmean, ADCmean, and Ktrans in the estimation of histologic grade of HSCC was 0.936 with sensitivity of 90.0% and specificity of 81.8%. CONCLUSION: The combination of SUVmean, ADCmean, and Ktrans derived from 18F-FDG PET/MRI can accurately predict the histologic grade of HSCC preoperatively.

Serum immunoglobulin G4 has limited diagnostic value in immunoglobulin G4-related chronic rhinosinusitis.

PURPOSE: To investigate the profiles and factors influencing serum IgG4 levels and evaluate the diagnostic value of serum IgG4 in IgG4-related CRS. METHODS: This was a prospective study analyzing data from 288 hospitalized CRS patients who had undergone endoscopic sinus surgery from July 1, 2017 to August 31, 2018. Data were analyzed for correlations between elevated serum IgG4 concentrations (> 135 mg/dL) and clinical symptoms (nasal congestion, rhinorrhea, loss of smell, headache and/or facial pain), endoscopic presentation (Lund-Kennedy scores), allergic status (total and allergen-specific IgE), and pathological features (IgG4+ and IgG+ cells). RESULTS: Overall, 43/288 (14.9%) CRS patients had elevated serum IgG4 levels > 135 mg/dL. Comparison of the clinical parameters between patients with elevated and normal serum IgG4 levels demonstrated serum total IgE levels to be significantly different (P = 0.003) between the two groups; and significantly correlated with serum IgG4 level in CRS subjects (P = 0.000; r = 0.232), particularly CRS patients with nasal polyps (P = 0.000; r = 0.259). In contrast, the ratio of plasmocyte/inflammatory cells and IgG4+ cells/IgG+ plasmocytes, and IgG4+ plasma cells/HPF in sinus mucosa were not significantly different between the groups and no patient with elevated serum IgG4 demonstrated ratio of IgG4+ /IgG+ cells > 40% or > 10 IgG4+ plasma cells/HPF. CONCLUSION: Serum IgG4 concentration is not related to the clinical phenotype of CRS and is likely to be of limited value when used alone in the diagnosis of IgG4-related CRS.

Secretory carcinoma of the sinonasal cavity and pharynx: A retrospective analysis of four cases and literature review.

Secretory carcinoma (SC) is a recently recognized type of salivary gland tumor characterized by t(12;15) (p13;q25) translocation resulting in an ETV6-NTRK3 gene fusion. Most SCs are located in a main salivary gland, and primary sinonasal secretary carcinoma is rare. We describe three cases of primary SC in the sinonasal cavity with high-grade transformation (HGT) in one case, and the first case in the pharynx. All tumors comprised slightly atypical cells with solid, tubular, microcystic growth patterns. The case with HGT included two components with distinct sharp boundaries and comedo necrosis, high mitotic figures and obvious cellular atypia. Tumor cells were positive for vimentin, S100, and Gata-3 and negative for p63 and DOG-1. Three cases showed nuclear staining of pan-TRK and one showed cytoplasmic staining. All cases harbored ETV6 gene rearrangement, and ETV6-NTRK3 gene fusion was detected in three cases. Most patients were treated with radical resection and adjuvant therapy. After excision, all remained tumor-free for 65-164 months (medium 98.5 months). SC in the sinonasal cavity and pharynx is a low-grade malignant tumor with histologic features overlapping those of other salivary gland tumors. Immunohistochemical analysis and fluorescence in situ hybridization are useful techniques for its differential diagnosis.

Circular RNA dehydrodolichyl diphosphate synthase facilitated triple-negative breast cancer progression via miR-362-3p/DDX5 axis.

BACKGROUND: Triple-negative breast cancer (TNBC) is a common hypotype of breast cancer. Circular RNAs (circRNAs) are burgeoning serve as vital controllers in numerous tumors. Nevertheless, the expression and regulatory mode of circRNAs in TNBC are still indistinct. This paper aimed to reveal the function and molecular mechanism of circular RNA dehydrodolichyl diphosphate synthase (circDHDDS) in TNBC. METHODS: The contents of circDHDDS, DHDDS mRNA, microRNA-362-3p (miR-362-3p) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were executed to assess cell proliferation. The flow cytometry assay was utilized to detect cell apoptosis. The transwell assay and tube formation assay were applied to measure cell migration, invasion and angiogenesis. The targeted relationships of miR-362-3p and circDHDDS or DDX5 were forecasted and detected by dual-luciferase reporter assay. The in vivo test was implemented to confirm the effect of circDHDDS. RESULTS: The contents of circDHDDS and DDX5 were increased, and miR-362-3p level was decreased in TNBC. CircDHDDS deficiency reserved cell proliferation, migration, invasion and angiogenesis, while facilitated cell apoptosis in TNBC cells. Furthermore, miR-362-3p was validated to exert a tumor repressive effect in TNBC cells by suppressing DDX5. Moreover, DDX5 could regulate the development of TNBC. The experimental data exposed that levels of miR-362-3p presented noteworthy negative correlation with circDHDDS and DDX5, while circDHDDS and DDX5 exhibited significant positive correlation. In mechanism, circDHDDS bound to miR-362-3p to modulate DDX5 expression. In addition, circDHDDS knock-down also attenuated tumor growth. CONCLUSION: CircDHDDS expedited TNBC by swelling DDX5 via adapting miR-362-3p.

Changes in Clinical and Histological Characteristics of Nasal Polyps in Northern China over the Past 2-3 Decades.

INTRODUCTION: Recent studies have shown that inflammatory patterns of nasal polyps from patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) in East Asia have changed over time. However, to date there is a marked lack of similar data for CRSwNP in Northern China. This study thus aimed to assess the changes in the clinical and histological characteristics of CRSwNP patients from Northern China over the past 2-3 decades. METHODS: This was a retrospective study, which examined data from 2 groups of 150 CRSwNP patients each, who had undergone endoscopic sinus surgery in Beijing Tongren Hospital from 1993 to 1995 (group A) and from 2015 to 2019 (group B). All relevant data for demographic, clinical, and histological parameters were collected for each patient from the 2 groups and compared for overall changes between the 2 groups. RESULTS: The comorbidity of CRSwNP and asthma increased over time and the cellular phenotype of CRSwNPchanged significantly; in particular, the proportion of eosinophil-dominant CRSwNP increased, lymphocyte-dominant and plasma-dominant CRSwNP decreased significantly, and the proportions of neutrophil-dominant and mixed CRSwNP were not altered. The rate of polyp recurrence increased in CRSwNP but did not in eosinophilic CRSwNP. Smoking and age did not significantly impact the inflammatory patterns of CRSwNP. CONCLUSIONS: The inflammatory patterns of CRSwNP patients have changed and comorbidity of asthma significantly increased in CRSwNP patients in Northern China over the past 2-3 decades.

Sinonasal low-grade non-intestinal-type adenocarcinoma: A retrospective analysis and literature review.

Sinonasal low-grade non-intestinal-type adenocarcinomas (LG non-ITACs) are uncommon tumors with unclear histogenesis, although they are presumed to arise from seromucous glands or respiratory epithelium. We investigated the clinicopathological and immunohistochemical features of the tumors, with particular attention to the transition area from the normal epithelium to neoplastic cells and concurrent lesions; these features were compared with those of 10 patients with chronic sinusitis, who served as a control group. Seventeen patients with LG non-ITACs (17 tumors) were enrolled in this retrospective study (9 male patients and 8 female patients; mean age, 48 years [range, 16-74 years]). Tumor cells continuous with respiratory epithelium were detected in 10 tumors composed of a single layer of cells with papillary, tubular, or cystic growth pattern. The tumor cells were uniformly cuboidal to columnar and polar. In seven tumors without transition areas discerned, three tumors consisted of polygonal and flat cells with a solid, acinar, micropapillary and cribriform pattern. The others had the same morphology as those with transition areas. The tumor cells were positive for SOX10 (15/17), S100 protein (8/17), and CK7 (17/17). The normal epithelium connected to the respiratory epithelium was the terminal duct in the control group. Except for the lack of p63-positive cells, the immunophenotype and histomorphology of transition areas with LG non-ITACs were similar to those of the continuous areas between the terminal duct and the respiratory epithelium in the control group. LG non-ITACs are seromucinous tumors, some of which may originate from the terminal ducts of seromucinous glands.

Concomitant occurrence of Mikulicz's disease and immunoglobulin G4-related chronic rhinosinusitis: a clinicopathological study of 12 cases.

AIMS: Concomitant occurrence of Mikulicz's disease (MD) and immunoglobulin (Ig)G4-related chronic rhinosinusitis (IgG4-related CRS) is extremely rare. We evaluated the clinicopathological features of MD patients with concomitant IgG4-related CRS (CRS-MD). METHODS AND RESULTS: Twelve CRS-MD patients were evaluated clinically and biopsy samples were taken from the lacrimal/salivary glands (n = 12) and nasal mucosa (n = 7) for assessment of IgG4-positive cells, using immunohistochemical techniques. Similarly, nine MD patients and 10 patients with common CRS were evaluated as controls. CRS-MD patients had higher serum IgG and IgG4 concentrations than MD patients (P < 0.05 for both). Lymphoplasmacytic infiltration, lymphoid follicle formation and sclerosis was prominent in the lacrimal/salivary glands in both groups; however, the magnitude of IgG4-positive plasma cells infiltration in the CRS-MD group was significantly higher compared to the MD group (P = 0.004). Similarly, evaluation of nasal mucosa revealed greater lymphocyte, plasma cell and eosinophil infiltration and lymphoid follicle formation, together with significantly higher IgG4-positive plasma cell infiltration in the CRS-MD group compared to the common CRS group (P = 0.004). CONCLUSIONS: Concomitant MD and IgG4-related CRS were characterized by a combination of IgG4-positive plasma cells infiltration in the lacrimal/salivary glands and the nasal mucosa and increased serum IgG4.

Chondro-osseous respiratory epithelial adenomatoid hamartoma of the nasal cavity.

Chondro-osseous respiratory epithelial adenomatoid hamartoma is a rare hamartomatous lesion of the nasal cavity, with only five cases reported in the literature to date. We report the case of a 3-year-old boy who presented with nasal obstruction and a mass in the left nasal cavity. The mass was completely resected on endoscopy. On microscopy, hamartomatous proliferation of respiratory-type glands admixed with islands of immature hyaline cartilage, characteristic of chondro-osseous respiratory epithelial adenomatoid hamartoma, was seen. Neither local recurrence nor distant metastasis was observed after 6 month follow up. Recognition of chondro-osseous respiratory epithelial adenomatoid hamartoma as a benign lesion is important to avoid unnecessary surgical procedures.

Cellular phenotyping of chronic rhinosinusitis with nasal polyps.

BACKGROUND: Defining the phenotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) with prognosis may lead to delivery of personalized treatment. This study aimed to identify cellular phenotypes of CRSwNP using cluster analysis and define an algorithm for different clusters associated with polyp recurrence. METHODS: Overall, 366 patients with CRSwNP were enrolled in this retrospective analysis. Eighteen variables, including clinical characteristics and tissue/peripheral inflammatory cells assessments, were selected for factor analysis. Unsupervised cluster analysis was performed after variables reduction and standardization and differences in polyp recurrence during follow-up for a minimum of 24 months were analysed among clusters. Discriminant analysis was further used to develop a clinically useful algorithm for predicting clustering. RESULTS: Five phenotypic clusters were identified. Clusters 1 and 2 were plasma cell-dominant and lymphocyte-dominant phenotypes, respectively. Cluster 3 revealed a mixed inflammatory pattern. Cluster 4 was characterized by infiltration of predominantly neutrophils. Cluster 5 was characterized by a marked tissue eosinophilia and highest recurrence rate of 98.5%. The clinical algorithm predicted clustering with 93.7% accuracy. CONCLUSIONS: Chinese CRSwNP patients may be classified into five phenotypes with different polyp recurrence rates, based on the presence of predominantly plasma cells, lymphocytes, neutrophils, eosinophils or mixed inflammatory cells in polyps.

[IgG4-related sialodacryoadenitis and chronic rhinosinusitis: a clinicopathologic analysis of 13 cases].

OBJECTIVE: To study the clinicopathologic characteristics of IgG4-related sialodacryoadenitis and chronic rhinosinusitis (CRS). METHODS: A total of 13 patients (patient group) were evaluated clinically and biopsy specimens from the lacrimal/salivary glands (n=12) and nasal mucosa (n=8) were reviewed and immunohistochemistry was performed to assess IgG-and IgG4-positive cells. Similarly, nine patients with IgG4-related sialodacryoadenitis without CRS and 10 patients with common CRS were included as controls. RESULTS: There were 8 male patients and 5 female patients. The age of patients ranged from 32 to 71 years (mean 50.2 years). The patient group had higher serum IgG4 concentration than that of the control group (P<0.05). Lymphoplasmacytic infiltration, lymphoid follicle formation and sclerosis were prominent in lacrimal/salivary glands in both groups; however the magnitude of IgG4-positive plasmacytic infiltration in the patient group was significantly higher than that of the control group (P<0.05). Similarly, evaluation of nasal mucosa revealed greater lymphocytic and plasmacytic infiltration, and lymphoid follicle formation, together with significantly higher amount of IgG4-positive plasma cell infiltration in the patient group compared to the common CRS group (P<0.05). CONCLUSIONS: IgG4-related disease (IgG4-RD) simultaneously involving lacrimal/salivary glands and nasal cavity/paranasal sinuses is rare and characterized by a combination of IgG4-positive plasma cell infiltration involving lacrimal/salivary glands and nasal mucosa along with an increased serum level of IgG4. As a systemic disease, early and accurate diagnosis is therefore of great importance, and unnecessary surgery should be avoided.

NQO1 protein expression predicts poor prognosis of non-small cell lung cancers.

BACKGROUND: High-level expression of NAD(P)H: quinoneoxidoreductase 1 (NQO1) has been correlated with many types of human cancers, suggesting that NQO1 plays important roles in tumor occurrence and progression. This study attempted to explore the role of NQO1 in tumor progression and prognostic evaluation of non-small cell lung cancer (NSCLC). METHODS: Total 164 tissue samples, including 150 NSCLC paired with the adjacent non-tumor tissues and 14 normal lung tissues, were picked-up for immunohistochemical (IHC) staining of the NQO1 protein, and immunofluorescence (IF) staining was also performed to detect the subcellular localization of the NQO1 protein in A549 human lung cancer cells. The correlation between NQO1 expression and clinicopathological characteristics were evaluated by Chi-square test and Fisher's exact tests. The disease-free survival (DFS) and overall survival (OS) rates of NSCLC patients were calculated by the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. RESULTS: The NQO1 protein showed a mainly cytoplasmic staining pattern in lung cancer cells, including adenocarcinoma and squamous cell carcinoma (SCC). Both positive rate and strongly positive rate of NQO1 protein expression were significantly higher in NSCLC (59.3% and 28.0%) than that in adjacent non tumor (8.0% and 1.3%) and normal lung tissues (0%). The positive rate of NQO1 was related with clinical stage and lymph node metastasis, and the strongly positive rate of NQO1 protein was significantly correlated with tumor size, poor differentiation, advanced clinical stage and lymph node metastasis in NSCLC. Additionally, survival analyses showed that the patients with NQO1 positive expression had lower OS rates compared with those with NQO1 negative expression in the groups of T1-2, T3-4, without LN metastasis and stage I-II of NSCLC, respectively; however, in the groups of patients with LN metastasis or III-IV stages, OS rate was not correlated with NQO1 expression status. Moreover, multivariate analysis suggested that NQO1 emerged as a significant independent prognostic factor along with tumor size, differentiation, lymph node metastasis and clinical stage in patients with NSCLC. CONCLUSIONS: NQO1 is upregulated in NSCLC, and it may be a useful poor prognostic biomarker and a potential therapeutic target for patients with NSCLC.

[CK7, CK20, SOX10 and CDX2: expressions and diagnostic values in primary adenocarcinoma of the sinonasal tract].

OBJECTIVE: To explore the expressions of the cytokeratin 7 (CK7), cytokeratin 20 (CK20), SOX10 and cadual type homeobox transcription factor 2 (CDX2) in primary adenocarcinoma of the sinonasal tract, and evaluate their diagnostic values. METHODS: A total of 41 paraffin-embeded specimens of primary adenocarcinoma of the sinonasal tract treated in Beijing Tongren Hospital of Capital Medical University were selected from May 2002 to January 2015. All cases were confirmed by histology and clinical data, including 12 cases of non-intestinal sinonasal adenocarcinomas (non-ITACs), 10 cases of intestinal sinonasal adenocarcinomas (ITACs) and 19 cases of salivary gland-type adenocarcinomas (including 12 cases of adenoid cystic carcinomas, 3 cases of polymorphous low grade adenocarcinomas, 2 cases of mucinous adenocarcinomas and 2 cases of acinar cell carcinomas). Expressions of CK7, CK20, SOX10 and CDX2 were assessed by immunohistochemistry staining method. RESULTS: Nuclear staining for CDX2 was identified in all the ITACs,including diffuse nuclear staining in 8 cases and partial nuclear staining in 2 cases. Cytoplasmic staining for CK20 was identified in 9 cases of ITACs, and partial cytoplasmic staining was found in 1 case of non-ITACs, while CK20 was negative in all other adenocarcinomas.Seven cases of ITACs were negative for CK7, while CK7 was positive in all other adenocarcinomas. CK7, but not CDX2 and CK20, was expressed in normal sinonasal epithelium. SOX10 was negative in 10 cases of ITACs and 2 cases of non-ITACs, and positive in all other adenocarcinomas. The sensitivity of CK7-, CK20+, SOX10- and CDX2+ in primary ITACs of the sinonasal tract were 70.0%, 90.0%, 100%, 100%, respectively, and the specificity were 100%, 96.8%, 93.5%, 100%, respectively. CONCLUSIONS: Expressions of CK7-, CK20+, SOX10- and CDX2+ have high sensitivity and specificity in ITACs and can be used as a reliable diagnostic marker for primary intestinal-type adenocarcinoma of the sinonasal tract. Additionally, diagnostic value of CDX2 in primary intestinal-type adenocarcinoma of the sinonasal tract is superior to CK20, CK7 and SOX10.

Prognostic implications of ezrin and phosphorylated ezrin expression in non-small cell lung cancer.

BACKGROUND: The cytoskeletal organizer ezrin is a member of the ezrin-radixin-moesin (ERM) family and plays important roles in not only cell motility, cell adhesion, and apoptosis, but also in various cell signaling pathways. Phosphorylation at Thr-567 and Tyr-353 are key regulatory events in the transition of the dormant to active form of ezrin. This study investigated the prognostic implications of ezrin and phosphorylated ezrin (p-ezrin) expression in non-small cell lung carcinoma (NSCLC). METHODS: Ezrin and p-ezrin protein expressions were examined by immunohistochemistry in 150 NSCLC and adjacent non-tumor tissues and 14 normal lung tissues. qRT-PCR was used to determine ezrin mRNA expression levels in fresh tissues. The correlations between overexpression of ezrin and p-ezrin and the clinicopathological features of NSCLC were analyzed. The survival rates were calculated by the Kaplan-Meier method for 108 NSCLC cases. RESULTS: Ezrin and ezrinThr-567 proteins showed cytosolic and membranous staining patterns; however, ezrinTyr-353 protein only showed cytosolic staining. Ezrin and p-ezrin were significantly upregulated in NSCLC compared with the normal counterparts. Increased ezrin, ezrinThr-567, and ezrinTyr-353 levels were correlated with the late stage and poor differentiation of NSCLC. However, only ezrinThr-567 was correlated with the presence of lymph node metastasis. In regard to survival, only ezrinThr-567 was related with the overall survival time of patients with NSCLC, and both ezrin and ezrinThr-567 were associated with shortened survival time for patients with early stage NSCLC. CONCLUSIONS: Ezrin and p-ezrin, especially ezrinThr-567, may prove to be useful as a novel prognostic biomarker of NSCLC.

Meta-analysis of etrolizumab versus placebo in ulcerative colitis: safety and efficacy outcomes.

Background: The existing body of scientific literature offers inconclusive findings on the safety and therapeutic effectiveness of etrolizumab (ETR) for the treatment of ulcerative colitis (UC). Objectives: The goal of this meta-analysis is to furnish a comprehensive synthesis of evidence that evaluates the safety and therapeutic effects of ETR in the management of UC. Design: Meta-analysis. Data sources and methods: PubMed, Embase, and Web of science were searched to collect relevant English studies, and the reference lists of eligible studies were manually searched to avoid missing any eligible studies. Outcome measures encompassed clinical response, incidence of adverse events, histological remission, endoscopic remission, endoscopic improvement, and antidrug antibodies. Relevant data were extracted by two independent investigators. Results: The meta-analysis incorporated five eligible studies, involving a total of 1528 patients, with 1015 treated with ETR and 513 with placebo. The pooled analysis indicates that ETR is both effective and safe. The adverse event rates, endoscopic and histological response, as well as overall remission were comparable between the two groups. The monoclonal antibody group had a lower incidence rate of adverse reactions than the placebo group [odds ratio (OR): 0.81; 95% confidence interval (CI): 0.63-1.03; p = 0.09)]. Clinical response was higher in the ETR group than in the placebo group (OR: 1.56; 95% CI: 1.20-2.02; p = 0.0009), and endoscopic improvement was more favorable in the ETR group (OR: 1.88; 95% CI: 1.45-2,45; p < 0.00001). A higher rate of endoscopic remission was found in the ETR group than in the placebo group (OR: 2.48; 95% CI: 1.75-3.50; p < 0.00001); histological remission was significantly higher in the ETR group than in the placebo group (OR: 2.11; 95% CI: 1.55-2.86; p < 0.00001). The placebo group had a lower rate of positive antidrug antibodies (OR: 1.31; 95% CI: 0.79-2.17; p < 0.29), and the incidence of complications was significantly higher in the ETR group compared with the placebo group (OR: 2.05; 95% CI: 1.48-2.83; p < 0.0001). Conclusion: Given the heterogeneity and potential biases in the included studies, gastroenterologists should cautiously tailor drug delivery strategies based on their clinical experience and the unique needs of individual patients. PROSPERO registration: CRD42023396100.