Acute invasive fungal sinusitis with orbital tip syndrome in patients on long-term use of ruxolitinib: a case report.

INTRODUCTION: A long-term ruxolitinib-treated patient with primary myelofibrosis, who was co-infected with aspergillosis infection during a short period, developed acute invasive fungal sinusitis with consequent orbit apex syndrome. This may be the first reported case in the world. This is a 75-year-old Chinese man; the patient was admitted with 2-month history of headache accompanied by numbness and 8-day history of vision loss. The preliminary clinical diagnoses were suspected acute invasive fungal sinusitis or adenoid cystic carcinoma. We performed endoscopic debridement and antifungal therapy. About 90 days after surgery, magnetic resonance imaging revealed no recurrence of pathological tissue. CONCLUSION: One of the bases for the occurrence of invasive fungal sinusitis may be the patient's long-term use of ruxolitinib for essential thrombocythemia. Some patients with invasive fungal sinuses have atypical nasal symptoms and are referred to the corresponding departments with eye and headache as the first symptoms. It is suggested that enhanced magnetic resonance imaging should be performed at an early stage. Surgical treatment in combination with antifungal and enhanced immunotherapy can effectively prevent the spread of infection and reduce the risk of death.

Silencing of forkhead box C1 reduces nasal epithelial barrier damage in mice with allergic rhinitis via epigenetically upregulating secreted frizzled-related protein 5.

Allergic rhinitis (AR) is caused by immunoglobulin E (IgE)-mediated reactions to inhaled allergens, which leads to mucosal inflammation and barrier dysfunction. The transcription factor forkhead box C1 (FOXC1) has been identified to be associated with allergic inflammation. This study sought to uncover the role of FOXC1 in AR. A murine model of AR was induced by repeated intranasal ovalbumin (OVA) challenges. Results revealed that high FOXC1 expression was found in the nasal mucosal epithelium of AR mice. Nasal allergy symptoms, mucosal epithelial swelling, goblet cell hyperplasia and eosinophil infiltration in AR mice were attenuated after silencing of FOXC1. Knockdown of FOXC1 decreased the levels of T-helper 2 cytokines interleukin(IL)-4 and IL-13 in nasal lavage fluid, and serum OVA-specific IgE and histamine. Silencing of FOXC1 restored nasal epithelial integrity in AR mice by enhancing the expression of tight junctions (TJs) and adherence junction. Furthermore, knocking down FOXC1 increased tight junction expression and transepithelial electrical resistance (TEER) in IL-13-treated air-liquid interface (ALI) cultures of human nasal epithelial cells (HNEpCs). Mechanistically, silencing of FOXC1 induced DNA methylation of secreted frizzled-related protein 5 (SFRP5) promoter and increased its expression in the nasal mucosa of AR mice and IL-13-treated ALI cultures. FOXC1 overexpression transcriptionally activated DNA methyltransferase 3B (DNMT3B) in IL-13-treated ALI cultures. Knockdown of SFRP5 reversed the protection of FOXC1 silencing on epithelial barrier damage induced by IL-13. Collectively, silencing of FOXC1 reduced allergic inflammation and nasal epithelial barrier damage in AR mice via upregulating SFRP5, which may be attribute to DNMT3B-driven DNA methylation. Our study indicated that FOXC1 may represent a potential therapeutic target for AR.

Three Robust Isoreticular Metal-Organic Frameworks with High-Performance Selective CO2 Capture and Separation.

Based on the hard-soft acid base (HSAB) theory, three robust isoreticular metal-organic frameworks (MOFs) with nia topology were successfully synthesized by solvothermal reaction {[In3O(BHB)(H2O)3]NO3·3DMA (JLU-MOF110(In)), [Fe3O(BHB)(H2O)3]NO3 (JLU-MOF110(Fe)), and [Fe2NiO(BHB)(H2O)3] (JLU-MOF110(FeNi)) (DMA = N,N-dimethylacetamide, H6BHB = 4,4″-benzene-1,3,5-triyl-hexabenzoic acid)}. Both JLU-MOF110(In) and JLU-MOF110(Fe) are cationic frameworks, and their BET surface areas are 301 and 446 m2/g, respectively. By modification of the components of metal clusters, JLU-MOF110(FeNi) features a neutral framework, and the BET surface area is increased up to 808 m2/g. All three MOF materials exhibit high chemical and thermal stability. JLU-MOF110(In) remains stable for 24 h at pH values ranging from 1 to 11, while JLU-MOF110(Fe) and JLU-MOF110(FeNi) persist to be stable for 24 h at pH from 1 to 12. JLU-MOF110(In) exhibits thermal stability up to 350 °C, whereas JLU-MOF110(Fe) and JLU-MOF(FeNi) can be stable up to 300 °C. Thanks to the microporous cage-based structure and abundant open metal sites, JLU-MOF110(In), JLU-MOF110(Fe), and JLU-MOF110(FeNi) have excellent CO2 capture capacity (28.0, 51.5, and 99.6 cm3/g, respectively, under 298 K and 1 bar). Interestingly, the ideal adsorption solution theory results show that all three MOFs exhibit high separation selectivity toward CO2 over N2 (35.2, 43.2, and 43.2 for CO2/N2 = 0.15/0.85) and CO2 over CH4 (14.4, 11.5, and 10.1 for CO2/CH4 = 0.5/0.5) at 298 K and 1 bar. Thus, all three MOFs are potential candidates for CO2 capture and separation. Among them, JLU-MOF110(FeNi) displays the best separation potential, as revealed by dynamic column breakthrough experiments.

[Misdiagnosis of adenoid cystic carcinoma of oropharynx: a case report].

Adenoid cystic carcinoma usually occurs in the salivary glands of the head and neck. It is a malignant tumor with a high degree of malignancy, resistance to radiotherapy and chemotherapy and poor prognosis. The clinical course of adenoid cystic carcinoma is slow and easy to be misdiagnosed. The main diagnosis and treatment means are individualized and precise treatment under the multi-disciplinary consultation mode, that is, surgical treatment and radiotherapy and chemotherapy. Adenoid cystic carcinoma is prone to relapse and hematologic metastasis, and the traditional radiotherapy and chemotherapy based therapies have not achieved satisfactory efficacy in the past three decades. How to detect, diagnose and treat early is an urgent task faced by clinicians.

A cuproptosis-related lncRNA signature predicts the prognosis and immune cell status in head and neck squamous cell carcinoma.

Introduction: The incidence of head and neck squamous cell carcinoma (HNSCC), one of the most prevalent tumors, is increasing rapidly worldwide. Cuproptosis, as a new copper-dependent cell death form, was proposed recently. However, the prognosis value and immune effects of cuproptosis-related lncRNAs (CRLs) have not yet been elucidated in HNSCC. Methods: In the current study, the expression pattern, differential profile, clinical correlation, DNA methylation, functional enrichment, univariate prognosis factor, and the immune effects of CRLs were analyzed. A four-CRL signature was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm. Results: Results showed that 20 CRLs had significant effects on the stage progression of HNSCC. Sixteen CRLs were tightly correlated with the overall survival (OS) of HNSCC patients. Particularly, lnc-FGF3-4 as a single risk factor was upregulated in HNSCC tissues and negatively impacted the prognosis of HNSCC. DNA methylation probes of cg02278768 (MIR9-3HG), cg07312099 (ASAH1-AS1), and cg16867777 (TIAM1-AS1) were also correlated with the prognosis of HNSCC. The four-CRL signature that included MAP4K3-DT, lnc-TCEA3-1, MIR9-3HG, and CDKN2A-DT had a significantly negative effect on the activation of T cells follicular helper and OS probability of HNSCC. Functional analysis revealed that cell cycle, DNA replication, and p53 signal pathways were enriched. Discussion: A novel CRL-related signature has the potential of prognosis prediction in HNSCC. Targeting CRLs may be a promising therapeutic strategy for HNSCC.

Cortisol synergizing with endoplasmic reticulum stress induces regulatory T-cell dysfunction.

The dysfunction of regulatory T cell (Treg) is associated with the pathogenesis of many immune diseases. The regiments used to re-establish Treg's function are currently unsatisfactory and need to be improved. The purpose of this study is to elucidate the synergistic effects of cortisol and endoplasmic reticulum (ER) stress on impairing regulatory T cell functions. In this study, blood samples were collected from patients with food allergy (FA). Immune cells were purified from blood specimens by flow cytometry. A mouse model of FA was established with ovalbumin as a specific antigen. We observed that serum cortisol levels of FA patients were negatively correlated with peripheral Treg counts. Overwhelmed ER stress status was detected in Tregs of FA patients. The antigen-specific immune response induced ER stress in Tregs, which was exacerbated by concurrent cortisol exposure. ER stress mediated the effects of cortisol on impairing the immune suppressive ability of Tregs. The expression of Rnf20 was observed in Tregs upon exposure to cortisol. Rnf20 reduced the expression of Foxp3 and transforming growth factor (TGF)-ß in Tregs. Rnf20 inhibition re-established the immunosuppressive functions of Tregs obtained in patients with FA. The experimental FA in mice was attenuated by inhibition of Rnf20 in Tregs. In summary, specific immune response in synergy with cortisol to induce the expression of Rnf20 in Tregs. Rnf20 reduces the levels of Foxp3 and TGF-ß to impair the immune suppressive function. Inhibition of Rnf20 can restore the immune suppressive ability of Tregs obtained from FA patients.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Projection of Premature Cancer Mortality in Hunan, China, Through 2030: Modeling Study.

BACKGROUND: The United Nations Sustainable Development Goals for 2030 include reducing premature mortality from noncommunicable diseases by one-third. Although previous modeling studies have predicted premature mortality from noncommunicable diseases, the predictions for cancer and its subcategories are less well understood in China. OBJECTIVE: The aim of this study was to project premature cancer mortality of 10 leading cancers in Hunan Province, China, based on various scenarios of risk factor control so as to establish the priority for future interventions. METHODS: We used data collected between 2009 and 2017 from the Hunan cancer registry annual report as empirical data for projections. The population-attributable fraction was used to disaggregate cancer deaths into parts attributable and unattributable to 10 risk factors: smoking, alcohol use, high BMI, diabetes, physical inactivity, low vegetable and fruit intake, high red meat intake, high salt intake, and high ambient fine particulate matter (PM2.5) levels. The unattributable deaths and the risk factors in the baseline scenario were projected using the proportional change model, assuming constant annual change rates through 2030. The comparative risk assessment theory was used in simulated scenarios to reflect how premature mortality would be affected if the targets for risk factor control were achieved by 2030. RESULTS: The cancer burden in Hunan significantly increased during 2009-2017. If current trends for each risk factor continued to 2030, the total premature deaths from cancers in 2030 would increase to 97,787 in Hunan Province, and the premature mortality (9.74%) would be 44.47% higher than that in 2013 (6.74%). In the combined scenario where all risk factor control targets were achieved, 14.41% of premature cancer mortality among those aged 30-70 years would be avoided compared with the business-as-usual scenario in 2030. Reductions in the prevalence of diabetes, high BMI, ambient PM2.5 levels, and insufficient fruit intake played relatively important roles in decreasing cancer premature mortality. However, the one-third reduction goal would not be achieved for most cancers except gastric cancer. CONCLUSIONS: Existing targets on cancer-related risk factors may have important roles in cancer prevention and control. However, they are not sufficient to achieve the one-third reduction goal in premature cancer mortality in Hunan Province. More aggressive risk control targets should be adopted based on local conditions.

One-off low-dose CT screening of positive nodules in lung cancer: A prospective community-based cohort study.

BACKGROUND: To improve the early stage diagnosis and reduce the lung cancer (LC) mortality for positive nodule (PN) population, data on effectiveness of PN detection using one-off low-dose spiral computed tomography (LDCT) screening are needed to improve the PN management protocol. We evaluate the effectiveness of PN detection and developed a nomogram to predict LC risk for PNs. METHODS: A prospective, community-based cohort study was conducted. We recruited 292,531 eligible candidates during 2012-2018. Individuals at high risk of LC based on risk assessment underwent LDCT screening and were divided into PN and non-PN groups. The effectiveness of PN detection was evaluated in LC incidence, mortality, and all-cause mortality. We performed subgroup analysis of characteristic variables for the association between PN and LC risk. A competing risk model was used to develop the nomogram. RESULTS: Participants (n = 14901) underwent LDCT screening; PNs were detected in 1193 cases (8·0%). After a median follow-up of 6·1 years, 193 were diagnosed with LC (1·3%). Of these, 94 were in the PN group (8·0%). LC incidence, mortality, and all-cause mortality were significantly higher in the PN group (adjusted hazard ratios: 10.60 (7.91-14.20), 7.97 (5.20-12.20), and 1.94 (1.51-2.50), respectively). Additionally, various PN characteristics were associated with an increased probability of developing LC. The C-index value of the nomogram for predicting LC risk of PN individuals was 0·847. CONCLUSIONS: The protocol of PNs management for improvement could focus on specific characteristic population and high-risk PN individuals by nomogram assessment.

Development and validation of tumor-size-stratified prognostic nomograms for patients with uterine sarcoma: A SEER database analysis.

BACKGROUND: Tumor-size-stratified analysis on the prognosis of uterine sarcoma is insufficient. This study aimed to establish the tumor-size-stratified nomograms to predict the 3- and 5-year overall survival (OS) of patients with uterine sarcoma. METHODS: The data analyzed in this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. We collected data from patients with uterine sarcoma diagnosed between 2004 and 2015. According to the median tumor size of 7.8 cm, the enrolled patients were divided into two tumor size (TS) groups: TS <7.8 cm and TS ≥7.8 cm. Patients in each group were randomly divided into the training and validation cohorts with a ratio of 7:3. Chi-square test was used to compare differences between categorical variables. Multivariate Cox regression models were used to identify significant predictors. We calculated the concordance index (C-index) and the area under the receiver operating characteristics curve (AUC) to validate the nomograms. RESULTS: Compared with TS <7.8 cm group, TS ≥7.8 cm group had more patients of 45-64 years group, higher black race prevalence, higher proportion of myometrium tumor, higher stage, and higher grade; In the TS <7.8 cm training cohort, six variables (age, race, marital status, tumor primary site, stage, and grade) were identified as significantly associated with OS in multivariate analysis. However in the TS ≥7.8 cm training cohort, only four variables (surgery on primary site, tumor size, stage, and grade) were significantly identified; The C-index of two nomograms were 0.80 and 0.73 in training cohorts, respectively, and the AUC values for 3- and 5-year OS predictions in training cohorts were all above 0.80. Similar results were observed in validation cohorts. CONCLUSIONS: This study found that the significant prognostic factors were different between two tumor size groups of uterine sarcoma patients. The tumor-size-stratified nomograms, which we constructed and validated, might be useful to predict the probability of survival for patients with uterine sarcoma.

Acceptability of Pre-Exposure Prophylaxis and Non-Occupational Post-Exposure Prophylaxis among Men Who Have Sex with Men in Guilin, China.

Pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (nPEP) are both effective strategies for preventing HIV. There is limited information about the acceptability of these prevention measures in undeveloped areas of China. We aimed to examine the acceptability of PrEP and nPEP and their determinants among men who have sex with men (MSM). 219 MSM were recruited in Guilin, China. In total, 28.6% (95% CI: 20.0-41.0) and 35.9% (95% CI: 27.3-49.5) of the participants had heard of PrEP and nPEP, respectively, while 57.0% (95% CI: 43.1-68.2) and 58.6 (95% CI:44.8-68.8) reported they would be willing to use PrEP and nPEP after the methods were explained. A higher acceptability of PrEP was seen among participants who were previously married (aOR = 3.30; 95% CI: 1.22-9.19), working as a laborer (aOR = 5.13; 95% CI: 1.64-17.59), migrant workers/farmers (aOR = 2.56; 95% CI: 1.15-5.79), government employees (aOR = 4.76; 95%CI: 1.80-13.02), had higher social support (aOR = 1.05; 95% CI: 1.03-1.08), and had been previously tested for HIV (aOR = 2.79; 95% CI: 1.36-5.94). A higher acceptability of nPEP was associated with those having higher social support (aOR = 1.06; 95% CI: 1.04-1.09), not knowing their sexual partner's HIV status (aOR = 2.72; 95% CI: 1.23-6.12), and having a prior HIV test (aOR = 5.53; 95% CI: 2.58-12.51). PrEP and nPEP are acceptable, especially among MSM with higher social support and had received a previous HIV test. Effective education and different dissemination strategies to promote the acceptance of PrEP and nPEP among MSM are needed.

[Analysis of clinical effect of nasal endoscope-assisted nasal columella approach for simultaneous correction of nasal septum deviation and crooked nose deformity].

Objective:To analyze the clinical effect of nasal endoscope-assisted nasal columella approach in the correction of nasal septum deviation and crooked nose deformity. Methods:The clinical data of 33 patients with deviation of nasal septum with crooked nose deformity in First Affiliate Hospital of Air Force Military Medical University from January 2016 to June 2019 were collected. All patients underwent surgery under general anesthesia. Nasal columella inverted "V" incision was used to expose and release. The deviated nasal septum cartilage and bone were removed with the assistance of nasal endoscope. Twelve（36.4%） patients underwent osteotomy of nasal bone and frontal process of maxilla at the same time, 13（39.4%） patients used autologous nasal septum to reshape the tip, back and external nose. Results:During a follow-up of 18 months to 60 months, 30（90.9%） patients were satisfied with the improvement of postoperative nasal function, 3（9.1%） patients were basically satisfied; 23（69.7%） patients were satisfied with the appearance of the nose after operation, 8（24.2%） patients were basically satisfied, and 2（6.1%） patients were dissatisfied. No postoperative complications such as nasal adhesion, nasal septum perforation, nasal septum hematoma and nasal dorsal collapse occurred in all patients. Conclusion:The nasal endoscope-assisted nasal columella approach and the correction of nasal septum deviation and crooked nose deformity can solve the nasal deformity and nasal ventilation function at the same time, realize the unity of cosmetology and function, and reduce the frequency and cost of surgical treatment at the same time. The effect is good, and the patients benefit greatly.

Nrg1/ErbB2 regulates differentiation and apoptosis of neural stem cells in the cochlear nucleus through PI3K/Akt pathway.

Sensorineural hearing loss (SNHL) is a common causes of disability. Neural stem cells (NSCs) from the cochlear nuclei have been considered to be a potential direction for the treatment of SNHL. Neuregulin 1 (NRG1)/ErbB2 signaling displays an essential role in nervous system development. In this study, we aimed to explore the roles of NRG1/ErbB2 in differentiation and apoptosis of cochlear nuclei NSCs. The data showed that the expression of NGR1 and ErbB2 in cochlear nuclei NSCs isolated from rats were increased with the age of rats. NRG1 treatment reduced the nestin-positive cells number, increased the MAP2-positive and GFAP-positive cells number, decreased the expression of cleaved-caspase-3, and increased the activation of PI3K/AKT. ErbB2 knockdown by lentiviral-mediated ErbB2 shRNA infection reversed the effect of NRG1 on cochlear nuclei NSCs. LY294002 administration further enhanced the effect of ErbB2 silencing on the expression of nestin, MAP2, GFAP and cleaved-caspase-3. Taken together, NRG1/ErbB2 regulates differentiation and apoptosis of cochlear nucleus NSCs through PI3K/Akt pathway.

The regulatory role of SFRP5/WNT5A axis in allergic rhinitis through inhibiting JNK pathway activation and lowering mucin generation in human nasal epithelial cells.

Allergic rhinitis (AR) is tightly associated with type 2 inflammation. SFRP5 combined with WNT5A mainly inhibits chronic inflammatory response, atherosclerosis, and other metabolic disorders. However, the effect of SFRP5/WNT5A axis on recombinant human interleukin-13 (rhIL-13)-induced inflammation has not been studied. In this study, we aimed to investigate whether secreted frizzled-related protein 5 (SFRP5) could modulate the production of cytokines relevant to eosinophil infiltration and mucin secretion through blocking the activation of Wnt family 5A (WNT5A) signaling pathway. A mouse model of AR demonstrated low expression of SFRP5 and high expression of WNT5A, and indicated that the number of eosinophil and goblet cells was increased, concomitant with elevated IL-13, colony stimulating factor 2 (CSF2), chemokine ligand 11 (CCL11), Mucin 4, and Mucin 5AC levels. Furthermore, lentivirus-SFRP5 overexpression up-regulated the expression of SFRP5 but down-regulated WNT5A level, and inhibited the activation of JNK pathway via decreasing p-JNK1/2 (Thr183/Tyr185) and p-c-Jun (Ser73) protein expressions in rhIL-13-treated human nasal epithelial cells (HNEpCs). Noticeably, SFRP5 overexpression markedly reduced rhIL-13-induced inflammatory protein and mucin generation through lowered CSF2, CCL11, Mucin 4, as well as Mucin 5AC levels. Taken together, these findings confirmed the regulatory role of SFRP5/WNT5A axis in rhIL-13-mediated inflammatory response in HNEpCs.

Prognostic and clinicopathological value of Ki-67 expression in patients with nasopharyngeal carcinoma: a meta-analysis.

BACKGROUND: This meta-analysis aimed to identify the prognostic role of Ki-67 in patients with nasopharyngeal carcinoma (NPC). METHODS: Relevant studies were retrieved in the PubMed, Embase, Web of Science, and Cochrane Library databases up to November 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the association between Ki-67 expression and survival outcomes. Combined odds ratios (ORs) and 95% CIs were measured as effect size on the association between Ki-67 expression and clinical factors. RESULTS: A total of eight studies involving 936 patients with NPC were included in this meta-analysis. The pooled HR indicated that Ki-67 expression was significantly associated with poor overall survival (HR = 2.86, 95% CI = 1.91-4.27, p < 0.001), progression-free survival (HR = 1.78, 95% CI = 1.15-2.74, p = 0.009), and distant metastasis-free survival (HR = 1.65, 95% CI = 1.15-2.36, p = 0.007). However, there was no significant correlation between Ki-67 expression and local recurrence-free survival (HR = 1.07, 95% CI = 0.54-2.14, p = 0.843). Ki-67 overexpression was associated with higher T stage (OR = 1.48, 95% CI = 1.00-2.20, p = 0.052), and the relationship between Ki-67 expression and advanced stage was nearly significant (OR = 2.25, 95% CI = 0.99-5.14, p = 0.054). However, high Ki-67 expression was not significantly correlated with sex, age, N stage, or histological type. CONCLUSION: This meta-analysis demonstrated that Ki-67 overexpression was a significant marker for poor prognosis in patients with NPC. Ki-67 should be recommended as a useful index for prognostication in patients with NPC.

Chlorogenic acid ameliorated allergic rhinitis-related symptoms in mice by regulating Th17 cells.

Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of nasal mucosa provoking T helper cell (Th) 17 response. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in various agricultural products, possesses antiviral, anti-inflammatory, and antibacterial properties. However, the effect of CGA on AR is unclear. Thus, our study explored the effect of CGA in modulating AR-related symptoms and immunoreaction, especially Th17 response. AR mice were induced by ovalbumin (OVA) administration and further treated with CGA or dexamethasone (Dex). The frequencies of rubbing and sneezing of AR mice were recorded. Histopathological analysis of nasal mucosa was conducted by Hematoxylin-Eosin and Periodic acid-Schiff stainings. The serum and nasal mucosa levels of OVA-immunoglobulin (Ig)E, interferon (IFN)-γ, retinoic acid-associated nuclear orphan receptor (ROR)-γt, and interleukin (IL)-17A were measured by enzyme-linked immunosorbent assay, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), or Western blot. The ratio of CD4+IL-17+Th17 cells to CD4+ T cells in peripheral blood of AR mice was assessed by flow cytometer. CGA diminished the frequencies of rubbing and sneezing of AR mice in a concentration-dependent manner. CGA attenuated histopathological abnormalities and decreased goblet cell number in nasal mucosa of AR mice. CGA decreased the serum levels of OVA-IgE, ROR-γt, and IL-17A, while increasing the serum level of IFN-γ in AR mice. Meanwhile, CGA decreased the ratio of CD4+IL-17+Th17 cells to CD4+T cells in peripheral blood and the mRNA and protein levels of IL-17A and ROR-γt in AR mice. CGA ameliorated AR-related symptoms in mice by regulating Th17 cells, which could be a candidate for the treatment of AR.

Development and external validation of a nomogram to predict the risk of Upper gastrointestinal precancerous lesions in a non-high-incidence area.

BACKGROUND: Upper gastrointestinal precancerous lesions (UGPL) is the major preventable disease in non-high-incidence area. A prognostic nomogram was constructed to predict and identity susceptible population of UGPL before endoscope screening. METHODS: We recruited 300 ,016 eligible participants for upper gastrointestinal cancer (UGC) screening aged 40-74 years from two cities in Hunan province from 2012 to 2019. Individuals at high risk of UGC on basis of questionnaire estimation underwent endoscopic screening. Participants in two cities accepting endoscopy were used as training and external validation cohorts, respectively. A nomogram was developed based on independent prognostic factors of UGPL determined in multivariable logistic regression analysis. RESULTS: Of 35, 621 with high risk for UGC, 10, 364 subjects undertook endoscopy (participation rate of 29.1%). The detection rate for UGPL was 4.55%. The nomogram showed that age, gender, mental trama, picked food, and atrophic gastritis history in a descending order were significant contributors to UGPL risk. The C-index value of internal and external validation of the model is 0.612 and 0.670, respectively. The calibration data for UGPL showed optimal agreement between the nomogram prediction and actual observation. Furthermore, high-risk and low-risk group divided based on score from the nomogram predicted a significantly distinct detection rate. CONCLUSION: The nomogram provides screening workers a simple and accurate tool for identifying individuals at a higher risk of UGPL as primary screening before endoscopy among Chinese population in non-high-risk areas, thus reducing the incidence of UGC by improving the UGPL detection.

[Osteoradionecrosis of skull base: clinical analysis and experience].

Objective:To discuss the diagnosis and treatment process of skull base osteoradionecrosis and improve the recognization of this disease. Method:We reviewd skull base and nasopharyngeal osteoradionecrosis in 7 patients retrospectively, including 5 nasopharyngeal carcinoma, 1 squamous cell carcinoma of sphenoid sinus, 1 adenoid cystic carcinoma; 6 patientd received skull base debridement surgery and the other one attempted but failed because of her unstable condition. Result:Follow-up period ranged from 3 to 31 months （mean 11.5 month）. During the review time, 2 patients died, 1 patient still had osteoradionecrosis with partly alleviated clinical symptom. At the latest follow-up visit, she was diagnosed as tumor recurrence and was advised to take targeted therapy by multi-discipline team; the symptom was significant improved in the rest of the patients. Conclusion:Osteoradionecrosis of skull base is often associated with other post-radiotherapy related complications. Once diagnosed definitely, extensive skull base debridement surgery should be performed in early time, which can significantly relieve symptoms, improve living quality and reduce the incidence of lethal complications.

Integrative analysis of miRNAs-mRNAs reveals that miR-182 up-regulation contributes to proliferation and invasion of nasopharyngeal carcinoma by targeting PTEN.

OBJECTIVE: Several miRNAs have been found to be abnormally expressed during nasopharyngeal carcinoma development. Nevertheless, the interaction between miRNAs and downstream genes remains unexploited. In this study, we aim to investigate miRNAs-mRNAs interaction and the mechanism of miR-182 in NPC. RESULTS: Integrative analysis identified several hub-miRNAs that drive NPC pathogenesis. The expression of miR-182 was notably increased in 32 NPC tissues and cell lines (CNE1 and 5-8F). Up-regulation of miR-182 was strongly correlated with poor prognosis of NPC patients. Moreover, the proliferation and invasion of NPC cells were notably increased in miR-182 mimics condition and decreased in miR-182 inhibitor condition. Furthermore, PTEN was verified to be a target of miR-182 and overexpression of PTEN could abrogate the promotion effect of miR-182 mimics on NPC invasion. CONCLUSIONS: We identified several hub-miRNAs that may drive NPC pathogenesis. MiR-182 could promote proliferation and invasion of NPC cells via targeting PTEN, which provides a new insight into the clinical therapy of NPC. MATERIALS AND METHODS: Genome-wide miRNAs of NPC tissues was analyzed using high-throughput sequencing and bioinformatics tools. QRT-PCR experiment was conducted to measure relative expression level. Dual-luciferase reporter assay was used to verify target relationship. The proliferation and invasion of transfected cells were measured by CCK-8 and transwell assay.

Community-Based Upper Gastrointestinal Cancer Screening in a Randomized Controlled Trial: Baseline Results in a Non-high-incidence Area.

A cluster-randomized controlled trial (RCT) was conducted to evaluate to the effectiveness of reducing mortality of upper gastrointestinal cancer (UGC) and feasibility of screening through a questionnaire combined with endoscopy in non-high-incidence urban areas in China. The trial design, recruitment performance, and preliminary results from baseline endoscopy are reported. Seventy-five communities in two urban cities with a non-high-incidence of UGC were randomized to a screening endoscopy arm (n = 38) or a control arm (n = 37). In the screening arm, individuals at high risk of UGC underwent endoscopic screening. The primary outcome was the UGC mortality, and secondary outcomes included the UGC detection rate, incidence rate, survival rate, and clinical stage at the time of diagnosis. A total of 10,416 and 9,565 individuals were recruited into the screening and control arms, respectively. The participation rate was 74.3%. In the screening arm, 5,242 individuals (50.3%) were estimated to be high-risk. Among them, 2,388 (45.6%) underwent endoscopic screening. Age and household income were associated with undergoing endoscopy. Three early esophageal cancer (0.13%), one gastric cancer (0.04%), 29 precancerous esophageal lesions (1.21%), and 53 precancerous gastric lesions (2.22%) were detected. Age, sex, a family history of cancer, intake of meat-egg-milk frequently, superficial gastritis, and clinical symptoms of gastric cancer were associated with the presence of precancerous lesions. The detection rate was low using endoscopic screening in non-high-incidence area given the relatively low compliance rate. These findings provide a reference for designing effective community-based UGC screening strategies in non-high-incidence urban areas.