Topical Adenosine Inhibits Inflammation and Mucus Production in Viral Acute Rhinosinusitis.

OBJECTIVE: Viral acute rhinosinusitis (ARS) is the leading cause of work and school absence and antibiotic over-prescription. There are limited treatment options available to ameliorate the symptoms caused by viral ARS. We have previously demonstrated that topical adenosine treatment enhances mucociliary clearance in the sino-nasal tract. Here, we assessed the therapeutic potential of topical adenosine in a mouse model of viral ARS. METHODS: The effect of topical adenosine on inflammatory response and mucin gene expression was examined in a mouse model of viral ARS induced by respiratory syncytial virus (RSV) nasal-only infection. We also investigated the inflammatory effect of both endogenous and exogenous adenosine in the sino-nasal tract. RESULTS: Topical adenosine significantly inhibited the expression of pro-inflammatory cytokines, goblet hyperplasia, mucin expression, and cell damage in the nose of mice with viral ARS. This treatment did not prolong virus clearance. This inhibitory effect was primarily mediated by the A2A adenosine receptor (AR). Although previous studies have shown that adenosine induces a robust inflammatory response in the lungs, neither endogenous nor exogenous adenosine produced inflammation in the sino-nasal tract. Instead, exogenous adenosine inhibited the baseline expression of TNF and IL-1ß in the nose. Additionally, baseline expression of ARs was lower in the nose than that in the trachea and lungs. CONCLUSION: We demonstrated that intranasal adenosine administration effectively decreased inflammation and mucus production in a mouse model of viral ARS. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:2095-2103, 2023.

A Steadier Hand: The First Human Clinical Trial of a Single-Use Robotic-Assisted Surgical Device for Cochlear Implant Electrode Array Insertion.

OBJECTIVE: To evaluate the safety and utility of an investigational robotic-assisted cochlear implant insertion system. STUDY DESIGN: Prospective, single-arm, open-label study under abbreviated Investigational Device Exemption requirements. SETTING: All procedures were performed, and all data were collected, at a single tertiary referral center. PATIENTS: Twenty-one postlingually deafened adult subjects that met Food and Drug Administration indication criteria for cochlear implantation. INTERVENTION: All patients underwent standard-of-care surgery for unilateral cochlear implantation with the addition of a single-use robotic-assisted insertion device during cochlear electrode insertion. MAIN OUTCOME MEASURES: Successful insertion of cochlear implant electrode array, electrode array insertion time, postoperative implant function. RESULTS: Successful robotic-assisted insertion of lateral wall cochlear implant electrode arrays was achieved in 20 (95.2%) of 21 patients. One insertion was unable to be achieved by either robotic-assisted or manual insertion methods, and the patient was retrospectively found to have a preexisting cochlear fracture. Mean intracochlear electrode array insertion time was 3 minutes 15 seconds. All implants with successful robotic-assisted electrode array insertion (n = 20) had normal impedance and neural response telemetry measures for up to 6 months after surgery. CONCLUSIONS: Here we report the first human trial of a single-use robotic-assisted surgical device for cochlear implant electrode array insertion. This device successfully and safely inserted lateral wall cochlear implant electrode arrays from the three device manufacturers with devices approved but he Food and Drug Administration.

Identification of an ATP/P2X7/mast cell pathway mediating ozone-induced bronchial hyperresponsiveness.

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast cells restored ozone-induced BHR. Despite equal numbers of mast cells in reconstituted mouse lungs, mice reconstituted with P2X7-/- mast cells demonstrated significantly less robust BHR than mice reconstituted with WT mast cells. These results support a model where P2X7 on mast cells and other cell types contribute to ozone-induced BHR.

Targeting USP22 with miR­30­5p to inhibit the hypoxia­induced expression of PD­L1 in lung adenocarcinoma cells.

Lung cancer is one of the most common forms of cancer and accounts for a significant proportion of all cancer­related deaths. Lung adenocarcinoma (LUAD) accounts for approximately 40% of all cases of lung cancer. In recent years, new developments in both the diagnosis and treatment of LUAD have been achieved. Unfortunately, the prognosis remains poor for patients with malignant LUAD. Hypoxia is a common characteristic of solid tumors and induce the immune evasion by increasing the expression of programmed cell death­ligand­1 (PD­L1) in the tumor. In this study, it was predicted that ubiquitin­specific peptidase 22 (USP22) is the direct target of the microRNA (miR)­30­5p family, including miR­30a­5p, miR­30b­5p, miR­30c­5p, miR­30d­5p and miR­30e­5p. Furthermore, the binding of USP22 with the miR­30­5p family was confirmed by luciferase assay. In addition, it was demonstrated that targeting USP22 via the miR­30­5p family inhibited the induction of PD­L1 expression in hypoxic conditions, thus preventing activated T cells from killing LUAD cells. Our results indicated that miR­30a­5p, miR­30b­5p, miR­30c­5p, miR­30d­5p and miR­30e­5p represent new targets for the treatment of LUAD.

High expression of CIN85 promotes proliferation and invasion of human esophageal squamous cell carcinoma.

SH3 domain­containing kinase­binding protein 1 (CIN85), an 85 kDa protein known to be a member of the signal adaptor family, is abnormally expressed in several human malignancies and has been found to be involved in the growth, migration and invasion of these tumors. The objective of the present study was to clarify the clinical significance of CIN85 in human esophageal squamous cell carcinoma (ESCC), as well as its in vitro functions. CIN85 expression was evaluated in 129 cases of ESCC and its adjacent normal tissues using immunohistochemistry to explore its clinical relevance and prognostic value. The functions of CIN85 in the ESCC TE1 cell line were analyzed in vitro using the interfering short hairpin RNA silencing technique. MTS, wound healing, clone formation and Transwell assays were used to detect the proliferation, migration and invasion of ESCC cells. CIN85 expression was identified mainly in ESCCs and their adjacent normal tissues, and the high expression of CIN85 was significantly associated with advanced Tumor Node Metastasis stage and lymph node metastasis. CIN85 gene silencing significantly inhibited TE1 cell proliferation, migration and invasion. These results demonstrated that CIN85 was highly expressed in advanced stage ESCC and lymph node metastasis, and played a critical role in tumor proliferation and progression. Therefore, CIN85 may be a promising therapeutic target for human ESCC.

General Complications after Endoscopic Sinus Surgery in Smokers: A 2005-2016 NSQIP Analysis.

BACKGROUND: Exposure to cigarette smoke has been associated with a higher incidence of postoperative complications across a variety of surgical specialties. However, it is unclear if smoking increases this risk after endoscopic sinus surgery (ESS). Because complication rates after ESS are relatively low, a large national database allows for a statistically meaningful study of this topic. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) dataset from 2005 to 2016 was analyzed. Patients who underwent ESS were identified. Thirty-day postoperative complication rates between smokers and nonsmokers were compared. Complications included infection, thromboembolic events, reintubation, readmission, acute renal failure, and cardiovascular events. RESULTS: 921 patients who underwent ESS were identified. 182 (20%) were smokers and 739 (80%) were nonsmokers. 609 patients underwent outpatient ESS, while 312 patients underwent inpatient ESS. A total of 12 patients experienced postoperative surgical site infections involving the deeper tissues beyond the wound (organ/space SSI). On univariate analysis, smoking was associated with a higher incidence of organ/space SSI (P = .0067) and pulmonary embolism (P = .0321) after ESS. On multivariate logistic regression, smoking was associated with increased odds (4.495, 1.11- 8.17, P = .0347) of organ/space SSI after ESS. CONCLUSIONS: This study demonstrates an association between exposure to cigarette smoke and potentially serious surgical site infections in the 30-day postoperative period after ESS. Our findings may help when counseling smokers who are considering ESS. Further study is required to understand the nature of these infections and ways to prevent them.Level of Evidence: 2c ("health outcomes").

Meta-Analysis of Two Different Methods for Cervical Esophagogastric Anastomosis: Triangulating Versus Circular Stapling.

Background: The standard treatment for esophageal carcinoma is extensive resection of the tumor and esophagogastric anastomosis despite the high incidence of related anastomotic complications, such as stricture and leakage. Thus, the choice of the cervical esophagogastric anastomotic method-triangulating stapling (TS) versus circular stapling (CS)-is a critical decision for the surgeon. Aim: To compare the incidence of major adverse outcomes between TS and CS in patients with resectable thoracic esophageal cancer. Methods: For this meta-analysis, PubMed, Embase, Wiley Online Library, Google Scholar, Wanfang, and China National Knowledge Infrastructure databases were searched for subject-relevant studies by using a rigorous study protocol established according to the recommendations of the Cochrane Handbook. Anastomotic leakage, anastomotic stricture, and postoperative pulmonary complications were the primary endpoints used for comparison. Relative risk (RR) with 95% confidence intervals (CI) were calculated to assess the strength of association. Results: Six studies were selected by our inclusion/exclusion criteria and represented a total of 739 patients in our meta-analysis of TS (n = 376) versus CS (n = 363). The TS group showed a lower incidence of anastomotic stricture (RR: 0.23 [95% CI: 0.08-0.63]; P = .004) and pulmonary complications (RR: 0.57 [95% CI: 0.37-0.87]; P = .01). However, the incidence of anastomotic leakage was similar for the two groups (RR: 0.66 [95% CI: 0.41-1.09]; P = .1). Subgroup analysis of four studies in which the surgical methods were minimally invasive demonstrated the TS group to have a lower incidence of lung complications (RR: 0.55 [95% CI: 0.35-0.87]; P = .01), anastomotic leakage (RR: 0.36 [95% CI: 0.18-0.74]; P = .005), and anastomotic stricture (RR: 0.23 [95% CI: 0.05-0.98]; P = .05). Conclusion: The TS method for cervical esophagogastric anastomosis after esophagectomy had a lower incidence of anastomotic stricture and postoperative lung complications.

Nasal priming by a murine coronavirus provides protective immunity against lethal heterologous virus pneumonia.

The nasal mucosa is an important component of mucosal immunity. Immunogenic particles in inspired air are known to activate the local nasal mucosal immune system and can lead to sinonasal inflammation; however, little is known about the effect of this activation on the lung immune environment. Here, we showed that nasal inoculation of murine coronavirus (CoV) in the absence of direct lung infection primes the lung immune environment by recruiting activated monocytes (Ly6C+ inflammatory monocytes) and NK cells into the lungs. Unlike infiltration of these cells into directly infected lungs, a process that requires type I IFN signaling, nasally induced infiltration of Ly6C+ inflammatory monocytes into the lungs is IFN-I independent. These activated macrophages ingested antigen and migrated to pulmonary lymph nodes, and enhanced both innate and adaptive immunity after heterologous virus infection. Clinically, such nasal-only inoculation of MHV-1 failed to cause pneumonia but significantly reduced mortality and morbidity of lethal pneumonia caused by severe acute respiratory syndrome CoV (SARS-CoV) or influenza A virus. Together, the data indicate that the nose and upper airway remotely prime the lung immunity to protect the lungs from direct viral infections.

Successful Prediction of a Left Nonrecurrent Laryngeal Nerve in a Patient With Right-Sided Aorta and Aberrant Left Subclavian Artery.

BACKGROUND: Left nonrecurrent laryngeal nerve (LNRLN) is an extremely rare anatomic variant. The development of such anatomic variation requires the regression of both the fourth (aortic arch) and sixth (ductus arteriosus, DA) arches on the left side. Preoperative prediction of this variant is difficult but might reduce risk of nerve injury. METHODS: A 34-year-old female was indicated for thyroidectomy for a 2.4 cm follicular neoplasm and Graves' disease. Due to a positive medical history of 22q11.2 microdeletion and unexplained left vocal cord paralysis, a preoperative chest computed tomography (CT) scan was obtained and revealed a right-sided aorta (RSA) and aberrant left subclavian artery (ALSA) without Kommerell's diverticulum. A left-sided NRLN was then highly suspected. RESULTS: Thyroidectomy was performed under general anesthesia with the utilization of intraoperative laryngeal nerve monitoring. A LNRLN was confirmed intraoperatively. CONCLUSIONS: Right-sided aorta and ALSA indicate embryologic regression of the left fourth primitive aortic arch. The absence of Kommerell's diverticulum at the origin of the ALSA indicates the lack of high-pressure blood flow from the pulmonary artery to the ALSA through the ductus arteriosus during embryogenesis, suggesting the embryologic regression of the left sixth primitive aortic arch. The presence of all 3 radiologic features thus highly suggests the possibility of a LNRLN.

Mast Cell Deficiency Limits the Development of Chronic Rhinosinusitis in Mice.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common chronic diseases in adults in both developing and developed countries. The etiology and pathogenesis of CRS remain poorly understood, and the disease is refractory to therapy in many patients. Mast cell activation has been demonstrated in the sinonasal mucosa of patients with CRS; however, the specific contribution of mast cells to the development and pathogenesis of this disease has not been established. OBJECTIVE: The objective of this study was to investigate the role of mast cells in the development of CRS. METHODS: C57BL/6 wild-type and C57BL/6-Kit(W-sh/W-sh) mast cell-deficient mice were immunized by intraperitoneal allergen injection and subsequent chronic low dose intranasal allergen challenges. The sinonasal phenotypes of these groups were then evaluated and compared to saline-treated controls using radiologic, histologic, and immunologic methods. RESULTS: Wild-type mice exposed to chronic intranasal allergen developed many features seen in human CRS, including mucosal thickening, cystic changes, polyp development, eosinophilia, goblet cell hyperplasia, and mast cell activation. In contrast, sinonasal pathology was significantly attenuated in mast cell-deficient mice subjected to the same chronic allergen protocol. Specifically, tissue eosinophilia and goblet cell hyperplasia were reduced by approximately 50% compared to wild-type levels. Surprisingly, none of the mast cell-deficient mice subjected to chronic allergen challenge developed cystic changes or polypoid changes in the nose or sinuses. CONCLUSIONS: These data identify a critical role for mast cells in the development of many features of a mouse model of eosinophilic CRS, suggesting that therapeutic strategies targeting mast cells be examined in humans afflicted with this disease.

Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection.

Oxidative stress and chronic low-grade inflammation in the lungs are associated with aging and may contribute to age-related immune dysfunction. To maintain lung homeostasis, chronic inflammation is countered by enhanced expression of proresolving/antiinflammatory factors. Here, we show that age-dependent increases of one such factor in the lungs, a phospholipase A2 (PLA2) group IID (PLA2G2D) with antiinflammatory properties, contributed to worse outcomes in mice infected with severe acute respiratory syndrome-coronavirus (SARS-CoV). Strikingly, infection of mice lacking PLA2G2D expression (Pla2g2d(-/-) mice) converted a uniformly lethal infection to a nonlethal one (>80% survival), subsequent to development of enhanced respiratory DC migration to the draining lymph nodes, augmented antivirus T cell responses, and diminished lung damage. We also observed similar effects in influenza A virus-infected middle-aged Pla2g2d(-/-) mice. Furthermore, oxidative stress, probably via lipid peroxidation, was found to induce PLA2G2D expression in mice and in human monocyte-derived macrophages. Thus, our results suggest that directed inhibition of a single inducible phospholipase, PLA2G2D, in the lungs of older patients with severe respiratory infections is potentially an attractive therapeutic intervention to restore immune function.

Deficiency of RAMP1 attenuates antigen-induced airway hyperresponsiveness in mice.

Asthma is a chronic inflammatory disease affecting the lung, characterized by breathing difficulty during an attack following exposure to an environmental trigger. Calcitonin gene-related peptide (CGRP) is a neuropeptide that may have a pathological role in asthma. The CGRP receptor is comprised of two components, which include the G-protein coupled receptor, calcitonin receptor-like receptor (CLR), and receptor activity-modifying protein 1 (RAMP1). RAMPs, including RAMP1, mediate ligand specificity in addition to aiding in the localization of receptors to the cell surface. Since there has been some controversy regarding the effect of CGRP on asthma, we sought to determine the effect of CGRP signaling ablation in an animal model of asthma. Using gene-targeting techniques, we generated mice deficient for RAMP1 by excising exon 3. After determining that these mice are viable and overtly normal, we sensitized the animals to ovalbumin prior to assessing airway resistance and inflammation after methacholine challenge. We found that mice lacking RAMP1 had reduced airway resistance and inflammation compared to wildtype animals. Additionally, we found that a 50% reduction of CLR, the G-protein receptor component of the CGRP receptor, also ameliorated airway resistance and inflammation in this model of allergic asthma. Interestingly, the loss of CLR from the smooth muscle cells did not alter the airway resistance, indicating that CGRP does not act directly on the smooth muscle cells to drive airway hyperresponsiveness. Together, these data indicate that signaling through RAMP1 and CLR plays a role in mediating asthma pathology. Since RAMP1 and CLR interact to form a receptor for CGRP, our data indicate that aberrant CGRP signaling, perhaps on lung endothelial and inflammatory cells, contributes to asthma pathophysiology. Finally, since RAMP-receptor interfaces are pharmacologically tractable, it may be possible to develop compounds targeting the RAMP1/CLR interface to assist in the treatment of asthma.

Gs-coupled adenosine receptors differentially limit antigen-induced mast cell activation.

Mast cell activation results in the immediate release of proinflammatory mediators prestored in cytoplasmic granules, as well as initiation of lipid mediator production and cytokine synthesis by these resident tissue leukocytes. Allergen-induced mast cell activation is central to the pathogenesis of asthma and other allergic diseases. Presently, most pharmacological agents for the treatment of allergic disease target receptors for inflammatory mediators. Many of these mediators, such as histamine, are released by mast cells. Targeting pathways that limit antigen-induced mast cell activation may have greater therapeutic efficacy by inhibiting the synthesis and release of many proinflammatory mediators produced in the mast cell. In vitro studies using cultured human and mouse mast cells, and studies of mice lacking A(2B) receptors, suggest that adenosine receptors, specifically the G(s)-coupled A(2A) and A(2B) receptors, might provide such a target. Here, using a panel of mice lacking various combinations of adenosine receptors, and mast cells derived from these animals, we show that adenosine receptor agonists provide an effective means of inhibition of mast cell degranulation and induction of cytokine production both in vitro and in vivo. We identify A(2B) as the primary receptor limiting mast cell degranulation, whereas the combined activity of A(2A) and A(2B) is required for the inhibition of cytokine synthesis.

Adenosine increases nasal mucociliary clearance rate in mice through A2A and A2B adenosine receptors.

OBJECTIVES/HYPOTHESIS: Mucociliary clearance (MCC) is an important mechanism of host defense in the upper and lower respiratory tract. Impaired MCC plays a critical role in the development and perpetuation of chronic rhinosinusitis (CRS). The aim of this investigation was to determine the influence of adenosine on nasal MCC, and to determine the receptors mediating this physiology in vivo. STUDY DESIGN: Prospective study using an animal model. METHODS: Nasal MCC was measured by whole-nose scintigraphic acquisition in vivo. The effects of both endogenous and exogenous adenosine were investigated in wild-type and adenosine receptor knockout (A(2A)(-/-), A(2B)(-/-), A(2A)(-/-)A(2B)(-/-), and A(1)(-/- )A(3)(-/-)) mice. RESULTS: Exogenous adenosine aerosol robustly enhanced nasal MCC. The augmentation of MCC by adenosine was abolished in mice lacking both A(2A) and A(2B) receptors, but remained robust in mice lacking either A(2A) or A(2B) . Likewise, basal nasal MCC was reduced in mice lacking both the A(2A) and A(2B) receptors, but was statistically identical among wild-type mice and mice lacking either A(2A) or A(2B) . CONCLUSIONS: These findings indicate that activation of both G(s) -coupled adenosine receptors can accelerate nasal MCC. Targeting these receptors may represent a novel therapeutic approach for enhancing MCC in CRS.

Analysis of NLRP3 in the development of allergic airway disease in mice.

The contribution of NLRP3, a member of the nucleotide-binding domain leucine-rich repeat-containing (NLR) family, to the development of allergic airway disease is currently controversial. In this study, we used multiple allergic asthma models to examine the physiologic role of NLRP3. We found no significant differences in airway eosinophilia, histopathologic condition, mucus production, and airway hyperresponsiveness between wild-type and Nlrp3(-/-) mice in either acute (alum-dependent) or chronic (alum-independent) OVA models. In addition to the OVA model, we did not detect a role for NLRP3 in the development of allergic airway disease induced by either acute or chronic house dust mite Ag exposure. Although we did not observe significant phenotypic differences in any of the models tested, we did note a significant reduction of IL-13 and IL-33 in Nlrp3(-/-) mice compared with wild-type controls in the chronic OVA model without added alum. In all of the allergic airway disease models, the NLRP3 inflammasome-associated cytokines IL-1ß and IL-18 in the lung were below the level of detection. In sum, this report surveyed four different allergic asthma models and found a modest and selected role for NLRP3 in the alum-free OVA model. However, this difference did not greatly alter the clinical outcome of the disease. This finding suggests that the role of NLRP3 in allergic asthma must be re-evaluated.

MyD88 provides a protective role in long-term radiation-induced lung injury.

PURPOSE: The role of innate immune regulators is investigated in injury sustained from irradiation as in the clinic for cancer treatment or from a nuclear incident. The protective benefits of flagellin signaling through Toll-like receptors (TLR) in an irradiation setting warrant study of a key intracellular adaptor of TLR signaling, namely Myeloid differentiation primary response factor 88 (MyD88). The role of MyD88 in regulating innate immunity and Nuclear factor kappa-B (NF-κB)-activated responses targets this critical factor for influencing injury and recovery as well as maintaining immune homeostasis. MATERIALS AND METHODS: To examine the role of MyD88, we examined immune cells and factors during acute pneumonitic and fibrotic phases in Myd88-deficient animals receiving thoracic gamma (γ)-irradiation. RESULTS: We found that MyD88 supports survival from radiation-induced injury through the regulation of inflammatory factors that aid in recovery from irradiation. The absence of MyD88 resulted in unresolved pulmonary infiltrate and enhanced collagen deposition plus elevated type 2 helper T cell (Th2) cytokines in long-term survivors of irradiation. CONCLUSIONS: These results based only on a gene deletion model suggest that alterations of MyD88-dependent inflammatory processes impact chronic lung injury. Therefore, MyD88 may contribute to attenuating long-term radiation-induced lung injury and protecting against fibrosis.

IL-4 amplifies the pro-inflammatory effect of adenosine in human mast cells by changing expression levels of adenosine receptors.

Adenosine inhalation produces immediate bronchoconstriction in asthmatics but not in normal subjects. The bronchospastic effect of adenosine is largely mediated through adenosine-induced mast cell activation, the mechanism of which is poorly understood due to limitations in culturing human primary mast cells. Here, we show that human umbilical cord blood -derived mast cells incubated with the Th2 cytokine IL-4 develop increased sensitivity to adenosine. Potentiation of anti-IgE- induced and calcium ionophore/PMA-induced degranulation was augmented in mast cells cultured with IL-4, and this effect was reduced or abolished by pre-treatment with A(2B)siRNA and selective A(2B) receptor antagonists, respectively. IL-4 incubation resulted in the increased expression of A(2B) and reduced expression of A(2A) adenosine receptors on human mast cells. These results suggest that Th2 cytokines in the asthmatic lung may alter adenosine receptor expression on airway mast cells to promote increased responsiveness to adenosine.

[A pilot investigation on serum protein fingerprinting of nasopharyngeal carcinoma].

OBJECTIVE: To establish a preliminary foundation for developing a serum proteomics diagnostic model of nasopharyngeal carcinoma (NPC) by comparing the differences in serum protein fingerprints between patients with NPC and healthy subjects and between different types of NPC. METHODS: The serum samples of 41 patients with different types of NPC and 20 healthy subjects were collected. Surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) were used to detect the blood samples to obtain serum protein mass spectrum, i.e. serum protein fingerprinting. Biomarker Wizard and Biomarker Patterns system software were used to compare the differences in serum protein mass spectrum between NPC patients and healthy subjects and between different types of NPC, and to screen out the NPC-related serum proteins. RESULTS: Compared with the healthy control, NPC patients emerged 9 very prominent protein peaks (P < 0.001), with the combined differential peaks. No significant difference was found in relative amount of serum proteins with different molecular mass between different types of NPC (P > 0.05). CONCLUSIONS: The serum marker proteins and specific protein fingerprints of NPC can be screened out by SELDI-TOF-MS, which could be used to develop a serum proteomics model for clinical screening and early diagnosis of NPC.

The chemokine, CCL3, and its receptor, CCR1, mediate thoracic radiation-induced pulmonary fibrosis.

Patients receiving thoracic radiation often develop pulmonary injury and fibrosis. Currently, there are no effective measures to prevent or treat these conditions. We tested whether blockade of the chemokine, CC chemokine ligand (CCL) 3, and its receptors, CC chemokine receptor (CCR) 1 and CCR5, can prevent radiation-induced lung inflammation and fibrosis. C57BL/6J mice received thoracic radiation, and the interaction of CCL3 with CCR1 or CCR5 was blocked using genetic techniques, or by pharmacologic intervention. Lung inflammation was assessed by histochemical staining of lung tissue and by flow cytometry. Fibrosis was measured by hydroxyproline assays and collagen staining, and lung function was studied by invasive procedures. Irradiated mice lacking CCL3 or its receptor, CCR1, did not develop the lung inflammation, fibrosis, and decline in lung function seen in irradiated wild-type mice. Pharmacologic treatment of wild-type mice with a small molecule inhibitor of CCR1 also prevented lung inflammation and fibrosis. By contrast, mice lacking CCR5 were not protected from radiation-induced injury and fibrosis. The selective interaction of CCL3 with its receptor, CCR1, is critical for radiation-induced lung inflammation and fibrosis, and these conditions can be largely prevented by a small molecule inhibitor of CCR1.

[Mast cell and its relation to eosinophilic inflammation in CRSsNP].

OBJECTIVE: To observe the pathologic characteristics, and investigate mast cell and its activation in chronic rhinosinusitis without nasal polyps (CRSsNP) and their relations with eosinophilic inflammation. METHOD: HE stain was used to observe tissue features and count total inflammatory cells, mononuclear cells, plasma cells and eosinophilic in lamina propria of CRSsNP and inferior turbinate. Toluidine blue stain and immunohistochemical stain for tryptase were used to detect mast cell and its activation respectively in CRSsNP and control, and their corelations with tissue eosinophilia were analysed. RESULT: CRSsNP has increased total inflammatory cells, mononuclear cells and plasma cells but comparable eosinophilic and lamina propria glands compared with inferior turbinate. Mast cells corelated with activated mast cells, but there was no difference between CRSsNP and control for both of them and there were no corelation between mast cell and its activation with tissue eosinophilia. CONCLUSION: CRSsNP has more serious inflammation but no more mast cell and its activation and eosinophil compared with inferior turbinate, and there were no corelations between mast cell and its activation with eosinophil count which suggests that mast cell and eosinophilic inflammation mediated by it may not play an important role in the pathogenesis of CRSsNP.