IL-21 induces pyroptosis of Treg cells via Akt-mTOR-NLRP3-caspase 1 axis in eosinophilic chronic rhinosinusitis.

BACKGROUND: Regulatory T (Treg) cells, which prevent inflammation-induced eosinophil infiltration, are deficient in nasal polyps (NPs) in patients with eosinophilic chronic rhinosinusitis (ECRS). It is concomitant with loss of Foxp3 after certain inflammatory stimuli. OBJECTIVE: We sought to determine the inflammatory cytokines involved in inducing the loss of Treg cells in NPs. METHODS: The abundance of cytokines in ECRS patients or mice were tested using ELISA, immunochemistry, immunofluorescence, quantitative reverse transcription PCR (qPCR), and/or flow cytometry. Expression of eosinophil cationic protein (ECP), CD4+ T cells, IL-4, and IL-17A and eosinophils in nasal mucosa of mouse model was investigated by immunochemistry, immunofluorescence, and hematoxylin and eosin staining. The percentage and death of induced Treg (iTreg) cells, source of IL-21 in NPs from ECRS and non-ECRS patients, and abundance of different systemic phenotypes of CD4+ T cells in a mouse model were studied by flow cytometry. Western blot analysis, scanning, and transmission electronic microscopy were used to detect pyroptosis of iTreg cells. RESULTS: IL-21 was highly expressed in nasal mucosa of ECRS patients and mice, causing pyroptosis and preventing development of iTreg cells in vitro. The elevated IL-21 in NPs from ECRS patients was mainly produced by CD3+ T cells, including T follicular helper, T peripheral helper, TH2, and TH17 cells and CD3+CD4- T cells. T peripheral helper cells and CD3+CD4- T cells were the predominant source of IL-21 in NPs from non-ECRS patients. Blocking IL-21/IL-21R signaling significantly reduced the number of eosinophils and CD4+ T cells along with ECP, IL-4, and IL-17A expression in the nasal mucosa of ECRS mice. It also increased Treg cell percentage and systemically decreased TH2 and TH17 ratios. Akt-mTOR inhibition prevented IL-21-induced pyroptosis in human and mouse iTreg cells. CONCLUSION: Elevated IL-21 drives pyroptosis and prevents Treg cell development in ECRS patients. IL-21 induced pyroptosis via activating Akt-mTOR-NLRP3-caspase 1 signaling.

Type 2 inflammation suppression by T-regulatory cells attenuates the eosinophil recruitment in mucosa of chronic sinusitis.

Type 2 inflammation and eosinophilic infiltration are prominent pathologic features of chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of the present study was to determine the roles of Tregs in controlling type 2 inflammation and inhibiting eosinophilic infiltration in CRSwNP. A total of 134 nasal polyps, 67 ostiomeatal complex from chronic rhinosinusitis (CRS) and 62 normal nasal tissues from controls were collected to study the enumeration and function of Tregs cells and the expressions of cytokine profiles via immunofluorescence staining, flow cytometry, qRT-PCR, ELISA, and/or H&E staining. The effects of Tregs on type2 and type3 inflammations were determined in an eosinophilic chronic sinusitis (ECRS) mice model. It was confirmed that the CRSwNP displayed the features of Th2 and Th17 cells-mediated inflammation, accompanying by an increased level of eosinophilic infiltration and the eosinophil cationic protein (ECP), with a decreased frequency of Treg cells. Furthermore, the percentages of CD4+CD25+CD127lowTreg and CD4+CD25+Foxp3+Treg were only decreased in the polyps of CRSwNP but not in the paired peripheral blood. The CRSwNP possessed the decreased Nrp1+Tregs, Helios+Treg, and low TGF-ß and interleukin (IL)-10 expressions in Tregs. The ECRS mice showed similar inflammatory characteristics to CRSwNP patients. The adoptive transfer of CD4+CD25+Foxp3+ Treg cells significantly decreased the inflammatory cytokines, eosinophilic chemotactic factors in the mucosa of the ECRS mice without alteration of the immune balance in the peripheral blood and spleen. In conclusion, CRSwNP showed high type 2 and type3 inflammation and defective Tregs. The induced regulatory T cell (iTreg) may correct the imbalance between immune tolerance and effect via limiting the eosinophil recruitment of mucosa in CRSwNP.

γδT cells contribute to type 2 inflammatory profiles in eosinophilic chronic rhinosinusitis with nasal polyps.

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRS) is a condition linked with type 2 inflammation, poor treatment outcomes, and high recurrence tendency. Although γδT cells have been reported to induce type 2 immune responses and eosinophilic infiltration in several diseases, their role in ECRS has not been fully explored. We aimed to evaluate the association of γδT cells with the type 2 inflammatory profiles in ECRS. Nasal tissue samples obtained from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) (51 eosinophilic and 48 non-eosinophilic), 50 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 58 control subjects were examined for γδT cells, inflammatory markers and eosinophils using HE, RT-qPCR, ELISA, immunofluorescence, and flow cytometry. In parallel, studies were also conducted in an ECRS murine model induced by anti-γδT cells neutralizing antibody administration. γδT cells expression was significantly increased in tissues from patients with ECRS compared with non-ECRS, CRSsNP and control subjects. Moreover, inflammatory markers including type 2 proinflammatory cytokines (IL-4, IL-5, IL-13), GATA3, eosinophil cationic protein (ECP), and eotaxin levels were also increased in nasal tissues of patients with ECRS, and Vγ1+ γδT cells mRNA expression was positively correlated with type 2 cytokines, GATA3, and ECP. In the ECRS murine model, anti-Vγ1+ γδT antibody treatment reduced the infiltration of eosinophils and expression of type 2 cytokines, GATA3, and ECP in nasal mucosae. In conclusion, the results of the present study suggest that γδT cells play a crucial role in the type 2 inflammatory profiles and nasal tissue eosinophilic infiltration in patients with ECRS.

Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy.

BACKGROUND: The Mre11-Rad50-Nbs1 (MRN) complex is well known for its crucial role in initiating DNA double strand breaks (DSBs) repair pathways to resistant irradiation (IR) injury and thus facilitating radioresistance which severely reduces radiocurability of nasopharyngeal cancer (NPC). Targeting native cellular MRN function would sensitize NPC cells to IR. METHODS: A recombinant adenovirus containing a mutant Rad50 gene (Ad-RAD50) expressing Rad50 zinc hook domain but lacking the ATPase domain and the Mre11 interaction domain was constructed to disrupt native cellular MRN functions. The effects of Ad-RAD50 on the MRN functions were assessed in NPC cells lines using western blot, co-immunoprecipitation and confocal microscopy analyses. The increased radiosensitivity of transient Ad-RAD50 to IR was examined in NPC cells, including MTT assay, colony formation. The molecular mechanisms of radiosensitization were confirmed by neutral comet assay and western bolts. Nude mice subcutaneous injection, tumor growth curve and TUNEL assay were used to evaluate tumor regression and apoptosis in vivo. RESULTS: Rad50 is remarkably upregulated in NPC cells after IR, implying the critical role of Rad50 in MRN functions. The transient expression of this mutant Rad50 decreased the levels of native cellular Rad50, Mre11 and Nbs1, weakened the interactions among these proteins, abrogated the G2/M arrest induced by DSBs and reduced the DNA repair ability in NPC cells. A combination of IR and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage, prevented proliferation and cell viability. Furthermore, Ad-RAD50 sensitized NPC cells to IR by causing dramatic tumor regression and inducing apoptosis in vivo. CONCLUSION: Our findings define a novel therapeutic approach to NPC radiosensitization via targeted native cellular Rad50 disruption.

[Characteristics and therapeutic strategies of Pott's puffy tumor].

Objective:To explore the characteristics and therapeutic strategies of Pott's puffy tumor（PPT）. Methods:The clinical data of two patients with PPT were retrospectively analyzed and combined with the literature, focusing on the comprehensive analysis of perioperative diagnosis and treatment strategies. Both patients underwent muti-disciplinary treatment, including timely administration of sufficient antibiotics capable of penetrating the blood-brain barrier. Early removal of PPT lesions was performed using a combined internal and external approach under nasal endoscopic guidance. Results:After standardized perioperative management, the symptoms of the two patients were completely relieved, with no recurrence after one=year follow=up. Postoperative complications such as frontal pain, numbness, local depression, or scar hyperplasiawere not present. Conclusion:PPT, being relatively rare and severe, requires careful attention. Key strategies for standardized perioperative management include multi-disciplinary consultation, timely and adequate antibiotic administration, and surgical intervention using a combined intranasal and extranasal endoscopic approach for lesion removal.

[Based on CT imaging, surgical approach selection for frontal and ethmoid sinus osteoma].

Objective:To investigate the criteria for selecting surgical approaches for frontal and ethmoid sinus osteomas of different locations and sizes on CT imaging. Methods:Using sagittal and coronal CT images, the following lines were delineated: the F-line（a horizontal line passing nasofrontal beak）, the M-line（a vertical line passing paries medialis orbitae）, and the P-line（a vertical line passing the center of the pupil）. Classification of frontal and ethmoid sinus osteomas was based on their relationship with these lines. Appropriate surgical approaches were selected, including pure endoscopic approaches, endoscopic combined with eyebrow incision approach, and endoscopic combined with coronal incision approach. This method was applied to a single center at the Third Affiliated Hospital of Sun Yat-sen University for endoscopic resection of frontal and ethmoid sinus osteoma. Case Data: Sixteen cases of ethmoid sinus osteomas were treated from January 2020 to September 2023. Among these cases, there were 9 males and 7 females, with ages ranging from 18 to 69 years, and a median age of 48 years. Results:Thirteen cases underwent pure endoscopic resection of the osteoma, while in three cases, a combined approach was utilized. Among the combined approach cases, two exceeded both the M-line and the F-line but did not cross the P-line; therefore, they underwent endoscopic combined with eyebrow incision approach. One case exceeded all three lines and thus underwent endoscopic combined with coronal incision. In all cases, complete resection of the osteoma was achieved as per preoperative planning, and none of the patients experienced significant postoperative complications. Conclusion:For frontal and ethmoid sinus osteomas, it is advisable to perform a thorough preoperative radiological assessment. Based on the size of the osteoma and its relationship to the three lines, an appropriate surgical approach should be chosen to optimize the diagnostic and treatment plan.

Improved perioperative quality of life in endoscopic sinus surgery by application of enhanced recovery after surgery.

Background: Endoscopic sinus surgery (ESS) has been the definitive treatment for chronic rhinosinusitis (CRS), but the complications caused perioperatively may affect patients' quality of life (QoL). This study aims to evaluate the effects of enhanced recovery after surgery (ERAS) on improving perioperative QoL in ESS. Materials and methods: Seventy-four patients with chronic rhinosinusitis with nasal polyps (CRSwNP) met the criteria for inclusion. Participants undergoing ESS were randomly divided into an ERAS group and a control group, and QoL assessment was performed using the Chinese version of the 22-item Sinonasal Outcomes Test (SNOT-22). Measurements were administered at baseline, and on postoperative day 1 (POD1), POD3 and POD6. Complications such as nausea/emesis, hemorrhage, aspiration and dizziness were also recorded. Results: The preoperative global SNOT-22 scores (mean ± SD) were 39.89±4.86 in the ERAS group and 40.52±3.61 in the control group (t=0.643, P=0.522). On POD1, the global SNOT-22 scores increased significantly to 51.77±5.59 and 62.02±3.86 (t=9.218, P<0.01), and on POD3 they increased to 48.22±6.22 and 51.11±5.14, respectively (t=2.179, P<0.05). However, the scores recovered to 39.39±4.73 and 40.13±3.31 in the respective groups on POD6, which were lower than but not statistically significant different from the baseline (t=0.786, P=0.434). There were statistically significant improvements across all subdomains of SNOT-22 for patients in the two groups only in POD1 (all P<0.05). The ERAS group did not have an increased incidence of complications such as nausea/emesis (χ 2=0.223, P>0.05), hemorrhage, aspiration and dizziness compared to the control group. Conclusion: ERAS could improve perioperative QoL in patients with CRSwNP undergoing ESS, and SNOT-22 can be used for ERAS evaluation as a patients' outcome report.

Enhanced recovery after surgery protocols in functional endoscopic sinus surgery for patients with chronic rhinosinusitis with nasal polyps: a randomized clinical trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are a series of perioperative care to optimize preoperative preparation, prevent postoperative complications, minimize stress, and speed up recovery. This study aimed to assess the impact of ERAS protocols for functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: One hundred and two patients with CRSwNP undergoing FESS were randomly divided into the ERAS group and the control group. The outcomes of the Self-Rating Anxiety Scale (SAS), Visual Analogue Scale (VAS), Medical Outcomes Study Sleep Scale (MOS-SS) and Kolcaba Comfort Scale Questionnaire (GCQ) were determined in both groups. The serum levels of C-reactive protein (CRP) were compared preoperatively and 24 hours postoperatively. RESULTS: The ERAS group had a significantly better SAS scores than did the control group (28 [24, 35] vs. 43 [42, 47], Z = 5.968, P < 0.001). The rhinalgia and headache scores at 2, 24 and 48 hours postoperatively were lower in the ERAS group than that in the control group (all P < 0.001). The outcomes of the MOS-SS (43 [42, 39] vs. 28 [22, 35], Z = 7.071, P < 0.001) and GCQ (76 [68, 87] vs. 64 [50, 75], Z = 4.806, P < 0.001) were significantly different between the two groups. No significant difference was found in the preoperative CRP levels between the two groups (1.3 [0.6, 2.8] vs. 0.5 [0.5, 1.2], Z = 3.049, P > 0.05); However, the CRP level in 24 hours postoperatively was significantly lower in the ERAS group than that in the control group (2.5 [1.4, 3.9] vs. 6.6 [3.8, 9.0], Z = 5.027, P < 0.001). The incidence rates of complications, such as nausea/emesis (χ = 0.343, P > 0.05), hemorrhage, aspiration and tumble, were not increased in the ERAS group compared with those in the control group. The ERAS group had a significantly shorter length of hospital stay (5 [4, 5] days vs. 8 [8,9] days, Z = 8.939, P < 0.001) and hospitalization expenses ($ 2670 [2375, 2740] vs. $3129 [3116, 3456], Z = 8.514, P < 0.001). CONCLUSIONS: ERAS protocols might optimize FESS for patients with CRSwNP by reducing psychological and physical stress, shortening the length of hospital stay and lowering hospitalization expenses without increasing postoperative complications. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR1800015791; http://www.chictr.org.cn/showproj.aspx?proj=26872.

IL-19 Up-Regulates Mucin 5AC Production in Patients With Chronic Rhinosinusitis via STAT3 Pathway.

The mucin gene, MUC5AC, is highly expressed both in chronic respiratory inflammatory diseases and inflammatory bowel disease where mucin secretion is regulated by members of the interleukin IL-20 subfamily. This study was conducted to determine the roles and mechanisms of IL-19, a member of the IL-20 subfamily, in regulating MUC5AC production in chronic rhinosinusitis (CRS). We analyzed the expression of mucin and MUC5AC in the nasal mucosa of patients with CRS through periodic acid Schiff (PAS) staining and immunohistochemical examination. Real-time quantitative PCR, ELISA, confocal microscopy and western blotting were used to measure MUC5AC expression in primary human nasal epithelium cells (PHNECs) stimulated with recombinant human IL-19 (rhIL-19), IL-19 receptor siRNA transfection or a control. The involvement of the STAT3 signaling pathway was examined using cryptotanshinone (CRY, an inhibitor of STAT3). Mucin and MUC5AC were significantly increased in mucosa of CRS patients with/without nasal polyps compared to mucosa isolated from controls who had no CRS, but there were no significant differences between these two groups. Pretreatment with rhIL-19 up-regulated the expression of MUC5AC levels in PHNECs. Knockdown of IL-20R2 and pretreatment with CRY attenuated MUC5AC production induced by rhIL-19. We propose that IL-19 up-regulates MUC5AC-induced mucin production via the STAT3 pathway in CRS, highlighting the important role IL-19 may play in mucin production in chronic respiratory diseases.

Tc17/IL-17A Up-Regulated the Expression of MMP-9 via NF-κB Pathway in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the upper airways involving nasal cavity and sinus. Deriving both from its clinical complexity with protean clinical manifestations as well its pathogenetic heterogeneity, the molecular mechanisms contributing to the pathogenesis of CRS remain unclear, and attract a wide interest in the field. Current evidences indicate that IL-17A is highly expressed in chronic rhinosinusitis with nasal polyps (CRSwNP). However, its pathogenetic role in regulation of tissue remodeling of CRSwNP remains unknown. The present study aimed to investigate the cellular origins and functions of IL-17A cytokine in CRSwNP, and further determined whether IL-17A could affect the expression of metalloproteinases (MMPs), the remodeling factors of CRSwNP. The results showed that the expression of IL-17A was upregulated in nasal tissues of patients with CRSwNP compared to those with chronic rhinosinusitis without nasal polyps (CRSsNP) and controls. CD8+ cytotoxic T lymphocytes (Tc) were major IL-17A producers in nasal tissues of CRSwNP. Interleukin (IL)-17-producing CD8+ T cells (Tc17) was significantly higher in nasal tissues of CRSwNP than CRSsNP and controls. Nonetheless, no difference was observed among the IL-17A in peripheral blood lymphocytes of these three groups. Moreover, in the same patients, IL-17A expression was negligible in lymphocytes of peripheral blood when compared with nasal tissues. Increased gene and protein expression of MMP-7 and MMP-9 in patients with CRSwNP compared with controls were observed. In CRSwNP samples, IL-17A receptor (IL-17AR) co-localized with MMP-9 and they were mainly expressed in the epithelial cells. MMP-9 expression was up-regulated both in Primary human nasal epithelial cells (PHNECs) and a nasal epithelial cell line (RPMI 2650) by IL-17A treatment, and diminished by anti-IL-17AR treatment. Furthermore, IL-17A promoted the expression of MMP-9 by activating the NF-κB signal pathway. Thus, our results have revealed a crucial role of IL-17A and Tc cells on pathogenesis and tissue remodeling of CRSwNP.

[The preparation of recombinant adenovirus Ad-Rad50-GFP and detection of the optimal multiplicity of infection in CNE1 transfected hv Ad-Rad50-GFP].

OBJECTIVE: The optimal multiplicity of infection (MOI) of the recombinant adenovirus Ad-Rad50-GFP carrying a mutant Rad50 gene expression region on the cell growth of nasopharyngeal carcinoma and the viral amplification efficiency of CNE1 cell infected by this adenovirus were studied. METHOD: The biological titer of Ad-Rad50-GFP was measured by end point dilution method. The impact of recombinant adenoviral vector transfection on the growth of CNE1 cells was observed by cell growth curve. Transfection efficacy of recombinant adenoviral vector was observed and calculated through fluorescence microscope. The expression f mutant Rad50 in the Ad-Rad50-GFP transfected CNE1 cells with optimal MOI was detected by Western Blot after transfection. RESULT: The biological titer of Ad-Rad50-GFP was 1.26 x 10¹¹ pfu/ml. CNE1 cell growth was not influenced significantly as they were transfected by recombinant adenoviral vector with MOI less than 50. Transfection efficacy of recombinant adenoviral vector was most salient at 24 hours after transfection, with the high expression of mutant Rad50, and the efficiency still remained about 70% after 72 hours. CONCLUSION: Recombinant adenoviral vector Ad-Rad50-GFP could transfect CNE1 cells as well as result in the expression of mutant Rad50 in CNE1 cells effectively. MOI = 50 was the optimal multiplicity of infection of CNE1 cells transfected by recombinant adenoviral vector Ad-Rad50-GFP.

The Role of Tracheostomy in Anaplastic Thyroid Carcinoma.

Even though management of thyroid cancer is generally standardized and has an overall excellent long-term outcome, anaplastic thyroid cancer (ATC) continues to be a major diagnostic and therapeutic challenge. ATC is an uncommon thyroid malignancy with a poor prognosis. American Thyroid Association guidelines acknowledge the complexity of airway management in these patients. We studied the literature with the aim of providing guidance in airway management in ATC. Tracheotomy can facilitate completion of palliative treatment in those patients with ATC and stridor. Given the short life expectancy of these patients, a balanced decision must be made regarding the role and timing of tracheotomy.

Management of lymph node metastases from an unknown primary site to the head and neck (Review).

Cancer of unknown primary site (CUP) is an intriguing clinical phenomenon found in ~3-9% of all head and neck cancers. It has not yet been determined whether CUP forms a distinct biological entity with specific genetic and phenotypic characteristics, or whether it is the clinical presentation of metastasis in patients with an undetected primary tumor and no visible clinical signs. The treatment of patients with cervical lymph node metastases from CUP remains controversial, due to the lack of randomized clinical trials comparing different treatment options. Consequently, treatment is currently based on non-randomized data and institutional policy. In the present review, the range and limitations of diagnostic procedures are summarized and an optimal diagnostic work-up is recommended. The initial preferred diagnostic procedures include fine-needle aspiration biopsy (FNAB) and imaging. Although neck dissection followed by postoperative radiotherapy is the the most generally accepted approach, other curative options may be used in certain patients, such as neck dissection alone, nodal excision followed by postoperative radiotherapy, or radiotherapy alone. There remains controversy regarding target radiation volumes, ranging from ipsilateral neck irradiation to prophylactic irradiation of all the potential mucosal sites and both sides of the neck. When no primary lesion is identified with imaging and endoscopy in patients without history of smoking and alcohol abuse, molecular profiling of an FNAB sample for human papillomavirus and/or Epstein-Barr virus is required.

[Effects of tetrandrine on enhancing radiosensitivity of human nasopharyngeal carcinoma cells].

OBJECTIVE: To study the effect and mechanism of tetrandrine (Tet) on enhancing radiosensitivity of human nasopharyngeal carcinoma cell lines in vitro. METHODS: CNE1 and CNE2 were exposed to radiation with or without Tet, the DNA damage of the cells were evaluated by neutral comet electrophoresis, and cell cycle and apoptosis were analyzed by flow cytometry. RESULTS: The mean tail movements (TM) of CNE1 treated with radiation or radiation plus Tet were (7.13 ± 3.70) (X(-) ± s) and (13.61 ± 5.45), respectively (t = 2.784, P < 0.05), and TM of CNE2 treated with radiation or radiation plus Tet were (11.52 ± 4.04) and (18.85 ± 6.18), respectively (t = 3.089, P < 0.05). With the exposure to radiation or radiation plus Tet, the percentages of CNE1 in G2 phases were (42.62 ± 2.07)% and (17.02 ± 1.87)%, respectively (t = 23.173, P < 0.01), and the percentages of CNE2 in G2 phases were (34.82 ± 2.74)% and (19.64 ± 4.82)%, respectively(t = 16.500, P < 0.01). There was no significant difference in the apoptosis rates between the cells treated with radiation or radiation plus Tet regardless of CNE1 (17.24 ± 0.99)% vs (19.11 ± 1.24)%, and CNE2 (16.68 ± 0.27)% vs (18.51 ± 2.41)% (P > 0.05). CONCLUSIONS: Tet can enhance radiosensitivity of human nasopharyngeal carcinoma cell lines. The mechanism could be related to abrogation of radiation-induced G2/M arrest and reduction of double-strand break repair capacity.

[Radiobiological characteristics and MRN complex expression of human nasopharyngeal carcinoma cell lines].

OBJECTIVE: To study the radiobiological characteristic of human nasopharyngeal carcinoma cell lines CNE1 and CNE2 and the changes in expression MRN (Mre11-Rad50-Nbs1) complex in the cell lines exposed to irradiation. METHODS: CNE1 and CNE2 were irradiated by a linear accelerator. Radiobiological characteristics were detected by colony assay and MTT assay. MRN complex expression were examined by Western blot. RESULTS: Surviving fraction at 2 Gy (SF2), quasi-threshold Dose (Dq), and mean lethal dose (Do) of CNE1 were 0.56, 1.449 Gy and 1.480 Gy; SF2, Dq, and Do of CNE2 were 0.44, 0.776 Gy and 1.685 Gy, respectively. Survival fraction of CNE1 at the day 6 after 4 Gy irradiation was 0.59 and that of CNE2 was 0.79 when compared with control, with the up-regulated expressions of Rad50 in CNE1 and Mre11, Rad50 and Nbs1 in CNE2 (P < 0.05). CONCLUSIONS: CNE1 and CNE2 were sensitive to radiation, but there were radioresistance cells in CNE2. The expressions of some components of MRN complex were up-regulated to repair DNA lesions induced by radiation.