Objective:To explore the mechanisms of the inhalation of atomized 1.0% anti-IL-1βand TNF-αimmunoglobulin yolk ( IgY) on treating guinea pigs with allergic asthma induced by the inhalation of aerosolized ovalbumin ( OVA).Methods:Healthy guinea pigs were randomly divided into the normal controls ( group C ) , the allergic asthma model group ( group M )-treated by the inhalation of atomized ovalbumin ( OVA ) , the inhalation of atomized 1.0% anti-IL-1βand TNF-αimmunoglobulin yolk ( IgY ) treatment group (group Z1)-treated asthma model guinea pigs by the inhalation of atomized 1.0% anti-IL-1βand TNF-αIgY,and positive control the inhalation of atomized budesonide treatment group (group Z2)-treated asthma model guinea pigs by the inhalation of atomized budesonide.The blood was gotten by cardiac puncture and the bronchoalveolar lavage fluid ( BALF ) was collected by bron-choalveolar lavage at 2 h,4 h,8 h and 24 h after the last time atomization.The inflammatory cells in the peripheral blood ( PB) were counted by methylene blue and eosin staining.Cytokine concentrations of IL-1β,IL-4,IL-6,IL-8,IL-13,IL-16,TNF-α,TGF-β1 and IgE in the plasma and bronchoalveolar lavage fluid (BALF) were measured using an enzyme-linked immunosorbent assay (ELISA).Results:In PB,eosinophils was decreased from 2 h to 8 h in group Z1 compared to group M.In plasma,the levels of IL-1βat 4 h and 24 h,IL-16 at 2 h,4 h and 24 h,TGF-β1 from 4 h to 24 h and IgE at 24 h,as well as the levels of IL-1βand TNF-αfrom 2 h to 8 h,IL-4,IL-6,IL-8 and IL-13 from 4 h to 24 h,IL-16 at 8 h,and TGF-β1 and IgE from 4 h to 8 h,especially the level of IL-1βand TNF-αstarting at 2 h,in BALF were significantly reduced in group Z 1 compared to group M ( P<0.05 ).The levels of IL-1βand TNF-αwere positively cor-related with that of IL-4,IL-6,IL-8,IL-13,IL-16,TGF-β1 and IgE (P<0.05).Conclusion: The inhalation of aerosolized anti-IL-1βand TNF-αIgY effectively alleviates inflammatory responses in guinea pigs with allergic asthma induced by aerosolized OVA inhalation may be due to the significant decrease in the levels of various allergic inflammatory cytokines .

Objective:To investigate therapeutic mechanism of immunoglobulin Yolk (IgY) against tumour necrosis factor alpha ( TNF-α) and interleukin-1 beta ( IL-1β) in guinea pigs with allergic rhinitis.Methods: Hartley guinea pigs were randomly divided into the control group (group C,n=17),the allergic rhinitis model group (group M,n=27),the 0.1%anti-TNF-αand IL-1βIgY treating group (group Z1,n=21) and the fluticasone propionate treating group (group Z2,n=21).The allergic rhinitis model in guinea pigs was established using ovalbumin.After treatment for 2 h,4 h,8 h,nose and bronchial lung were lavaged using 0.9%saline, the nasal lavage fluid (NLF) and bronchoalveolar lavage fluid (BALF) were collected,the precipitated cells were stained using Wright′s,the nasal mucosa and lung tissues were stained using methylene blue and eosin (HE),and TNF-α,IL-1β,IL-5 and IL-33 in nasal mucosa and lung tissues were stained using immunohistochemistry.Results:There were a large amount of eosinophils and more serious inflammation responses in nasal mucosa in the M group compared with the Z 1 and Z2 groups.In the lung tissues,there were more alveolar tube damage ,pulmonary interstitial edema ,interval thickening ,thickening of bronchial smooth muscle and inflammation cell in-filtration in the M group compared with the Z 1 and Z2 groups.The eosinophils ,lymphocytes and neutrophils were significantly decreased in NLF and BALF in the Z1 and Z2 groups compared with the M group (P<0.05).The expressions of IL-1βand TNF-αfrom 2 h to 8 h and IL-5 and IL-33 from 4 h to 8 h significantly decreased in the nasal mucosa and lung tissues in the Z 1 group compared with the M group ( P<0.05 ).Conclusion:The allergic rhinitis in guinea pigs accompany with the allergic asthma.The inhibitory capacity of anti-TNF-αand IL-1βIgY on pathological responses in guinea pigs with allergic rhinitis may be due to the significant decrease in the infiltration of eosinophils and the expressions of inflammatory cytokines in the nasal mucosas and lung tissues .

Objective To investigate the mechanism of hypoxia regulate osteopontin (OPN) secreting by mature dendritic cells (mDCs). Methods CD14 + cells were enriched using anti-CD14 immunomagnetic beads, for inducing to mDCs, CD14 + cells were cultured with GM-CSF and IL-4 in hypoxia or normoxiain vitro. Concentration of OPN and TGF-β1 in supernatant were detected by sandwich ELISA, OPN mRNA detected by RT-PCR. Approach regulating function of A2 R in expressing of OPN by mDCs by using NECA (surrogate of adenosine), A2R agonist (CGS21680), A2R antagonist (SCH58261) and investigate role of TGF-β1 in this process by using rhTGF-β1 and anti-TGF-β1 Ab. Results Hypoxia inreased the level of OPN and OPN mRNA in mDCs, and this effect could be reversed by A2 R antagonist. Under normoxia,both NECA and A2R agonist (CGS21680) could upregulate the level of OPN and OPN mRNA in mDCs significantly, but this positive effect could be reversed by A2 R antagonist. A2 R played a role in regulating TGF-β1, and confirmed TGF-β1 involved in regulation of OPN by using rhTGF-β1 and anti-TGF-β1 Ab. Conclusion High adenosine induce the generation of TGF-β1 through the A2R on mDCs, and then TGF-β1 raise the OPN secreting by mDCs.

Objective To evaluate the short-term efficacy and adverse events of pencil beam scanning proton and carbon ion therapy in the treatment of chordoma and chondrosarcoma of the head and neck.Methods Between July 2014 and July 31,2017,61 patients with chordoma and chondrosarcoma of the head and neck receiving proton and heavy ion therapy as the first course of radiotherapy were enrolled.Among them,45 patients were diagnosed with chordoma and 16 cases of chondrosarcoma,39 male and 22 female.The median age was 38 years old (range:14-70 years).The median maximum tumor diameter was 4.1 cm (range:0-8.6 cm).The clivus and the cervical spine were the primary tumor sites.Results Eight patients received proton therapy,21 patients were treated with proton combined with carbon ion therapy and 32 patients received carbon ion therapy.All patients successfully completed the planned radiotherapy.The medial follow-up time was 21 months (range:7-47 months).No grade 3-4 acute toxicity was observed.Only one patient suffered from radiation-induced temporal lobe injury.The 2-year progression-free survival (PFS)and overall survival (OS) were 91％ and 100％.Conclusions Pencil beam scanning proton and heavy ion therapy yields relatively favorable short-term outcomes in the treatment of chordoma and chondrosarcoma of the head and neck.Nevertheless,the long-term clinical efficacy and safety remain to be investigated during follow-up.

Objective:To evaluate the short-term tumor control and toxicity of recurrent skull base and cervical spine chordoma and chondrosarcoma in patients treated with pencil beam scanning proton and heavy ion therapy.Methods:Between June 30 th, 2014 and July 30 th, 2018, a total of 45 skull base and cervical spine chordoma ( n=39) and chondrosarcoma ( n=6) patients (28 males and 17 females; mean age at initial presentation of 44 years, range, 14-76 years) were treated in our center for the course of radiotherapy. The median maximum tumor volume was 57 cm 3 (range, 6.6-231.7 cm 3). There were 31 post-operative recurrent patients and 14 post-operative and post-radiated recurrent patients. One patient received proton therapy, 21 patients received combined proton and carbon ion therapy, 23 patients received carbon ion therapy. Results:All patients completed the whole course of the treatment. The median follow-up time was 29 months (range: 8-57 months), the 2-year overall survival (OS), local control (LC), and progression-free survival (PFS) were 82.7%, 85.3%, and 73.8%, respectively. There were no other grade 3-4 acute or late radiation-induced toxicity except one grade 3 acute mucositis. The 2-year OS rates for patients after first-time radiation vs. re-irradiation were 96.2% and 50.3% ( χ2=16.969, P<0.05). Conclusions:The short-term outcomes of pencil beam scanning proton and heavy ion therapy for recurrent skull base and cervical spine chordoma and chondrosarcoma is favorable. Further study is needed for long-term efficacy and safety.

Objective:To investigate the safety and efficacy of proton beam radiation therapy (PBRT) in patients with World Health Organization (WHO) GradeⅠ/Ⅱ meningioma.Methods:Twenty-six patients with intracranial ( n=8, 30.8%) or skull-base ( n=18, 69.2%) meningioma treated with PBRT from May 2015 to October 2018 were analyzed retrospectively. The median age of the cohort was 42 years (range 15-79 years). Eight patients had WHO Grade Ⅰ meningioma, and 9 had WHO Grade Ⅱ meningioma, respectively. Nine patients had clinical (radiological) diagnosis without histology. Seven patients received post-surgical PBRT (2 patients underwent Simpson Ⅰ-Ⅲ resection, 5 patients underwent Simpson Ⅳ-Ⅴ resection); 10 patients were irradiated for local recurrence after initial surgical resection. Results:All patients completed planned PBRT without break, and the median dose was 54 Gray-Equivalent (GyE) (range 50.4-60 GyE, 1.8-2 GyE/daily fraction). With a median follow-up of 22.2 (range 1.6-36.4) months, the 2-year overall survival and progression-free survival rates were both 100%. Grade Ⅰ skin erythema and alopecia were observed in 22 patients and Grade Ⅰ mucositis was observed in 2 patients. No acute of late toxicities of Grade 2 or above was observed.Conclusions:PBRT appeared to be a favorable treatment option for intracranial and skull base meningioma. Treatment-induced adverse effects and early response to PBRT were both highly acceptable. Longer follow-up is needed to evaluate the long-term outcome in terms of disease control, survival, as well as potential late effects.

Objective To evaluate the short-term efficacy and toxicities of intensity-modulated carbon ion radiotherapy (IMCT) for patients with locoregionally recurrent nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT).Methods A total of 112 patients with locoregionally recurrent nasopharyngeal carcinoma undergoing salvaging IMCT between May 2015 and February 2018were enrolled in the study.All patients previously received one course of definitive X-ray IMRT.Among them,10 patients (9％) were diagnosed with stage Ⅰ,26 patients (23％) with stage Ⅱ,41 patients (37％) with stage Ⅲ and 35 patients (31％) with stage Ⅳnasopharyngeal carcinoma,respectively.The median age of the cohort was 48 years (range,17-70 years) old.The median dose to the gross tumor volume (GTV) was 60 GyE (range,50-69 GyE).Results With a median follow-up time of 20 months (range,5-45 months),20 patients died and 42 patients developed local recurrence.The 2-year overall survival (OS) and local progression-free survival (LPFS) rates were 85％ and 52％.Both univariate and multivariate analyses demonstrated that stage Ⅳ disease was associated with significantly worse OS.No predictors were found for LPFS.No acute toxicity of grade 3 or higher was observed during reirradiation.Severe (grade 3 or above) late toxicities included xerostomia (n =1),hearing impairment (n =2),temporal lobe injury (n =1) and mucosal necrosis (n =19).Conclusions IMCT is an efficacious and safe treatment for patients with locoregionally recurrent nasopharyngeal carcinoma with acceptable toxicity profile.Long-term follow-up is necessary to further evaluate the long-term efficacy and late toxicities.

Objective To analyze the survival and toxicity after concurrent chemoradiotherapy in patients of different ages with stage Ⅳ non-small cell lung cancer (NSCLC).Methods Clinical data of 282 NSCLC patients in two prospective studies were retrospectively analyzed,who completed the protocol (at least 2 cycles of chemotherapy and thoracic radiation doses of ≥36 Gy).Among them,44 patients were assigned into in the young group (≤ 45 years old),161 patients in the middle-age group (46-64 years old) and 77 patients in the elderly group (≥ 65 years old).The clinical characteristics of patients among different groups were analyzed by x2 test.The overall survival (OS) was calculated by Kaplan-Meier method.Stratified analysis was performed by Log-rank test.Multi-factor prognosis analysis was conducted by Cox's proportional hazards regression model.Results The incidence of NSCLC in the male patients in the elderly group was higher than that in the middle-age and young groups.The 1-,2-,3-and 5-year OS did not significantly differ among different groups (P=0.810).The OS did not significantly differ among patients of the same gender,pathological type,T stage,N stage,metastasis status,same chemotherapy cycle,primary tumor dose and comprehensive treatment and short-term response (all P＞0.05).The incidence of adverse events did not considerably differ among different groups.Multivariate analysis demonstrated that age was not an independent factor for survival (P＞ O.05).Conclusion Patients of different ages with stage Ⅳ NSCLC obtain similar survival benefits and adverse events after concurrent chemoradiotherapy.

Objective: To evaluate the dosimetric difference between carbon ion radiotherapy and photon radiotherapy for treating tumors at lacrimal system. Methods: Using the CT images of 10 patients with tumors at lacrimal system, the carbon ion plan, the photon volume intensity modulation plan (VMAT) and the fixed wild photon intensity modulation radiotherapy (IMRT) plan were generated. The prescription was 54 Gy(RBE) in 18 fractions for clinical target volume (CTV) and 63 Gy(RBE) in 18 fractions for CTV-boost. Dosimetric differences of organ at risks were compared based on the same planning target volumes (PTVs) with similar dose coverages. Results: There was no statistically significant difference in the PTV coverage among three plans (P>0.05). Compared to VMAT and IMRT plans, carbon ion plans reduced the mean doses of eyeballs, mean doses and near-maximum doses of optical nerves of both ipsilateral ( t=7.35, 3.79, 4.66, 8.48, 2.52, 2.76, P<0.05) and contralateral eyes (t=3.87, 10.49, 9.16, 4.43, 6.53, 5.12, P<0.05), while the mean dose of brain was decreased from(5.65±3.58) and (5.76±2.09)Gy(RBE) to (0.81±0.90)Gy(RBE) (t=6.76, 17.33, P<0.05). Conclusions Compared to photon VMAT or IMRT, carbon ion could reduce the doses to optical critical organs around tumors. Thus, carbon ion radiotherapy has potential to reduce patients′ radiation related side-effects.