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 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 .

The elastic parameters of soft tissues are important for medical diagnosis and virtual sur-gery simulation.In this study;we propose a novel nonlinear parameter estimation method for soft tissues.Firstly;an in-house data acquisition platform was used to obtain external forces and their corresponding deformation values.To provide highly precise data for estimating nonlinear param-eters;the measured forces were corrected using the constructed weighted combination forecasting model based on a support vector machine (WCFM_SVM). Secondly;a tetrahedral finite element parameter estimation model was established to describe the physical characteristics of soft tissues;using the substitution parameters of Young's modulus and Poisson's ratio to avoid solving compli-cated nonlinear problems.To improve the robustness of our model and avoid poor local minima;the initial parameters solved by a linear finite element model were introduced into the parameter estimation model. Finally;a self-adapting Levenberg–Marquardt (LM) algorithm was presented;which is capable of adaptively adjusting iterative parameters to solve the established parameter estimation model. The maximum absolute error of our WCFM_SVM model was less than 0.03 Newton;resulting in more accurate forces in comparison with other correction models tested. The maximum absolute error between the calculated and measured nodal displacements was less than 1.5 mm;demonstrating that our nonlinear parameters are precise.

Objective:To investigate the efficacy of internal fixation maintenance after fracture-related infection (FRI).Methods:Retrospectively analyzed were the data of 81 patients with deep FRI after 6 weeks of internal fixation who had been treated with hardware maintenance at Department of Orthopedics, The Second Hospital Affiliated to School of Medicine, Zhejiang University between 2013 and 2021. They were 61 males and 20 females, aged from 11 to 73 years (average, 11 years). After admission, the patients received bacterial culture, thorough debridement, negative pressure suction, soft tissue repair, and local and intravenous antibiotics. If a joint was affected by FRI, its cavity was cleaned and drained. Infection control and fracture healing were regularly observed in all patients. A treatment was considered successful when the internal fixation was maintained until fracture union, and considered as unsuccessful when the internal fixation was removed before fracture union. Risk factors associated with treatment failure were identified from gender, age, smoking, diabetes, fracture type, methicillin-resistant Staphylococcus aureus (MRSA) infection, methicillin-susceptible staphylococcus (MSSA) infection, Pseudomonas aeruginosa infection, Escherichia coli infection, infection by two kinds of bacteria, negative bacterial culture, early infection (within 2 weeks) and local use of antibiotics.Results:All patients were followed up for an average of 30 months (from 6 to 84 months). Fracture union was achieved in 62 (76.5%) patients with infection control and internal fixation retained. Masquelet technique was used to treat bone defects in 2 patients; a muscle flap or skin flap was used to reconstruct soft tissue coverage in 11 cases; fracture union was achieved by antibiotics and dressing changes in 2 patients with sinus tract. Amputation was performed in one unsuccessful case due to uncontrollable infection, and internal fixation was changed to external fixation in the other 18 unsuccessful cases, of which 3 achieved final bone union after application of Masquelet technique, 7 achieved final bone union after application of bone transfer technique, and 3 achieved soft tissue coverage after reconstruction with flap technique. Pseudomonas aeruginosa infection, open fractures and FRI for more than 2 weeks were high risk factors for failure in internal fixation maintenance ( P<0.05). Conclusions:If internal fixation is still stable and effective, hardware maintenance should be tried first in the patients with FRI within 6 weeks after fracture internal fixation. Muscle flap or skin flap surgery should be performed as soon as possible to effectively control infection and promote fracture union in the patients with soft tissue defects after thorough and effective debridement. History of open fracture, Pseudomonas aeruginosa infection, and FRI for over 2 weeks may be risk factors for failure in internal fixation maintenance.

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.