Recent studies showed that certain drugs can change regulatory reaction parameters in gene regulatory networks (GRNs) and therefore restore pathological cells to a normal state. A state control framework for regulating biological networks has been built based on attractors and bifurcation theory to analyze this phenomenon. However, the control signal is self-developed in this framework, of which the parameter perturbation method can only calculate the state transition time of cells with single control variable. Therefore, an optimal control method based on the dynamic optimization algorithms is proposed for complex biological networks modeled by nonlinear ordinary differential equations (ODEs). In this approach, dynamic optimization problems are constructed based on basic characteristics of the biological networks. Furthermore, using an example of a simple low-dimensional three-node GRN and a complex high-dimensional cancer GRN, MATLAB is utilized to calculate optimal control strategies with either single or multiple control variables. This method aims to achieve accurate and rapid state regulation for biological networks, which can provide a reference for experimental researches and medical treatment.

Objective To compare the prognosis of vascular in situ and bridge vessel percutaneous coronary intervention ( PCI) therapy strategies in patients with recurrent angina after coronary artery bypass grafting ( CABG) . Methods A total of one hundred and two patients with recurrent angina after CABG from January 2008 to January 2016 were involved in this study and were divided into two groups according to interventional therapy strategy:74 patients in the vascular in situ PCI group ( in situ group,74 cases) and 28 patients for bridge vessel PCI group ( bridge vessel group,28 cases) . The patients have been followed up for (33. 6± 10. 2) months. The major adverse cardiovascular events ( MACE) of the two groups were recorded, including non?fatal acute myocardial infarction ( AMI) ,target vessel revascularization ( TVR) and cardiac death, and multivariate logistic regression analysis was used to analyze the related factors of MACE. Results Compared with the bridge vessel group,the non?MACE survival rate,non?AMI survival rate and non?TVR survival rate of the in situ group were significantly increased ( ( 71. 6% ( 53/74 ) vs. 57. 1% ( 16/28 ) , 93. 2% ( 69/74 ) vs. 82. 1% (23/28),81. 1% (60/74) vs. 67. 9% (19/28) ),the differences were statistically significant (χ2=8. 141,4. 219,5. 436, P<0. 05) . Multivariable logistic regression analysis showed that age of bridge ( OR=1. 023,95%CI 1. 005-1. 026,P=0. 019) ,diabetes mellitus ( OR=2. 386,95%CI 1. 425-3. 991,P=0. 003) and bridge vessel PCI (OR=1. 884,95%CI 1. 093-3. 220,P=0. 025) were factors that affect the clinical prognosis in patients with recurrent angina pectoris after CABG. Conclusion The clinical prognosis of the in situ PCI is better than bridge vascular PCI in patients with recurrent angina after CABG,while the age of bridge, diabetes mellitus, vascular interventional treatment are factors for the effect of interventional therapy patients prognosis. The clinical prognosis is much better in native vessel PCI than that of bridge vessel PCI in patients with recurrent angina after CABG. The age of bridge,diabetes mellitus and bridge vessel PCI are the factors that affect the clinical prognosis in the patients.

Objective To compare the efficacy of native vessel percutaneous coronary intervention (NV-PCI) and optimal drug therapy (ODT) in patients with recurrent angina after coronary artery bypass grafting (CABG). Methods The clinical data of 142 recurrent angina pectoris after CABG patients who had underwent coronary angiography were retrospectively analyzed. Among the patients, 70 cases were treated with NV-PCI (NV-PCI group), and 72 cases were treated with ODT (ODT group). The incidence of major adverse coronary events (MACE) and left ventricular ejection fraction (LVEF) were compared between 2 groups. Results All patients were followed up for at least 1 years. There were no statistical differences in the number of bypass vessels and number of occluded vessels between ODT group and NV-PCI group: (2.5 ± 0.7) branches/case vs. (2.4 ± 0.9) branches/case and (1.4 ± 0.9) branches/case vs. (1.3 ± 0.7) branches/case, P>0.05. The incidence of MACE in NV-PCI group was significantly lower than that in ODT group: 12.9％ (9/70) vs. 22.2％ (16/72), and the LVEF was significantly higher than that in ODT group:(63.5 ± 14.0)％vs. (57.1 ± 9.0)％, and there were statistical differences (P<0.05). Conclusions Compared with the ODT, the NV-PCI has lower incidence of MACE and higher LVEF in patients with recurrent angina pectoris after CABG.

Objective:To explore the influence on inflammation cytokines for anti-IL-1βand TNF-αIgY intranasal treatment in guinea pigs with allergic rhinitis.Methods:The allergic rhinitis model in guinea pigs was established using ovalbumin(OVA).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-IL-1βand TNF-αIgY treatment group(group Z1,n=21)and the fluticasone propionate treatment group(group Z2,n=21). At 2 h,4 h and 8 h after the last treatment,blood was got by heart puncture,as well as nose was lavaged using 0.9% saline and the nasal lavage fluid( NLF) was collected.The level of cytokines was examined using ELISA kits.Results: In the peripheral blood, the levels of IL-1β,IL-5,IL-9,IL-13,IL-18,IL-33 and TGF-β1 from 2 h to 8 h;TNF-αand OVA-specific IgE from 2 h to 4 h;and IL-22 from 4 h to 8 h were significantly decreased in the 0.1%anti-IL-1βand TNF-αIgY treatment group compared with the allergic rhinitis model group(P<0.05).In the NLF,the levels of IL-1β,IL-5,IL-9,IL-13,IL-22,IL-33,TNF-α,TGF-β1 and OVA-specific IgE from 2 h to 8 h;and IL-18 at 2 h were significantly decreased in the 0.1% anti-IL-1βand TNF-αIgY treatment group compared with the allergic rhinitis model group ( P<0.05 ) .Conclusion: Anti-IL-1βand TNF-αIgY intranasal treatment can significantly reduce inflammation cytokine levels in allergic rhinitis guinea pigs.

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 the expression of Toll-like receptor 4 (TLR4),and explore its relationship with neurological function after fluid percussion brain injury in rats.Methods 56 adult rats were randomly divided into traumatic brain injury group(TBI group,n=48) and sham operation group(SO group,n=8).The experimental models were established.The water content of edematous brain and the expression of TLR4 were measured with dry-wet measure,immunohistochemistry and Western Blot at 1 h,6 h,12 h,24 h,3 d,7 d after shock respectively.Results Compared with SO group,neuronal function score decreased in TBI group from 6 h(3.86±0.42),reached to the lowest level at 24 h(2.65±0.32),and gradually rose at 3rd day (3.25±0.17).TLR4 immunoreactive expression increased from 6 h,reached its maxmum at 24 h,lasted to 3rd day,and then began to drop at 7th day.The linear regression analysis indicated that expression of TLR4 had negative correlation with change of neuronal function score (r 1 =-0.824,r w =-0.867,P＜0.05).Conclusion TLR4 expression is upregulated following fluid percussion injury in rats and involved in neurological function impairment by inducing secondary inflammatory brain injury.

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 .

BACKGROUND:It has been studied that the distribution of bone morphogenetic protein 2 is regular under bone defect situation. OBJECTIVE:To observe the expression of bone morphogenetic protein 2 in rabbit radial defect site with different lengths. METHODS:Forty-eight New Zealand rabbits were divided into two groups randomly, 0.5 cm bone defect and 3.0 cm bone defect were made by wire saw at the middle part of radius bone after anaesthesia. RESULTS AND CONCLUSION:Western blot results showed that in the 0.5 cm bone defect group, the expression of bone morphogenetic protein 2 of the tissues in the bone defect site was increased gradual y at 1, 3, 4 weeks after operation, and the expression in each defect group was increased when compared with that immediately after injury (P<0.05). In the 3.0 cm bone defect group, the expression of bone morphogenetic protein 2 of tissues in bone defect site was increased gradual y and reached to its peak at 3 weeks after the operation (P<0.05), and the peak value in the 3.0 cm bone defect group was significantly higher than that in 0.5 cm bone defect group (P<0.05). The peak value was maintained in high level. The comparison of bone cal us formation showed that the bone cal us formation of 3.0 cm bone defect group was less than that of the 0.5 cm bone defect group at 3 and 4 weeks after operation (P<0.05). The results indicate that expression of the bone morphogenetic protein 2 in 3.0 cm bone defect site is increased significantly, but the expression level cannot make the bone defect heal itself.

Objective To improve the rheumatologists' understanding of noncirrhotic portal hypertension.MethodsA case of systemic sclerosis complicated by noncirrhotic portal hypertension was reported and the related literatures were reviewed.Results A 51-year-old female who had been diagnosed as systemic sclerosis presented clinically with an chronic onset of portal hypertension.She also had pancytopenia,splenomegaly,and significant esophageal varices.Liver function tests were normal.Hepatitis viral serology was negative.Ultrasound scan of liver revealed no focal lesion.ACT scan confirmed the absence of portal vein thrombosis.Taking into account the above evaluation we concluded that the patient had systemic sclerosis and noncirrhotic portal hypertension.The patient was on prednisolone and immunosuppressant and the condition was well.Conclusion Noncirrhotic portal hypertension complicated by autoimmune disease,especially SSC,is very poor,characteriged by significant portal hypertension as well as histological evidence that cirrhosis is absent.Rheumatilogist should pay attention to it.

Objective:To investigate the mechanism of immunoglobulin Y antibodies(IgY) against tumour necrosis factor alpha(TNF-α) and Interleukin-1beta(IL-1β) in treating allergic bronchial asthma through nebulization inhalation.Methods:The allergic bronchial asthma model was established with Hartley guinea pig by ovalbumin nebulizating inhalation.The animals were randomly divided into 4 groups: normal control group(group A)，allergic bronchial asthma group(group B),0.1% anti-TNF-α and IL-1β IgY treating group(group C),1.0% anti-TNF-α and IL-1β IgY treating group (group D).The animals were killed after treatment being accomplished for 2 h,4 h,8 h,24 h and the lungs were made pathological,which were then stained by hematoxylin-eosin(H.E.).The bronchoalveolar lavage fluid (BALF) was collected and the deposited cells were stained by Wright's.Results:①The histological appearance of lung: In group B the histological structure of alveolar ducts and alveolar walls was damaged,the alveolar space was full of transudate and lots of alveolar epithelial cells and leucocytes.The pulmonary interstitial edema,inflammatory cells infiltration,distorted or dilated capillaries and reducing capillary numbers of effective blood stream were observed in alveolar walls.In group C and group D the damage degree of alveolar ducts and alveolar wall was slighter than that in group B and there were few inflammatory cells in alveolar space.In bronchial lumen and pulmonary alveoli the sticky mucus plug was obviously less in group C and group D than in group B.Moreover,inflammatory cell infiltration was seldom observed aroud bronchia,and restoration of bronchial tunica mucosa epithelium was obviously observed in group C and group D.②The cytology appearance of BALF: In group C and group D the numbers of eosinophils,neutrophils,lymphocytes were significantly fewer （2 h,4 h,8 h,P＜0.05）,however,the number of macrophage was significantly more（2 h,4 h,8 h,P＜0.05）than in group B.Conclusion:The anti-TNF-α and IL-1β IgY can obviously alleviate pathological extent of inflammatory reaction in allergic bronchial asthma of guinea pigs by nebulization inhalation therapy.The therapeutic effect of anti-TNF-α and IL-1β IgY between 0.1% and 1.0% concentration is not obvious difference for pathology changes.