Objective To investigate the protective effects of antitumor necrosis factor-α antibody （TNF-αAb） on lung injury after cardiopulmonary bypass （CPB） and their mechanisms. Methods Forty healthy New Zealand white rabbits，weighting 2.0-2.5 kg，male or female，were randomly divided into 4 groups with 10 rabbits in each group. In groupⅠ，the rabbits received CPB and pulmonary arterial perfusion. In group Ⅱ，the rabbits received CPB and pulmonary arterial perfusion with TNF-αAb. In group Ⅲ，the rabbits received CPB only. In group Ⅳ，the rabbits only received sham surgery. Neutrophils count，TNF-α and malondialdehyde （MDA） concentrations of the blood samples from the left and right atrium as well as oxygenation index were examined before and after CPB in the 4 groups. Pathological and ultrastructural changes of the lung tissues were observed under light and electron microscopes. Lung water content，TNF-α mRNA and apoptoticindex of the lung tissues were measured at different time points. Results Compared with group Ⅳ，after CPB，the rabbitsin group Ⅰ to group Ⅲ showed significantly higher blood levels of neutrophils count，TNF-α and MDA（P＜0.05），higherTNF-α mRNA expression，apoptosis index and water content of the lung tissues （P＜0.05），and significantly lower oxyg-enation index （P＜0.05） as well as considerable pathomorphological changes in the lung tissues. Compared with group Ⅱ，after CPB，the rabbits in groups Ⅰ and Ⅲ had significantly higher blood concentrations of TNF-α （5 minutes after aortic declamping，220.43±16.44 pg/ml vs.185.27±11.78 pg/ml，P＜0.05；249.99±14.09 pg/ml vs.185.27±11.78 pg/ml，P＜0.05），significantly higher apoptosis index （at the time of CPB termination，60.7‰±13.09‰ vs. 37.9‰±7.78‰，P＜0.05；59.6‰±7.74‰ vs. 37.9‰±7.78‰，P＜0.05），significantly higher blood levels of neutrophils count and MDA （P＜0.05），significantly higher TNF-α mRNA expression and water content of the lung tissues （P＜0.05），and significantly loweroxygenation index （P＜0.05） as well as considerable pathomorphological changes in the lung tissues. Compared with groupⅠ，rabbits in group Ⅲ had significantly higher above parameters （P＜0.05） but lower oxygenation index （P＜0.05） only at 30 minutes after the start of CPB. Conclusion Pulmonary artery perfusion with TNF-αAb can significantly attenuate inflammatory lung injury and apoptosis of the lung tissues during CPB.
The damage effects of the pure tumor necrosis factor (TNF) on the normal animals were observed. Eighteeen rabbits were divided into two groups, eight in tested group and ten in control group. 0.5mg per kg of the pure rabbit TNF was given to each animal of the tested group. Results:The symptoms similar to that induced by endotoxin appeared after the TNF injection. The functions of the main organs were markedly damaged. The arterial blood pressure of most animal was low. The weight ratio of the orgen to the body was raised. The pathologic changes were similar to those of the multiple organ failure (MOF) model. Most of the animal died before the end of the experiment. The results suggest that pure TNF could indece multiple organ damages similar to those of MOF.
Objective To explore a new method of treating early avascular necrosis of femoral head (AVNFH). Methods Sixty-nine New Zealand adult rabbitswith a mean weight of 2.8 kg after AVNFH presenting were randomly divided into three groups. In group A, deproteinized bone(DPB) combined with the recombinant plasmid pcDNA3.1/vascular endothelial growth factor 165(VEGF165) was implanted in the drilled channel of the necrotic femoral head. In group B, only DPB was implanted. In group C, channel was drilled without DPB or plasmid implanted. Femoral head specimens were obtained 3 days, 1, 2, 4, 8 and 16 weeks after operation. The expression of VEGF165 was examined by RT-PCR, Western blot and immunohistochemical techniques. X-ray testedbone formation generally. Angiogenesis and repair of the femoral head were observed by histological and histomorphometric analysis. Results In group A, the expressions of VEGF165 mRNA and protein were detected 3 days postoperatively, reached apex 1 week and lasted more than 3 weeks after implantation. The ratios of IOD of collagen type Ⅰ were 0.29±0.11, 0.55±0.13 and 0.67±0.10 IOD/μm2 respectively at 2, 4 and 8 weeks postoperatively and the ratios of IOD of new capillary vessels were 0.33±0.10and 0.57±0.16 IOD/μm2 respectively at 2, 4 weeks postoperatively in group A, showing statistically significant difference (Plt;0.01) when compared with groups B and D. X-ray test indicated much bone callus formed early. Conclusion Transfection of the VEGF165 gene can enhance local angiogenesis at early stage andDPBVEGF165 compound can improve bone formation. Deproteinized bone combined with VEGF165 gene provides a potential method for therapy of osteonecrosis.
Objective To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure. Methods Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described. ResultsThe age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences (P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group. Conclusion The incidence of ONFH after GC exposure in China’s SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.
Objective To study the mechanism of compound of calcium phosphate(TCP) and platelet-rich plasma(PRP) in the treatment of femoral head necrosis.Methods The left femoral heads of 48 New Zealand white rabbits were frozen by liquid nitrogen as to make themodel of femoral head necrosis.Twenty-four rabbits were randomly chosen as theexperimental group and their femoral heads were filled with TCP/PRP. The other 24 rabbits were used as the control group and their femoral heads were filled only with TCP. They were sacrificed at 2, 4,8,12 weeks after operation. The specimens were examined with X-ray and histological study.Results At 2 weeks after operation,there was no significant difference in femoral headdensity between the two groups. Four weeks after operation, femoral head density decreased in both groups, while it decreased more in the control group. At 8,12 weeks after operation, the density of the femoral heads in both groups increased, and it was higher in the experimental group. Histology examination showed thatthere was no difference between the two groups 2 weeks after operation. The head became flat at 4 weeks. Control group had more defects. At 4,8,12 weeks, more repairs were observed in the experimental group than that in the control group. The amount and maturity of osteogenesis in experimental group were much more greaterthan those in control group．Bone histomorphometry showed that the volum of thetrabecular was larger in the experimental group (36.65%±7.22%,38.29%±4.28%，39.24%±3.42%) than that of control group(P＜0.05). Conclusion TCP/PRP does not only provide osteoblasts scaffold, butalso promotes bone formation and the head repair. TCP/PRP is a good biomaterialfor the treatment of femur head necrosis.
In order to study the curative effect of vascularized bone graft in the treatment of avascular necrosis of talus, 24 patients were treated with vascularized bone grafts, in which 9 cases had received 1st cuneiform bone graft with a malleolaris anteriomedialis, 4 cases with the 1st cuneiform bone graft with the medial tarsal artery and 11 cases with vascularized cuboid bone graft with the lateral tarsal artery. All of the patients were followed up for 3-5.5 years. The clinical observation and X-ray examination showed that function of the ankle joint was completely or almost normal in 16 cases, and the bone repair was excellent. There was slight pain in the ankle joint in 4 cases. The efficiency rate of the treatment was 83.3%. It could be concluded that vascularized bone graft might be an effective method in the treatment of avascular necrosis of talus.
Descending necrotizing mediastinitis （DNM）is a severe infection spreading from the cervical or odontoiatric region to the mediastinum through the anatomic cervical spaces. DNM is very rare but fatal. The course of the illness proceeds rapidly and the mortality rate is high. The pathogenic process is closely related to anatomical and physiological characteristic of cervix and mediastinum. The most valuable way for decreasing its high mortality rate is to give early diagnosis and treatments. Computed tomography(CT) scan is especially important method in early diagnosis.The early and enough use of broad spectrum antibiotics, individual surgical management based on neck and chest CT, such as clearing necrotic tissues,drainage and flushing are all effective methods to decrease mortality rate. Related management , such as department of stomatology, head and neck surgery, thoracic surgery,intensive care unit, and infectious department,should give cooperative therapy when necessary. At the same time, more attention should be paid to the patients who have some systemic disease such as diabetes mellitus and whose physical constitutions are very poor, which could lead to DNM and worsening. It can help to decrease the incidence rate of fatal complications and to increase cure rate.
Objective To investigate the effects of expression of TNFα mRNA on glucose uptake in both the liver and skeletal muscle after endotoxemia. Methods In the mice with intraperitoneal injection of lipopolysaccharide (LPS), the changes of TNFα level of plasma and uptake of 2-deoxyglucose (2-DG) in the isolated soleus muscle and hepatic tissues were determined, then the reinstatement of glucose uptake by injecting TNF-McAb for 3 days was also observed. In addition, changes of TNFα mRNA expression of liver were evaluated. Results The expression of TNFα mRNA in the liver showed markedly increased in the first 3 hours post endotoxemia and remaind high for 3 days, and the plasma TNFα level paralleled with TNFα mRNA expression of liver also was elevated. The basal uptake of 2-DG both in muscle and liver were markedly increased, but the stimulated 2-DG uptake with insulin was greatly reduced as compared with the control. In addition, these abnormalities of 2-DG uptake can be partially corrected by neutralization of the circulatory TNFα by administration of TNF-McAb. Conclusion The disorders of glucose uptake of the liver and the muscle due to the overexpression of TNFα mRNA and elevated circulatory TNFα level may be the mechanism of insulin resistance after endotoxemia.