ObjectiveTo study the possbility of using intranasal instillation of fine particulate matter (PM2.5) combined with inhalation of ozone (O3) to establish mouse model of combined pulmonary fibrosis and emphysema (CPFE), and to provide a reference for the establishment of CPFE model.MethodsMale C57/BL6 mice were divided randomly into phosphate buffer saline (PBS) intranasal instillation+air inhalation group, PBS intranasal instillation+O3 inhalation group and PM2.5 intranasal instillation+O3 inhalation group, with 8 mice in each group. The mice were intranasally instilled with PBS or PM2.5 suspension (7.8 mg/kg) followed by air or ozone inhalation 24 hours later, twice a week over 8 weeks. Lung function, bronchoalveolar lavage fluid (BALF) cell counts and classification were detected, the pathological changes of lung tissues in hematoxylin-eosin staining were observed, including inflammation scores and mean linear intercept (Lm). The thickness of collagen deposition in subepithelium was measured in lung tissues in Masson staining, and simultaneously hydroxyproline contents in lung tissues were determined.ResultsCompared to PBS instillation+air inhalation group, inspiratory capacity (IC), total lung capacity (TLC) and chord compliance (Cchord) were increased, FEV25 (the forced expiratory volume at 25 ms)/FVC (forced vital capacity) was decreased, total cell counts in BALF, Lm and lung inflammatory scores were increased, the thickness of the subepithelial collagen layer (SEc/Pbm) or hydroxyproline contents was not changed in PBS instillation +O3 inhalation group; IC was decreased, functional residual capacity (FRC) was increased, TLC was increased, Cchord was decreased, FEV25/FVC and FEV50 (the forced expiratory volume at 50 ms)/FVC were decreased, total cell counts in BALF, Lm, lung inflammatory scores, SEc/Pbm and hydroxyproline contents were increased in PM2.5 instillation+O3 inhalation group. Compared to PBS instillation+O3 inhalation group, IC was decreased, FRC was increased, Cchord was decreased, FEV25/FVC and FEV50/FVC were decreased, total cell counts in BALF, Lm, lung inflammatory scores, SEc/Pbm and hydroxyproline contents were increased in PM2.5 instillation +O3 inhalation group.ConclusionCPFE mouse model can be successfully established by PM2.5 intranasal instillation combined with ozone inhalation for consecutive 8 weeks.
Objective To establish the model of pancreatoduodenal allotransplantation in pigs with enteric drainage (ED) and portal venous drainage (PVD). Methods Forty-six hybrid landraces were divided into two groups (donor and recipient groups) randomly, for pancreatoduodenal allotransplantation. Donors were perfused via abdomial aorta without clamping the portal venous outflow with UW solution after heparinization. Whole pancreatoduodenal graft was arvested with segments of abdomial aorta and portal vein and shaped under cold UW solution. Then, the end-to-end nastomosis was performed with the donor iliac artery bifurcation “Y” graft to the recipient superior mesenteric arteries and celiac artery. Furthermore, type Ⅰdiabete model was made by removal of the recipient pancreas. The venous anastomosis was reconstructed between the donor portal vein and the recipient superior mesenteric vein. Meanwhile, the end-to-side anastomosis was performed with the donor common iliac artery bifurcation “Y” graft to the recipient abdomial aorta and the side-to-side intestinal anastomosis was performed between the donor duodenum and the recipient jejunum. External jugular vein was intubated for transfusion. The levels of blood glucose， insulin and glucagon in blood were measured before and during the operation and 1， 3， 5， 7 d after operation. Results Twenty-three cases of pancreatoduodenal allotranplantations were performed on pigs. One died from complication of anesthesia. Success rate of operation was 95.7％.Complications of operation happened in 2 cases in which one was phlebothrombosis, incidence 4.5％and the other was duodenojejunal anastomotic leak, incidence 4.5％. The level of blood glucose increased within 30 min and recovered on the 2nd day after removal of pancreas. The levels of insulin and glucagon decreased within 30 min and recovered on the 2nd day after removal of pancreas. Rejection curred at the 1st day and reached the worst level on the 9th day after transplantation without the change of insulin and glucagon in blood and clinical symptoms of rejection. Conclusion Pancreatoduodenal transplantation in pigs can treat type Ⅰ diabete. ED and PVD can keep the function of endocrine in normal. The technique of duodenal transplantation with ED and PVD may pave the way for the further development of pancreas transplantation in clinic.
ObjectiveTo observe the pathological changes in heart and lung tissues in rats with pulmonary hypertension induced by monocrotaline. MethodsTwenty-four male Sprague-Dawley rats were randomly and equally divided into an experimental group and a control group. The rats in the experimental group were intraperitoneally injected with monocrotaline to induce pulmonary hypertension, and the rats in the control group were treated with saline. All rats were fed for 3 weeks, and the general situation were observed. Then the rats were sacrificed for measurement of mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index [RV/(LV+S)], changes of myocardial cells and lung vascular, calculated density of middle membrane smooth muscle cells (SMC) in medium/small pulmonary arteries accompanied with bronchi and alveoli, media thickness of pulmonary artery (PAMT), the percentage of wall thickness with outer diameter (WT%), the percentage of wall area with total area (WA%), the average diameter of myocardial cells (AD), and myocardial nuclei density (MND). ResultsCompared with the control group, the condition of rats in the experimental group were getting worse obviously.mPAP and RV/(LV+S) were both increased (both P < 0.05). The observation by light microscope revealed that obvious myocardial hypertrophy and structure disturbances, severe luminal stenosis of medium/small pulmonary arteries, medial thickening, infiltration of inflammatory cell in tissue space, proliferation of unorganized collagen fibers in the experimental group. The observation by electronic microscope showed proliferation of endothelial cell with irregular nuclei, increased organelles and vacuoles in the experimental group. The differences in SMC, PAMT, WT%, WA%, AD, and MND were significant between two groups (all P < 0.05). ConclusionsThe monocrotaline can induced pulmonary hypertension and right ventricular hypertrophy. The mechanism may be related to severe stenosis or occlusion of the vessel lumen caused by plexiform proliferation of endothelial cells, proliferation of smooth muscle cells and collagen fibers, compensatory hypertrophy and hyperplasia of myocardial cells.
ObjectiveTo study the feasibility and advantages of preparing an animal model of defecation reconstruction after spinal cord injury in rats by mechanical polishing method. MethodsForty adult female Sprague Dawley rats (weighing, 250-300 g) were randomly divided into 2 groups (n=20). The lamina was opened by mechanical polishing method to expose the cauda equina in experimental group, then bilateral L5 and S1 nerve roots end-to-end anastomosis was done under 10 times microscope, and finally cauda equina between the L5 and L6 (except S1) was cut. The lamina was opened by traditional bites method in control group, and the other treatment methods were in agreement with the experimental group. The operative time, intra-operative blood loss, and situation of rats at postoperative 3 days were recorded. ResultsThe operative time of experimental group[(93.05±7.60) minutes] was significantly shorter than that in control group[(131.30±11.68) minutes] (t=12.279, P=0.000); intra-operative blood loss in experimental group[(4.33±0.46) mL] was significantly lower than that in control group[(7.36±0.58) mL] (t=18.293, P=0.000). At 3 days after operation, 18 rats (90%) survived in experimental group, and 12 rats (60%) survived in control group; difference was significant in the survival rate between 2 groups (χ2=4.800, P=0.028). ConclusionTo establish an animal model of defecation reconstruction after spinal cord injury in rats by mechanical polishing method is feasible, and it has shorter operative time, less blood loss, and lower postoperative mortality than the traditional bites method. But there is a certain learning curve and requirement to master microsurgical techniques.
Retinal ischemia is the common pathologic process in many ophthalmic diseases, including ischemic optic neuropathy, retinal artery and vein occlusion, carotid artery obstructive disease, retinopathy of prematurity, chronic diabetic retinopathy and glaucoma. It is very important to establish animal models to investigate pathology mechanism and explore the treatment of retinal ischemia disease. At present, the commonly used methods for establishing retinal ischemia animal models include increasing intraocular pressure, ligating of blood vessels, suture method, photochemical method, and drug injection etc. This article summarizes the methods to establish the animal models and analyzes the indication for each animal model. It is expected that the method of establishing a retinal ischemic animal model will be helpful to the experimental design of follow-up retinal ischemia studies.
Objective To systematically review the pharmacoeconomic evaluation related to relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), and to summarize its model structure, parameter inclusion and other methodological parts for future r/r B-ALL-related interventions, and to provide references for conducting pharmacoeconomic evaluations. Methods PubMed, EMbase, The Cochrane Library, CNKI and WanFang Data databases were electronically searched to collect relevant literature on the pharmacoeconomic evaluation model of r/r B-ALL from inception to August 6th, 2021. Two reviewers independently screened literature, extracted data, and assessed the quality of the included studies. The data on the model structure, methods, and parameter inclusion were then summarized. Results A total of 10 studies using different modeling methods were included. Due to the lack of head-to-head trials, most of the efficacy parameters for the intervention and control groups were derived from different clinical trials and compared indirectly. All studies used quality-adjusted life years (QALYs) as output indicators, and some used life years (LYs) as output indicators and reported the incremental cost effectiveness ratio (ICER). All studies measured the cost of treatment and hematopoietic stem cell transplantation; a few studies also conducted subgroup analysis. Conclusion The number of studies on the economic evaluation of r/r B-ALL is relatively small, and there are large differences in model types, health status, and parameter inclusion. It is suggested that researchers should guarantee the integrity of the report format and normative according to available data choice drug economics evaluation model and establish the reasonable hypothesis under the condition of the patient population heterogeneity uncertainty, perform subgroup analysis especially on the subgroup which did not receive salvage therapy. In the absence of head-to-head clinical trials, appropriate indirect comparison methods are adopted according to the data obtained to reduce methodological differences and improve the quality of relevant pharmacoeconomic research in China.
ObjectiveTo explore the CT imaging features and independent risk factors for cystic pulmonary nodules and establish a malignant probability prediction model. Methods The patients with cystic pulmonary nodules admitted to the Department of Thoracic Surgery of the First People's Hospital of Neijiang from January 2017 to February 2022 were retrospectively enrolled. They were divided into a malignant group and a benign group according to the pathological results. The clinical data and preoperative chest CT imaging features of the two groups were collected, and the independent risk factors for malignant cystic pulmonary nodules were screened out by logistic regression analysis, so as to establish a prediction model for benign and malignant cystic pulmonary nodules. ResultsA total of 107 patients were enrolled. There were 76 patients in the malignant group, including 36 males and 40 females, with an average age of 59.65±11.74 years. There were 31 patients in the benign group, including 16 males and 15 females, with an average age of 58.96±13.91 years. Multivariate logistic analysis showed that the special CT imaging features such as cystic wall nodules [OR=3.538, 95%CI (1.231, 10.164), P=0.019], short burrs [OR=4.106, 95%CI (1.454, 11.598), P=0.008], cystic wall morphology [OR=6.978, 95%CI (2.374, 20.505), P<0.001], and the number of cysts [OR=4.179, 95%CI (1.438, 12.146), P=0.009] were independent risk factors for cystic lung cancer. A prediction model was established: P=ex/(1+ex), X=–2.453+1.264×cystic wall nodules+1.412×short burrs+1.943×cystic wall morphology+1.430×the number of cysts. The area under the receiver operating charateristic curve was 0.830, the sensitivity was 82.9%, and the specificity was 74.2%. ConclusionCystic wall nodules, short burrs, cystic wall morphology, and the number of cysts are the independent risk factors for cystic lung cancer, and the established prediction model can be used as a screening method for cystic pulmonary nodules.