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BACKGROUND: Polymorphism of CYP3A5 gene can significantly affect the blood concentration of tacrolimus in the early period after kidney transplantation. Many studies in China are limited to the early 3 months after kidney transplantation with no concern on the long-term effect of tacrolimus in recipients. OBJECTIVE: To investigate the relationship between the polymorphism of CYP3A5 gene and tacrolimus concentration/dose (C0/D) in kidney transplant recipients, and to compare the differences among different genotypes, so as to provide an individualized drug regimen of tacrolimus after kidney transplantation. METHODS: Sixty-five adult recipients who underwent kidney transplantation and postoperative administration of tacrolimus (FK506) + mycophenolate mofetil (MMF) + prednisone (Pred) immunosuppressive therapy were divided into three groups according to their CYP3A5 genotypes detected preoperatively: CYP3A5*1/*1, *1/*3, and *3/*3 groups. The whole blood concentration of tacrolimus was monitored in all the recipients, and C0/D value was recorded in each group at different time points after surgery. The study protocol was in line with the ethical requirements of Air Force Hospital of Northern Theater Command. RESULTS AND CONCLUSION: There were 6, 25 and 34 recipients of CYP3A5*1/*1, *1/*3 and *3/*3, respectively. The C0/D value of tacrolimus in the CYP3A5*1/*1 and *1/*3 groups was significantly lower than that in the CYP3A5*3/*3 group (P < 0.05). At 7 and 14 days after surgery, the C0/D value of tacrolimus in the CYP3A5*1/*1 group was lower than that in the CYP3A5*1/*3 group (P=0.028, P=0.034). In the CYP3A5*1/*1 group, the C0/D value of tacrolimus at 7 days after surgery was significantly lower than that at 6 months and 1 year after surgery (P=0.35, P=0.41). In the CYP3A5*1/*3 group, the C0/ D value of tacrolimus at 7 days after surgery was significantly lower than that at 3 months, 6 months and 1 year after surgery (P=0.029, P=0.07, P < 0.01), and that at 14 days and 1 month after surgery was significantly lower than that at 6 months and 1 year after surgery (P=0.04, P=0.39). In the CYP3A5*3/*3 group, the C0/D value of tacrolimus at 7 days after surgery was significantly lower than that at 3 months, 6 months and 1 year after surgery (P=0.029, P=0.03), and that at 14 days after surgery was significantly lower than that at 6 months and 1 year after surgery (P=0.022). Overall findings indicate that the polymorphism of CYP3A5 gene has a significant effect on the C0/D value of tacrolimus in kidney transplant recipients, which can be maintained for a long-term stable period after transplantation. For CYP3A5*1/*1 and *1/*3 recipients, the metabolism of tacrolimus is faster in the early stage, and the dosage of tacrolimus should be increased to maintain the target blood concentration, whereas for CYP3A5*1/*3 recipients, the dosage of tacrolimus may be moderately less than the former and the drug reduction rate should be slowed down in the later stage. CYP3A5*3/*3 recipients have a slow metabolism of tacrolimus, and should be given a small dose in the early stage, and the reduction rate should be accelerated in the later stage.
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BACKGROUND: Currently, the researches on knee plaster immobilization paralysis animal models are popular in the world, but there are some insufficiencies with the knee paralysis animals, for example, poor animal selection, inappropriate plaster selection and pure gypsum instability, which affect the subsequent results. OBJECTIVE: To establish a rabbit model of knee paralysis by the knee fixation with plaster casts and wire. METHODS: A total of 20 New Zealand white rabbits were randomly divided into two groups. Models of right knee paralysis were established and fixed by plaster casts and wire. Normal controls were considered as the control group. At 8 weeks after fixation, right knee and pathologic histology were observed in the right knee. RESULTS AND CONCLUSION: The knee joints were translucent, smooth, and shiny, without the cartilage defect in the control group, and the cartilaginous elasticity and rigidity were good, and the arrangement of chondrocytes was normal. There were no inflammatory infiltrations in the articular capsule of the normal rabbits. In the model group, the knee joint was matt and opaque. Articular cartilage became thin, and showed poor elasticity. The cartilages were degenerated. Articular surface was rough, and had defects. There were smal amount of joint fluid or no joint fluid. Cartilage cel s shrank or disappeared, and the number of cartilage cel s reduced with degeneration and necrosis. Subchondral bone became sclerosis with trabecular bone of hyperplasia. The arrangement of cartilage cel s was disordered, with hyalinization and synovial vil ous hypertrophy. Cel clustering phenomenon was seen. There were a large number of lymphocytes, plasma cel s and neutrophil infiltration in cartilages. The typical pathological changes of the knee paralysis present in the rabbit cartilage. These results demonstrate that the rabbit model of knee paralysis can be successful y established by using fixation method with plaster casts and wire, which has the advantages of simple operation, strong fixation and no injury.
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BACKGROUND:The living standard of farmers and herdsmen in Xinjiang Uygur Autonomous Region, China is significantly lower than that of urban residents in general. Meanwhile, the shortage of doctors and medicines and lack of medical knowledge are the main reasons for local farmers and herdsmen to suffer from knee osteoarthritis. Most of the farmers and herdsmen are not aware of or prevent knee osteoarthritis in the early days to remove pathogenic factors, which results in a serious condition at the time of their medical treatment. OBJECTIVE: To investigate the main pathogenic factors of knee osteoarthritis in Uygur, Kazakh and Han populations in pastoral areas of northern Xinjiang Uygur Autonomous Region, China.METHODS:The permanent residents of Uygur, Kazakh and Han ethnic groups in northern Xinjiang, China who met the criteria were selected by the method of stratified, multistage and cluster random sampling during June 2012 to October 2014. The investigation of knee osteoarthritis was conducted among al the residents who meet the inclusion criteria using the method of home scene closed questionnaire. X-ray lateral plain film examination of the knee joint was performed among the patients presenting with the symptoms of knee osteoarthritis. The database was established. The multi-factor and unconditional Logistic regression analysis was conducted among the 40 variables using SPSS 20.0 software. RESULTS AND CONCLUSION:The 3 402 of 3 540 questionnaires were valid. The Logistic regression analysis suggest that the common pathogenic factors in Han, Uygur and Kazakh ethnic groups are associated with older ages, female gender, high body mass and drink alcohol. Smoking, history of internal disease, high education level, standing position, climbing, trauma, family history, fried food, housing conditions and amenorrhea, different nationalities, churchgoing of ethnic minorities are also the major risk factors. Among the three ethnic groups, the prevalence of female patients in Uygur and Kazak ethnic groups is significantly higher than that of Chinese Han nationality. The morbidity is different among these three nationalities. The dietary preferences cannot be determined as the related influencing factor of knee osteoarthritis. Whether the means of transportation, residence climate and environment, the number of pregnancies and deliveries, drinking tea or not, the type of tea are related to knee osteoarthritis remains unclear.
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AIM: To study the alterations of heme oxygenase-1 mRNA in vascular smooth muscle cells(VSMC) induced by lipopolysaccharide(LPS) and the role of heme oxygenase(HO)/carbon monoxide(CO)pathway in the disorders of regulation of cardiovascular system by LPS. METHODS: LPS (final concentrations 10 mg/L,30 mg/L and 50 mg/L) was added in cultured VSMCs for 6 h respectively or 10 mg/L LPS for 9 h and 18 h. MDA content, LDH release and the rate of trypan blue uptake of VSMC were measured. HO-1 mRNA expression was examined by Northern Blot. RESULTS: VSMC HO-1 mRNA expression was increased gradually with the increasing of LPS concentration. When final concentration of LPS was 50 mg/L, the HO-1 mRNA expression of VSMC was increased by 176.7% compared with control. When LPS final concentration was 10 mg/L, the HO-1 mRNA expression increased gradually along with the culture time. When cultured for 18 h, the HO-1 mRNA expression of VSMC was increased by 195.6% compared with control. Only at LPS 50 mg/L for 6 h and 10 mg/L for 18 h, the rate of trypan blue uptake，MDA content and LDH release were significantly increased. CONCLUSION: LPS can induce the HO-1 mRNA expression of VSMC and that were dose-dependent and time-dependent. The inducible HO may play an important role in the pathogenesis of vascular system under LPS.
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AIM: To investigate the influence of ischemic preconditioning on heart function, the activities of lactate dehydrogenase(LDH), malondialdehyde(MDA), and heme oxygenase-1(HO-1) after ischemia/reperfusion in isolated rat heart. METHODS: The model of Langendorff was used in isolated rat heart perfusion. Ischemic preconditioning protocol: stopping perfusion for 5 minutes and reperfusion for 5 minutes, repeating three times. Ischemia protocol: stopping perfusion for 40 minutes and reperfusion for 20 minutes. Indexes of heart function were recorded in control group, ischemia and reperfusion group(IR), and ischemic preconditioning group(IPC). The content of LDH of coronary effluent was measured. Moreover, the content of MDA and activity of HO-1 in myocardium were also measured. RESULTS: The recovery percentage of heart function in IPC group was significantly higher than that in IR group(P
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AIM: To study the alterations of heme oxygenase-1 mRNA in vascular smooth muscle cells(VSMC) induced by lipopolysaccharide(LPS) and the role of heme oxygenase(HO)/carbon monoxide(CO)pathway in the disorders of regulation of cardiovascular system by LPS. METHODS: LPS (final concentrations 10 mg/L,30 mg/L and 50 mg/L) was added in cultured VSMCs for 6 h respectively or 10 mg/L LPS for 9 h and 18 h. MDA content, LDH release and the rate of trypan blue uptake of VSMC were measured. HO-1 mRNA expression was examined by Northern Blot. RESULTS: VSMC HO-1 mRNA expression was increased gradually with the increasing of LPS concentration. When final concentration of LPS was 50 mg/L, the HO-1 mRNA expression of VSMC was increased by 176.7% compared with control. When LPS final concentration was 10 mg/L, the HO-1 mRNA expression increased gradually along with the culture time. When cultured for 18 h, the HO-1 mRNA expression of VSMC was increased by 195.6% compared with control. Only at LPS 50 mg/L for 6 h and 10 mg/L for 18 h, the rate of trypan blue uptake,MDA content and LDH release were significantly increased. CONCLUSION: LPS can induce the HO-1 mRNA expression of VSMC and that were dose-dependent and time-dependent. The inducible HO may play an important role in the pathogenesis of vascular system under LPS. [
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AIM: To investigate the effect of heme oxygenase /carbon monoxide(HO/CO) system on the pathogenesis of hypertension and effect of Heme-L- Lysinate(HLL), Zine protoporphyrin-IX(ZnPPIX) on vascular tension in a two kidney one-clip model. METHODS: The changes in mean arterial pressure and heart rate as well as phenylephrine(PHE)-induced contraction in isolated aortic rings of HLL, ZnPPIX- treated rats were examined after intraperitoneal administration of HLL and carbon monoxide( CO). RESULTS: (1) Injection of exogenous CO resulted in a significant decrease in mean arterial pressure in Sham and 2K1C groups(P