Objective To explore the mechanism of the femoral head necrosis induced with long term glucocorticoid treatment by means of microvascular density and cellular ultrastructure. Methods 40 Japanese rabbits were used to establish an animal model of the femoral head necrosis induced by long term glucocorticoid treatment using injection with methylprednisolone 8 mg/kg weekly. In studying cellular ultrastructure and microvascular density of the femoral head necrosis models, the slides were made after vascular infusion with Chinese ink on 4th, 8th, and 12th week of the experiment. The network of microvasculature of the rabbit ear was photographied as a reference data before and after methylprednisolone treatment. Results Microvascular density in bilateral cancellous and compact bone of the femoral head became decreased statistically after 12 weeks of glucocorticoid treatment(P

Objective To study the correlation between mutant selection window (MSW) and selective enrichment of Staphylococcus aureus resistant mutants in vivo. Methods Tuberculosis patients colonized with S. aureus in anterior nares were selected as experimental group. The susceptibility of S. aureus to rifampicin was determined at the beginning of and 2,4 and 5 weeks after the anti-tuberculosis therapy with rifampicin-containing regimens. S. aureus isolates developing acquired resistance were examined by molecular strain typing. Diabetes patients colonized with S. aureus served as an untreated control. Results The S. aureus isolated from 5 patients acquired rifampicin resistance in 58 tuberculosis patients. It was determined by pulsed-field gel electrophoresis and protein A repeat sequence the strains of S. aureus were different, but the isolates obtained from the same patient before and after acquisition of resistance were the same strains. No resistance was acquired in 39 untreated control patients, which differed statistically from treated patients. Conclusion The selective enrichment of rifampicin-resistant S. aureus mutants occurred when rifampicin concentration was in the mutant selection window.

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.

OBJECTIVE: To observe the effects of Kangfengshi Granules (KFSG) on expressions of the mRNAs of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) in bone tissues of rats with collagen-induced arthritis. METHODS: Forty SD rats were randomly divided into four groups: normal control group, untreated group, cyclosporine A (CsA)-treated group and KFSG-treated group. Except the rats in the normal control group, all the other rats received subcutaneous injection of collagen II to establish collagen-induced arthritis (CIA) models. Then the rats in each group were fed normal saline or corresponding drugs for four weeks. Total RNA was extracted from carpal and digital bones. The expressions of OPG, RANKL and M-CSF mRNAs were examined by real-time PCR. RESULTS: The total incidence of arthritis induced by collagen II in the rats was approximately 90%. The expression levels of RANKL and M-CSF mRNAs and the RANKL mRNA/OPG mRNA ratio in the untreated group, KFSG-treated group and CsA-treated group were all significantly higher than those in the normal control group, while the expression levels of OPG mRNA in those three groups were significantly lower than that in the normal control group. The expression level of OPG mRNA in the KFSG-treated group was obviously higher while the expression level of M-CSF mRNA and the RANKL mRNA/OPG mRNA ratio in the same group were both lower as compared with those in the untreated group. CONCLUSION: The molecular mechanism of effects of KFSG on bone erosion and destruction induced by rheumatoid arthritis is closely correlated with up-regulating the expression of OPG mRNA, down-regulating the expression of M-CSF mRNA and RANKL mRNA/OPG mRNA ratio.

Objective To explore the relationship between blood flow viscosity and femoral head necrosis after long-term glucocorticoid treatment (FHNG). Methods Blood and plasma viscosity, blood flow speed, RBC fragility, electrophoresis time, and the speed of blood flow were measured. Cellular ultrastructural changes of FHNG were studied with electron microscope. Results Blood viscosity of the treatment group increased obviously at the 8th week compared with that of control group (P

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

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

Objective To study the molecular pathway of osteoblastic differentiation induced by substance P (SP), a neurotransmitter. Methods Mesenchymal stem cells were isolated and cultured, and treated with SP or its receptor (NK1) antagonist to induce osteoblastic cell differentiation, respectively. Alkaline phosphatase activity was determined; Osterix gene expression was detected by RT-PCR after 1-2 weeks for three times. The data of each culture condition were analyzed using SPSS12.0 statistical software to determine whether the differences between conditions were significant. Results After 4-5 days' culture, bone marrow stromal cells became spindle-shaped, triangular or polygonic. They covered the plate surface, formed extensive cell sheets in each group after 11-12 days of culture, and then induced differentiation to osteoblast. SP up-regulated the important transcription factor Osterix gene expression significantly (P<0.05). Conclusion The up-regulation of Osterix gene expression by SP may stimulate osteoblastic cell differentiation. SP's regulation depends on its receptor NK1.

Objective To measure the width of space in front of the femoral neck at different age of normal children for diagnosis such as hip disease in children as bilateral transient synovitis of the hip. Methods Four hundred and twenty normal children below 14 years old were divided into 14 groups according to their age. Every group contained 30 children. They underwent bilateral ultrasonographic assessment. The width of space in front of the femoral neck was measured and collected. The mean width value in each group was compared mutually by statistical analysis (t test). Results The mean width of space in front of the femoral neck of normal children below 14 years old was 2.0 - 5.9 mm, the range was 1.2 - 7.8 mm. Conclusions The width of space in front of the femoral neck is different at different age of normal children, the mean value below 14 years old

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. [