The pathological progression of steroid-induced osteonecrosis of the femoral head caused by oxidative stress-induced osteoblast ferroptosis / 中国组织工程研究

BACKGROUND:Studies have shown that imbalance of bone metabolism during glucocorticoid-induced osteonecrosis of the femoral head necrosis is closely related to oxidative stress. OBJECTIVE:To investigate the pathological mechanism by which oxidative stress-induced ferroptosis promote apoptosis in osteoblasts involved in steroid-induced osteonecrosis of the femoral head. METHODS:General data and serum specimens were collected from 47 patients with steroid-induced osteonecrosis of the femoral head.In addition,six femoral head specimens were collected from these patients.According to the Association Research Circulation Osseous(ARCO)staging system,serum specimens were grouped into ARCO Ⅱ,Ⅲ,and IV,while femoral head specimens were classified into ARCO Ⅲ and IV.Serum levels of malondialdehyde and superoxide dismutase 1 were measured.The protein expression of superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 in the femoral head was detected and verified by Data independent acquisition(DIA)for quantitative sequencing,western blot and alkaline phosphate detection. RESULTS AND CONCLUSION:The ARCO stage of patients with steroid-induced osteonecrosis of the femoral head was independent of age,sex and necrotic side.The serum levels of malondialdehyde and superoxide dismutase 1 were higher in patients with ARCO stage Ⅲ compared with those with ARCO stage Ⅱ and IV.The results of DIA protein quantification showed that the function of differential proteins was mainly related to redox.The levels of superoxide dismutase 1,glutathione peroxidase 4,and Bcl-2 in the necrotic region were lower than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.Western blot verified the results of DIA protein quantification.The alkaline phosphatase activity was lower in the necrotic region than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.In the necrotic and sclerotic regions,the function of differential proteins was also related to redox,and superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 protein expression and alkaline phosphatase activity were lower in the necrotic area than in the sclerotic region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.To conclude,glucocorticoids can influence the progression of steroid-induced osteonecrosis of the femoral head by upregulating oxidative stress levels,inducing osteoblast ferroptosis,and inhibiting osteogenic function.

Osteoclast-mediated pain and collapse mechanisms in the femoral head necrosis with bone marrow edema / 西安交通大学学报(医学版)

【Objective】 To explore pain and collapse mechanisms in fosteonecrosis of the femoral head (ONFH) with bone marrow edema (BME). 【Methods】 ONFH patients at ARCO Ⅲ stage who underwent total hip arthroplasty in the First Affiliated Hospital of Guangzhou University of Chinese Medicine were enrolled; the femoral head samples, clinical and imaging data were collected. These patients were divided into BME group and non-BME group according to the MR data in one week preoperative. Hematoxylin-eosin and Sirius red staining were performed to observe the morphological changes in bone tissue of femoral head specimens. Western blotting and qPCR were used to semi-quantitatively analyze the expression levels of CTSK, RANKL, and Netrin-1 proteins and mRNA in different regions of the bone tissue. 【Results】 Clinical and imaging data showed that ONFH patients with BME had significantly higher scores of VAS than ONFH patients without BME. Hematoxylin-eosin staining showed that bone structure disorder and a large number of empty bone lacunae were found in the necrotic areas in both groups, but there exited significant granulation tissue in the BME group, and spindle-shaped fibroblastic cells and inflammatory cells aggregated in the repaired region. Sirius red staining revealed the necrotic and sclerotic areas were accumulated with many collagenous fiber in the BME group. The results of Western blotting and qPCR showed that Netrin-1 expressions in the necrotic, sclerotic and health areas in the BME group were higher than those in the non-BME group (P<0.05), while osteoclast related proteins and mRNA expressions of the necrotic and sclerotic areas in the BME group was higher than those in the non-BME group (P<0.05). 【Conclusion】 All these findings indicated that hip pain was positively correlated with femoral head necrosis with BME, hyperactive osteoclasts participated in the femoral head collapse with BME, and the upregulated expression of Netrin-1 mediated the pain mechanism.

Diagnosis and treatment of acute pancreatitis complicated with splenic infarction and literature review / 中国医师杂志

Objective:To investigate the etiology, pathogenesis, clinical manifestations, and treatment of acute pancreatitis (AP) complicated with spleen infarction.Methods:A case of AP combined with splenic infarction was retrospectively analyzed and the literature was reviewed.Results:AP complicated with splenic infarction suggested that the patient′s condition was serious. The impairment of splenic immune function caused by splenic infarction may be an important cause of severe acute pancreatitis (SAP). Early detection and active treatment can obtain a good prognosis, and anticoagulant or antiplatelet aggregation treatment was not the key treatment.Conclusions:AP combined with splenic infarction may be an risk factor for SAP.

Impact of diabetes mellitus on pacing parameters and complications in patients with implantation of ;permanent artificial cardiac pacemaker / 心血管康复医学杂志

Objective:To observe the impact of diabetes mellitus (DM)on pacing parameters and postoperative com-plications in patients With implantation of permanent artificial cardiac pacemaker.Methods:A total of 80 patients With sick sinus syndrome,Who received implantation of permanent artificial cardiac pacemaker from Jun 2008 to Jun 2011,Were enrolled.According to complicated With DM or not,they Were divided into DM group (n=40)and non-DM control group (n=40).Pacing parameters and postoperative complications Were compared betWeen tWo groups.Results:There Were no significant difference in atrial and ventricular pacing threshold,sensing and of pace-maker impedance in baseline betWeen tWo groups (P>0.05).All parameters of pacemaker increased in tWo groups after implantation 12 months;compared With non-DM control group,there Were significant increase in pacing threshold [atrial:(0.59±0.23)V vs.(0.67±0.25)V,ventricular:(0.47±0.28)V vs.(0.54±0.35)V],sens-ing [atrial:(2.33±1.16)mV vs.(2.92±1.36)mV,ventricular:(12.21±4.82)mV vs.(12.77±5.36)mV], impedance [atrial:(537.12±115.32)Ωvs.(662.48±235.26)Ω,ventricular:(602.48±222.46)Ωvs.(762.41± 235.38)Ω]of pacemaker in DM group,P<0.05 or <0.01;and incidence rate of postoperative complications (12.5%)in DM group Was significantly higher than that of non-DM control group (5%),P<0.05.Conclusion:Electrocardiographic reconstruction is more severe in SSS patients complicated DM,in these patients postoperative complication incidence significantly elevates.

Pharmacokinetic study on acetoside in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a HPLC method for determining acetoside in rat plasma and to investigate the pharmacokinetic characteristics of acetoside in rats.</p><p><b>METHOD</b>Six rats were orally administered with 150 mg x kg(-1) acetoside and their blood samples were collected at different time points. The plasma concentration of acetoside was determined by reserved HPLC, and the pharmacokinetic parameters were calculated by DAS 2.0 software.</p><p><b>RESULT</b>The regression equation of acetoside in rats plasma was Y = 3.509 8X-0.096 8 (r = 0.996 8), which showed a good linear relation at 0.125-2.5 mg x L(-1). The method showed a recovery of more than 85%, and both inter-day and intra-day RSDs were less than 15%. After the oral administration of 150 mg x kg(-1) acetoside, the concentration-time curves of acetoside were expressed in a open two-compartment model. The main pharmacokinetics parameters of T(max), C(max), t(1/2alpha), t(1/2beta), AUC(0-t), AUC(0-infinity), CL/F, V/F and K(a) were respectively 0.36 h, 1.126 mg x L(-1), 0.759, 4.842 h, 3.134, 3.766 mg x h x L(-), 87.089 L x h(t) x kg(-1), 207.704 L x kg(-1) and 6.345 h(-1) respectively.</p><p><b>CONCLUSION</b>It is first time to establish such a HPLC method to determine the concentration of acetoside in plasma. The method is so highly specified and sensitive that it can ble used in quantitative analysis in vivo on acetoside.</p>

Effect of acteoside on learning and memory impairment induced by scopolamine in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study on the effect of acteoside on learning and memory of dementia mice.</p><p><b>METHOD</b>Mice were orally administered with acteoside for 10 days. Scopolamine was used to establish the acquired learning disability in mice. Their learning and memory were detected with a behavioral experiment (step-down test). After the behavior test, corticocerebral and hippocampus tissues of mice were detected with biochemical indexes, including GSH-Px, T-SOD, MDA, TChE and contents of protein in brain tissues.</p><p><b>RESULT</b>Mice were administered with acteoside for 10 d in advance to alleviate the acquired learning disability induced by scopolamine. Compared with the model group, acteoside increased the latency period in the step-down test and reduced error times. Besides, acteoside increased the activity of GSH-Px, T-SOD, TChE and protein content in their brain tissues, but decreased MDA content.</p><p><b>CONCLUSION</b>Acteoside can significantly alleviate the acquired learning disability in mice induced by scopolamine. Its mechanism may be related with its effect of inhibiting the generation of free radicals in mice and improving the function of the central cholinergic system.</p>

Expression of Toll-like receptor 4 and tumor necrosis factor-α on peripheral-blood mononuclear cells and their correlation with myocardial perfusion in patients with diabetic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the expression of Toll-like receptor 4 (TLR4) and tumor necrosis factor-α (TNF-α) on peripheral-blood mononuclear cells (PBMCs) and their correlation with myocardial perfusion in patients with diabetic cardiomyopathy (DCM).</p><p><b>METHODS</b>The expression of TLR4 and TNF-α mRNA on PBMCs were examined by SYBR Green I real-time quantitative reverse transcription polymerase chain reaction (RT-PCR), the levels of TLR4 and TNF-α were examined by flow cytometric analysis and enzyme-linked immuno sorbent assay (ELISA) on DCM group (n = 20), Type 2 diabetic group (n = 22) and control group (n = 20). Myocardial perfusion was visualized by single-photon emission computed tomography (SPECT).</p><p><b>RESULTS</b>The expressions of TLR4 and TNF-α mRNA/protein on PBMCs in DCM group were significantly higher than in Type 2 diabetic group, and higher in Type 2 diabetic group than in control groups (P < 0.05); summed stress score (SSS) and summed rest score (SRS) of myocardial perfusion in DCM group were significantly higher than in Type 2 diabetic group, and higher in Type 2 diabetic group than in control groups (P < 0.01). The expression of TLR4, TNF-α was positively correlated with SSS (r = 0.75, P < 0.05; r = 0.931, P < 0.005) and SRS (r = 0.78, P < 0.005; r = 0.789, P < 0.005). SSS and SRS in DCM group were also positively correlated with soluble vascular cell adhesion molecule-1 (sVCAM-1) (r = 0.728, P < 0.005; r = 0.738, P < 0.005) but there was no correlation between SSS and SRS and brain natriuretic peptide, LVEF, E/A, HbA1c, FBG, FIN and LDL-C (P > 0.05).</p><p><b>CONCLUSION</b>The increased expression of TLR4 and TNF-α mRNA/protein on PBMCs and increased serum sVCAM-1 is linked with reduced myocardial perfusion in DCM group. TLR4 and TNF-α may thus play a critical role in the myocardial perfusion inflammation injury in these patients.</p>

Expression of transforming growth factor-beta 1 in rabbit anastomotic tissues using three kinds of sutures after tracheotomy: Which one has better histocompatibility? / 中国组织工程研究

BACKGROUND: Appropriate anastomosis materials can improve success rate of trachea and bronchus reconstruction.Common domestic suture materials include silk suture, dacron and synthesized absorbable suture. However, the suture with best effects in preventing and lightening scar granulation hyperplasia and luminal stenosis remains Uncertain.OBJECTIVE: To compare the influence of three kinds of suture materials on histopathological changes of anastomotic stoma and transforming growth factor-β_1 (TGF-β_1) expression in rabbits following tracheotomy.DESIGN, TIME AND SETTING: A randomized, controlled animal experiment and histopathological observation were performed at the Animal Experimental Department, Nanhua University from September 2005 to October 2006.MATERIALS: Artificial absorbable suture was purchased from Brazil Johnson & Johnson Professional Products; silk suture and dacron were purchased from Hangzhou Fuyang Medical Suture Factory and Hangzhou Huawei Medical Products Co., Ltd.METHODS: A total of 36 New Zealand healthy adult rabbits, regardless of gender, weighing 1.6-2.0 kg, were randomly divided into silk, dacron and artificial absorbable suture groups with 12 animals in each group. The end-to-end anastomosis following tracheotomy was performed using silk, dacron and artificial absorbable suture, respectively.MAIN OUTCOME MEASURES: The pathological changes and TGF-β_1 level around the sutures 1, 2, 4 weeks post operation were observed.RESULTS: A total of 36 rats were included in final analysis. There were no difference in anastomotic healing between three groups 1 and 2 weeks postoperatively, with a great amount of inflammatory cell infiltration, mainly neutrophil, around the sutures.Moreover, bleeding in the focus and foreign body grannuloma were found. At 4 weeks postoperatively, foreign body grannuloma formed accompanied with obvious firboplasia in silk and dacron groups, and the sutures in the artificial absorbable suture group were absorbed. Compared with 1 and 2 weeks postoperatively, the expression of TGF-β_1 was slightly decreased in silk and dacron groups at 4 weeks (P > 0.05), but the absorbable suture group significantly decreased (P < 0.05).CONCLUSION: Of three kinds of suture materials, artificial absorbable suture exhibited good histocompatibility, effectively reducing inflammatory reaction and benefiting the prevention and lightening of formation of pathological scar after tracheal surgery.

A new hypoxic brain damage model in the neonatal rat / 中国当代儿科杂志

<p><b>OBJECTIVE</b>This study aimed to prepare a hypoxic brain damage model in the neonatal rat using a new approach, 0% oxygen exposure, and to explore the reliability and advantages of the new model.</p><p><b>METHODS</b>Seven-day-old Wistar rats were randomly exposed to either 7 minutes of 0% oxygen, to the conventional Rice-Vannucci method (ischemia + 2 hrs hypoxia exposure), or to left common carotid artery ligation (ischemia). Rat pups which were not subjected to any hypoxia-ischemia treatment were used as the control group. Brain water content and neuronal apoptosis were measured. Neurofunctional assessment was performed. Brain pathological changes were observed using hematoxylin and eosin staining.</p><p><b>RESULTS</b>The water content (88.96+/-0.29%) and apoptosis of neurons (31.52+/-5.45%) of the left brain in the 0% oxygen group were significantly higher than those of the ischemic and the control groups (P<0.01), and similar to those in the Rice-Vannucci group. The water content (88.68+/-0.24%) and apoptosis of neurons (30.85+/-5.38%) of the right brain in the 0% oxygen group were significantly higher than those of the Rice-Vannucci, the ischemic and the control groups (P<0.01). Both side brains of the 0% oxygen group showed pathological injuries, but only left brain of the Rice-Vannucci group had pathological changes. No pathological abnormalities were seen in the ischemic and the control groups. Significant neurofunctional impairments were found in the 0% oxygen and the Rice-Vannucci groups.</p><p><b>CONCLUSIONS</b>A hypoxic brain damage model of neonatal rat was successfully prepared using 7 minutes 0% oxygen exposure. The new approach appears to be simple and reliable.</p>