1.Segmental defect in the radius of rabbits repaired by two kinds of bionic biphasic ceramic-like biologic bones
Shouping ZHANG ; Xiaoguang XIU ; Lili SUN
Chinese Journal of Tissue Engineering Research 2007;0(34):-
BACKGROUND:Natural biologic bone-derived products have been prepared by raw ox bone but not by swine vertebra. Previous research has indicated that biphasic ceramic-like biologic active bone made by swine vertebra has osteoinductive ability. OBJECTIVE:To investigate the feasibility of biphasic ceramic-like biologic active bone and biphasic ceramic-like biologic bone (BCBB) to repair the segmental defect in radius of rabbits. DESIGN,TIME AND SETTING:A randomized controlled animal experiment was performed at Institute of Orthopedics,the Fourth Military Medical University of Chinese PLA and Central Laboratory of Qingdao Medical College from October 2004 to October 2005. MATERIALS:Biphasic ceramic biologic bone was made of swine vertebra and sodium pyrophosphate after two calcinations at low temperature. The mixture which consisted of hydroxyapatite and tricalcium phosphate,sizing 0.3 cm ? 0.3 cm ? 1.5 cm was combined with type I collagen to make BCBB. Bone morphogenetic protein was mixed with type I collagen,and then the mixture was combined with biphasic ceramic biologic bone to make biphasic ceramic-like biologic active bone. METHODS:A total of 48 healthy Japanese rabbits were randomly divided into biologic active bone group,biologic bone group,and blank control group,with 16 rabbits per group. A segmental defect which was 15 mm along bilateral radius was established. Biphasic ceramic-like biologic active bone and BCBB were implanted into defect region,respectively,but implantation was not treated in the blank control group. MAIN OUTCOME MEASURES:Materials were harvested at weeks 2,4,8,12 for the gross observation under microscope. Tissue sections were selected for hematoxylin-eosin (HE) staining and Masson staining. RESULTS:① Gross observation:At 2 weeks,there were no differences between the two groups,and the materials were connected to bone bed with fibrous tissues. At 4 and 8 weeks,there was more new callus in biologic active bone group than in biologic bone group. At 12 weeks,some bionic biphasic ceramic-like biologic active bone were absorbed and new bone regenerated in biologic active bone group,being similar to appearance of host bone,but there were few callus in biologic bone group. In blank control group,bone defect could not be repaired and there were fibrous tissue in bone defect. ② Staining results:At 2 weeks after operation,there were no differences between the two groups,and the materials were connected to bone bed with fibrous tissues. At 4 and 8 weeks,more vessels and fibrous tissues grew into BCBB,new bone was formed,and bone connect was found between BCBB and bone bed in the biologic active bone group. At 12 weeks,in the biologic active bone group,more materials degraded,new bone was integrated with bone bed,and bone marrow-like structure was formed. At 12 weeks,the broken ends were sclerosis and blocked in the blank control group. CONCLUSION:Bionic biphasic ceramic-like biologic active bone characterizing by good bone induction and biocompatibility can remarkably repair the segmental defect in radius of rabbits. BCBB is perspective for repairing the segmental bone defect.
2.Preparation and performance of psoralen antibiotic biphasic ceramic bone
Xiaoguang XIU ; Shouping ZHANG ; Shuhua ZHANG ; Xiangli WANG
Chinese Journal of Tissue Engineering Research 2015;(25):3947-3951
BACKGROUND:In recent years, studies on the application of traditional Chinese medicine in bone tissue engineering are stil at the initial stage in China. Reports about psoralen antibiotic biphasic ceramic bone have not been seen in bone tissue engineering research. OBJECTIVE:To fabricate the psoralen antibiotic biphasic ceramic bone by vacuum evaporator and to observe the physicochemical properties, antibiotic activity and biocompatibility of the material. METHODS:Biphasic ceramic bone was prepared by twice low-temperature calcining pig vertebrae combined with sodium pyrophosphate, and then the ceramic bone was immersed in chitosan/psoralen compound solution to prepare psoralen antibiotic biphasic ceramic bone. The surface morphology was observed by scanning electron microscope, and the compressive strength was tested. Antibiotic activity of the psoralen antibiotic biphasic ceramic bone on Escherichia coli and Staphylococcus aureus was tested by microbiological methods. Mouse osteoblasts MC3T3-E1 were co-cultured with the psoralen antibiotic biphasic ceramic bone for 4 and 8 days, and the cel adhesion and proliferation on the scaffold surface were observed under the scanning electron microscope. RESULTS AND CONCLUSION:Psoralen antibiotic biphasic ceramic bone had natural pore structure with the trabecular bone, trabecular space and lumen system and exerted great antibiotic effect on Escherichia coli and Staphylococcus aureus. The compressive strength was (4.69±0.50) MPa. Mouse osteoblasts MC3T3-E1M could be adherent to the psoralen antibiotic biphasic ceramic bone and proliferate rapidly, suggesting the psoralen antibiotic biphasic ceramic bone has good cytocompatibility.
3.Investigation of the changes of plasma interleukin-6, interleukin-8, tumor necrosis factor-alpha in acute blood loss patients
Jun WANG ; Xiaoguang XIU ; Yanni SUN ; Shenglin ZHANG
Chinese Journal of Postgraduates of Medicine 2012;(33):4-6
Objective To investigate the changes and significance of plasma interleukin (IL)-6,IL-8,tumor necrosis factor-alpha (TNF-α) and nitric oxide synthase (NOS) in acute blood loss patients.Methods The levels of plasma IL-6,IL-8,TNF-α and NOS were determined in 25 patients with acute blood loss(blood loss group) and 25 healthy controls(control group) by enzyme linked immunosorbent assay.Result The levels of plasma IL-6,IL-8,TNF-α and NOS in blood loss group were higher than those in control group (0.284 ± 0.027 vs.0.204 ± 0.016,0.059 ± 0.079 vs.0.037 ± 0.039,0.460 ± 0.024 vs.0.372 ±0.018,0.637 ±0.054 vs.0.443 ±0.040,P<0.05 or <0.01).Conclusions First,the expressions of IL-6,IL-8,TNF-α and NOS are strongly induced at the circumstances of acute early stage blood loss which can cause inflammatory reaction,aggravate the damage of soft tissues and organs,and easy to lead the blood loss to uncontrolled hemorrhagic shock.Second,the expression of NOS is strongly induced at the circumstances of acute blood loss which should reduce the damage of soft tissue,and alleviate the hemorrhagic shock.Therefore,the levels of plasma IL-6,IL-8,TNF-α and NOS can estimate the illness prognosis and curative effect,which have important clinical instruction value for effective treatment of hemorrhagic shock.
4.SPECT cerebral perfusion imaging and its quantitative analysis for the assessment of stent implantation for cerebral artery stenosis
Lili JIN ; Xiaoguang SUN ; Gang HUANG ; Yan XIU ; Hongcheng SHI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2015;35(2):108-111
Objective To evaluate the role of SPECT cerebral perfusion imaging in assessing the stent implantation for cerebral artery stenosis.Methods A total of 35 patients (31 males,4 females,average age (63.9±10.8)years) with cerebral artery stenosis confirmed by DSA for cerebral artery stent implantation were retrospectively analyzed.99Tcm-ECD cerebral perfusion imaging was performed for all patients before and after stent implantation.The images were realigned and normalized by SPM 2.0 and then analyzed by Brain Search software for quantitative analysis.The brain was automatically separated to 210 functional areas according to Talarich map.The normalized averaged counts (NAC) of each area were calculated and compared with the data of 28 health controls (8 males,20 females,average age (35.8± 9.4) years).Less than 1.96s was defined as low perfusion lesions.The NAC values before and after stent implantation were compared for classifying improved from non-improved group.The mean number of lesions and Essen stroke risk score (ESRS) were analyzed between the two groups.The mean number of lesions and postoperative improvement rate of the internal carotid artery (ICA) occlusion and stenosis were compared.Paired rank sum test,two-sample t test,two-sample rank sum test and x2 test were used for statistical analysis.Results In 35 patients with low perfusion areas,20 were significantly improved after stent implantation.The mean number of lesions in the improved group (34.05± 14.41)was significantly higher than that in the non-improved group (22.93±17.24; t=2.067,P<0.05).The mean ESRS of the improved patients (14.8)was significantly lower than that of the non-improved patients (22.3,Z=2.24,P<0.05).The improvement rate of 28 cases with ICA stent implantation was (60.7%,17/28)higher than that of 7 cases with middle cerebral artery (MCA) stent implantation (3/7; P>0.05).The mean number of the ICA occlusion lesions (34.36± 14.31)was higher than that of the ICA stenosis lesions(31.35± 16.37),but the difference was not statistically significant(t=0.498,P>0.05).The improvement rate of the ICA occlusion was higher than that of the ICA stenosis (7/11 vs 10/17),but the difference was not statistically significant (P>0.05).Conclusion SPECT cerebral perfusion imaging and its quantitative analysis can evaluate the low perfusion lesions before stent implantation and predict the perfusion improvement after stent implantation.
5.Comparative evaluation on functions-safety of two TCM healthy foods on sale and discussion of relevant problems
Xiaoguang WANG ; Haizhou HUANG ; Xiu SHEN ; Xiaoliang ZHOU ; Wei LONG ; Yujun YAN ; Zewei ZHOU
Chongqing Medicine 2014;(12):1463-1467
Objective To conduct the comparative comprehensive evaluation on the actual healthy effects and safety of two kinds of healthy foods capsule A and B made of Chinese medicinal herbs on sale through the low-nutritional sub-health mice model com-bined with the benefit-damage index-general score(BDI-GS) approach ,and to perform the discussion on the relevant problems a-round healthy foods .Methods The experimental healthy ICR male mice during growth period were fed with maize low-nutritional feed and the mixed feed with 3 doses of 0 .25% ,0 .5% ,0 .75% healthy foods for 12 d and the mice body masses were recorded .Af-ter dissection ,9 items of the organ index and their BDI ,GS and serum biochemical indicators were performed the statistics .Results In the capsule A ,the medium and high dose groups manifested certain health-promoting effect ,while the slight negative effect exis-ted in the low dose group ,which was expressed in the GS values ;but in the capsule B ,3 doses all caused the damage to main internal organs in different degrees ,which was expressed in BDI<1 .0 and GS<9 .0 .Conclusion At present ,despite of possessing similar ingredients ,Chinese medicinal healthy foods in market are of greater differences in intrinsic qualities ,and even partial products have some adverse effect ,the healthy functions and safety are not enough to be fully ensured .Through the systematic evaluation of the BDI-GS system ,the criteria of marketing threshold for healthy foods will be increased so as to enhance their effects and safety level .
6.Mechanism by which Bushen Yiqi Huayu granule improves callus angiogenesis in osteoporotic rats after fracture operation
Jun WANG ; Zhiwei DONG ; Xiaodong WANG ; Xiaoguang XIU
Chinese Journal of Tissue Engineering Research 2024;28(21):3306-3312
BACKGROUND:Bushen Yiqi Huayu granule has the effect of replenishing qi and eliminating blood stasis,tonifying kidney and smoothing collages,and is often used in the treatment of osteoporosis.At present,there are few studies on the effect of Bushen Yiqi Huayu granule on the callus angiogenesis of osteoporotic fractures. OBJECTIVE:To explore the mechanism of Bushen Yiqi Huayu granule by up-regulating extracellular signal-regulated kinase/mitogen-activated protein kinases(ERK/MAPK)signaling pathway to improve callus angiogenesis after fracturing in osteoporotic rats. METHODS:(1)Bone marrow mesenchymal stem cells from osteoporotic SD rats and bone marrow monocytes from C57BL/6 mice were collected.MTT assay was used to detect different doses of Bushen Yiqi Huayu granule on bone mesenchymal stem cell toxicity.Bone mesenchymal stem cells and bone marrow monocytes were cultured in the medium supplemented with 0 and 1.5 mg/mL Bushen Yiqi Huayu granules,respectively,and osteogenic differentiation and osteoclast differentiation were carried out in vitro.(2)144 SD rats were randomly divided into sham operation group,model group,granule group and granule+PD98059 group with 36 rats in each group.The osteoporotic model was established in the model group,granule group and granule+PD98059 group,and only part of the adipose tissue near the ovary was removed in the sham operation group.8 weeks later,all rats received left tibial osteotomy.In the granule+PD98059 group,5 g/kg Bushen Yiqi Huayu granule was given intragastrically,and 0.3 mg/kg PD98059 was injected into the tail vein.The granule group was given 5 g/kg Bushen Yiqi Huayu granule,and the same volume of normal saline was injected into the tail vein.The sham operation group and model group were given an equal volume of normal saline,and the caudal vein was injected with an equal volume of normal saline.Drug administration was conducted once a day for 8 weeks.Fracture healing and callus angiogenesis were observed by X-ray,micro-computed tomography and microvascular perfusion angiography.Bone mineral density and mechanical strength of the callus were measured.The tibia was observed by hematoxylin-eosin staining and Masson staining.Western blot assay and immunohistochemistry were used to examine the expression of ERK/MAPK signaling pathway-related molecules. RESULTS AND CONCLUSION:(1)Compared with the 0 mg/mL group,the alkaline phosphatase activity,mineralization level,p-ERK1/2 and p-p38 MAPK expression levels of osteocytes increased(P<0.05),while the density and volume of osteoclasts decreased in the 1.5 mg/mL group(P<0.05).(2)Compared with the sham operation group,the fracture healing degree of the granule group was similar at 4 and 8 weeks,but there was no significant difference in Lane-Sandhu score,total callus volume,mineralized callus volume,mineralized callus volume/total callus volume,trabecular thickness,vascular number,spacing,thickness,vascular volume/total volume,bone mineral density,ultimate load of callus,stiffness,p-ERK1/2,p-p38 MAPK,p-IκB-α,and p-p65 expression levels(P>0.05).In the model group and granule+PD98059 group,fracture healing was slow,Lane-Sandhu score,total callus volume,mineralized callus volume,mineralized callus volume/total callus volume,trabecular thickness,vascular number,thickness,vascular volume/total volume,bone mineral density,ultimate load of callus,stiffness,p-ERK1/2,p-p38 MAPK,p-IκB-α,and p-p65 expression levels decreased(P<0.05),and vascular spacing increased(P<0.05),compared with the sham operation group.(3)It is indicated that Bushen Yiqi Huayu granule can improve fracture healing,promote callus angiogenesis and alleviate the symptoms of osteoporosis by enhancing the expression of the ERK/MAPK signaling pathway-related molecules in osteoporotic rats.
7.Identification of serum peptide biomarker for ovarian cancer diagnosis by Clin-TOF-II-MS combined with magnetic beads technology
Lin XIU ; Ning LI ; Wenpeng WANG ; Feng CHEN ; Guangwen YUAN ; Yangchun SUN ; Rong ZHANG ; Xiaoguang LI ; Jing ZUO ; Nan LI ; Wei CUI ; Lingying WU
Chinese Journal of Oncology 2021;43(11):1188-1195
Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.
8.Identification of serum peptide biomarker for ovarian cancer diagnosis by Clin-TOF-II-MS combined with magnetic beads technology
Lin XIU ; Ning LI ; Wenpeng WANG ; Feng CHEN ; Guangwen YUAN ; Yangchun SUN ; Rong ZHANG ; Xiaoguang LI ; Jing ZUO ; Nan LI ; Wei CUI ; Lingying WU
Chinese Journal of Oncology 2021;43(11):1188-1195
Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.