Mechanism action of Chinese herbal compound and target network pharmacology of / 中国骨伤

OBJECTIVE@#To explore compounds, targets and mechanism of @*METHODS@#The known effective Chinese herbal compound of YG pill was searched from traditional Chinese medicine integrated database(TCMID). Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM) was used to predict target of components;DisGeNET and artificial literature reading were used to obtain targets of osteoporosis and bone remodeling;Cytoscape 3.7.1 software and its plug-ins BiN-GO and ClueGO were used to enrich the GO annotation and pathwaysof the related targets, and validation of the predicted target of YG pill were validated by 87 differentially expressed proteins in postmenopausal osteoporosis and postmenopausal osteoporosis disease models in postmenopausal patients with normal bone mass from the previous serum proteomics data.@*RESULTS@#Totally 392 compounds were retrieved from YG pill, including 83 sovereign drugs (monkshood, cinnamon, deerhorn gelatin), 127 ministerial drugs (prepared rehmannia root, dogwood, wolfberry fruit and Chinese yam) and 182 supplementary drugs (cuscuta chinensis, eucommia ulmoides and Chinese angelica). Among them, there were 4 same compounds between sovereign drug and ministerial drug, 1 same compound between sovereign drug and supplementary drug, and 14 same compounds between ministerial drug and supplementary drug. Totally 2 112 trusted targets were identified, included 775 sovereign drugs, 1 483 ministerial drugs and 1 491 supplementary drugs;227 targets were selected from YG pill for treating osteoporosis, which participate in nearly 20 process of metabolic process, cell differentiation and biology, and data mining revealed that the process involved bone remodeling and bone mineralization. Acting site of cell mainly inclded 9 kinds of cell which had 13 molecular function. Results of KEGG metabolic pathway enrichment analysis showed 137 signal passages were obviously enriched. Among them, classical osteoclast differentiation signal passages and relative estrogen regulates signaling pathways of menopause were widely distributed in 27 signal passages. Sixtargets were screened by target validation, such as AGT, FGA, APOE, DKK3, P4HB and RAB7A.@*CONCLUSION@#The characteristics of multi-targets and multi-pathways of YG pill for the treatment of osteoporosis were clarified, which provided a clear direction for the in-depth research. The pharmacodynamic components of YG pill include 36 compounds, and their main action targets include FGA, AGT, APOE, DKK3, P4HB and RAB7A.

Identification of human serum protein targets of Qianggu Decoction () in primary type I osteoporosis based on tandem mass tag labeling and liquid chromatography-tandem mass spectrometry technology / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the serum protein targets of Qianggu Decoction (, QGD) on treating osteoporosis by the proteomics analysis using tandem mass tag (TMT) and liquid chromatographytandem mass spectrometry (LC-MS/MS).</p><p><b>METHODS</b>Twenty serum protein samples were recruited (10 patients with primary type I osteoporosis before and after QGD treatment) and the high abundance ratios protein was removed, two serum samples were extracted and labeled with TMT reagent. Then, mass spectrometric detection, identification of differentially expressed proteins and bioinformatics analysis of differentially expressed proteins were carried out.</p><p><b>RESULTS</b>A total of 60 proteins were identified, within a 99% confidence interval, to be differentially regulated of which, 34 proteins were up-regulated and 26 proteins were down-regulated. Differentially expressed proteins analyzed by Gene Ontology (GO) annotation mainly get involved in 12 different biological processes, 7 types of cellular components, and 6 kinds of molecular functions. Angiotensinogen (AGT), stromelysin-1 (MMP3), heparanase (HPSE) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were screened as candidate protein targets of QGD treatment, which were related to metabolic mechanism of bone remodeling and/or bone collagen of osteoporosis. By the utilization of the protein-protein interaction network analysis tool named STRING10.0, it showed that AGT, MMP3, HPSE and GAPDH were located in the key node of the protein-protein interactions network. Furthermore, AGT, MMP3, HPSE and GAPDH were found to be directly related to BMP, MAPK, Wnt, SMAD and tumor necrosis factor ligand superfamily member 11 (TNFSF11) families.</p><p><b>CONCLUSIONS</b>The proteomics analysis by using TMT combined with LC-MS/MS was a feasible method for screening the potential therapeutic targets associated with QGD treatment. It suggests that AGT, MMP3, HPSE and GAPDH may be candidate protein targets of QGD treatment which can be used as therapeutic effect monitor and early diagnosis of primary type I osteoporosis.</p>

Effect and mechanism of total flavone of epimedium on primary callus formation in ovariectomized rats with fractures / 中国骨伤

<p><b>OBJECTIVE</b>To explore the effects and related mechanisms of total flavone of epimedium treatment(TFE)on primary callus for mation in ovariectomized rats.</p><p><b>METHODS</b>Forty male SD rats weighted from 209 to 246 g and aged 6 to 8 weeks were selected. Six weeks after ovariectomy a femur fracture model with middiaphyseal segment fracture was established, estimated and randomly divided into TFE group (150 mg·kg⁻¹·d⁻¹) and control group(received saline). HE staining was used to evaluate the morphologic difference of primary callus during the bone callus healing between these two groups. The relative expression of Runt-related transcription factor 2(Runx2) mRNA in the callus was identified by real-time polymerase chain reaction. Immunohistochemical technique was used to observe the Casein kinase 2-interacting protein 1(CKIP-1) protein level in the callus of the two groups. Maximum fracture load was tested by three point bend test.</p><p><b>RESULTS</b>The BMD, primary callus volume, trabecular member(Tb.N) and trabecular thickness(Tb.Th) were higher in TFE group than that in control group(<0.001). The Tb.N and Tb.Th of primary callus were higher in TFE group than control group (=0.001). The volume and bone volume/tissue volume of primary callus were in TFE group than control group(<0.01). The trabecular separation(Tb.Sp) of primary callus were in control group higher than TFE group(<0.01). The HE staining of the 6 week slices showed that the degree of cartilage ossification in callus of the TFE group was significantly higher than that in control group under high magnification. Real-time PCR revealed that the comparative expression of Runx2 mRNA in control group was higher than that in TFE group(<0.001); the positive number of CKIP-1 was less in TFE group than that in control group (<0.001). TFE could increase the maximum load of the primary callus (<0.001).</p><p><b>CONCLUSIONS</b>TFE can promote the cartiage ossification of callus in ovariectomized rats, enhancing the bone strength and bone quality in the process of fracture healing via the CKIP-1/Runx2 pathway.</p>

Clinical observation of improved proximal femoral locking plate in treating osteoporotic intertrochanteric fractures / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the effects of proximal femoral locking plate (PFP) in treating osteoporotic intertrochanteric fractures and to analyze the failure cases.</p><p><b>METHODS</b>Totally 32 patients with osteoporotic intertrochanteric fractures of Evans I and II were treated with improved locking PFP, including 17 males and 15 females with an average age of 77.3 years old ranging from 70 to 86 years old. After operation, according to Harris hip scores, the hip function and therapeutic effects were evaluated.</p><p><b>RESULTS</b>The observed 32 patients' operative time was (60.5±15.7) min, intraoperative blood loss was (128.8±73.6) ml;perioperative blood transfusion was (224.0±72.7) ml. Hospitalization time was from 14 to 20 d with an average of 17.2 d. All patients were followed up from 6 to 18 months with an average of 14.1 months. The fracture healing time was from 3 to 6 months with an average of 3.1 months. One patient occurred internal fixation loosening and screw backward, 4 cases occurred urinary tract infection, 1 patient died of cardiovascular disease for 6 months postoperative, 2 patients died of a stroke for 1 year postoperative. No incision deep infection, peri internal fixation fractures, lower extremity deep venous thrombosis, internal fixation breakage, nonunion, severe coax vara and coax valgus occurred. The final Harris score was 89.74±6.84, the result was excellent in 10 cases, good in 16 cases, fair in 4 cases, and poor in 2 cases.</p><p><b>CONCLUSIONS</b>Locking PFP can provide relative stable fixation to proximal end of osteoporotic femoral fractures, which is a good choice for the treatment of intertrochanteric fractures. It could provide stableness of fractures and bone union, even avoid screws loose or slide out.</p>