Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a.

BACKGROUND: Knee osteoarthritis (KOA) is a common orthopedic condition with an uncertain etiology, possibly involving genetics and biomechanics. Factors like changes in chondrocyte microenvironment, oxidative stress, inflammation, and immune responses affect KOA development. Early-stage treatment options primarily target symptom relief. Mesenchymal stem cells (MSCs) show promise for treatment, despite challenges. Recent research highlights microRNAs (miRNAs) within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression. This suggests exosomes (Exos) as a promising avenue for future treatment. While these findings emphasize the need for effective KOA progression management, further safety and efficacy validation for Exos is essential. AIM: To explore miR-29a's role in KOA, we'll create miR-29a-loaded vesicles, testing for early treatment in rat models. METHODS: Extraction of bone marrow MSC-derived extracellular vesicles, preparation of engineered vesicles loaded with miR-29a using ultrasonication, and identification using quantitative reverse transcription polymerase chain reaction; after establishing a rat model of KOA, rats were randomly divided into three groups: Blank control group injected with saline, normal extracellular vesicle group injected with normal extracellular vesicle suspension, and engineered extracellular vesicle group injected with engineered extracellular vesicle suspension. The three groups were subjected to general behavioral observation analysis, imaging evaluation, gross histological observation evaluation, histological detection, and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis. RESULTS: General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain, gait, joint mobility, and swelling compared to the blank control group. Additionally, the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group. Imaging examination results showed that the blank control group had the fastest progression of arthritis, the normal extracellular vesicle group had a relatively slower progression, and the engineered extracellular vesicle group had the slowest progression. Gross histological observation results showed that the blank control group had the most obvious signs of arthritis, the normal extracellular vesicle group showed signs of arthritis, and the engineered extracellular vesicle group showed no significant signs of arthritis. Using the Pelletier gross score evaluation, the engineered extracellular vesicle group had the slowest progression of arthritis. Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group, and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition. Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group. Compared to the normal extracellular vesicle group, the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells. CONCLUSION: Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability, thereby protecting articular cartilage, and slowing the progression of KOA.

Tranexamic versus aminocaproic acids in patients with total hip arthroplasty: a retrospective study.

BACKGROUND: Recently, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) have been applied in total hip arthroplasty (THA). However, doubts in clinicians' minds about which medicine is more efficient and economical in THA need to be clarified. Therefore, this study compared the efficacy and cost of the intraoperative administration of TXA and EACA per surgery in decreasing perioperative blood transfusion rates in THA. METHODS:  This study enrolled patients who underwent THA between January 2019 to December 2020. A total of 295 patients were retrospectively divided to receive topical combined with intravenous TXA (n = 94), EACA (n = 97) or control (n = 104). The primary endpoints included transfusions, estimated perioperative blood loss, cost per patient and the drop in the haemoglobin and haematocrit levels. RESULTS: Patients who received EACA had greater total blood loss, blood transfusion rates, changes in HGB levels and mean cost of blood transfusion per patient (P < 0.05) compared with patients who received TXA. In addition, both TXA and EACA groups had significantly fewer perioperative blood loss, blood transfusion, operation time and changes in haemoglobin and haematocrit levels than the control group (P < 0.05). Cost savings in the TXA and EACA groups were 736.00 RMB and 408.00 RMB per patient, respectively. CONCLUSIONS: The application of perioperative antifibrinolytics notably reduces the need for perioperative blood transfusions. What's more, this study demonstrated that TXA is superior to EACA for decreasing blood loss and transfusion rates while at a lower cost per surgery. These results indicate that TXA may be the optimum antifibrinolytics for THA in Chinese area rather than EACA.

Vortex evolution patterns for flow of dilute polymer solutions in confined microfluidic cavities.

Flow instability in confined cavities has attracted extensive interest due to its significance in many natural and engineering processes. It also has applications in microfluidic devices for biomedical applications including flow mixing, nanoparticle synthesis, and cell manipulation. The recirculating vortex that characterizes the flow instability is regulated by the fluid rheological properties, cavity geometrical characteristics, and flow conditions, but there is a lack of quantitative understanding of how the vortex evolves as these factors change. Herein, we experimentally study the flow of dilute polymer solutions in confined microfluidic cavities and focus on a quantitative characterization of the vortex evolution. Three typical patterns of vortex evolution are identified in the cavity flow of dilute polymer solutions over a wide range of flow conditions. The geometrical characteristics of the cavity are found to have little effect on the patterns of vortex evolution. The geometry-independent patterns of vortex evolution provide us an intuitive paradigm, from which the interaction and competition among inertial, elastic and shear-thinning effects in these cavity-induced flow instabilities are clarified. These results extend our understanding of the flow instability of complex fluids in confined cavities, and provide useful guidelines for the design of cavity-structured microfluidic devices and their applications.

Relationship Between Blood Flow and Collapse of Nontraumatic Osteonecrosis of the Femoral Head.

BACKGROUND: To investigate the collapse mechanism in osteonecrosis of the femoral head (ONFH), we studied the relationship between the femoral head (FH) blood circulation changes and the collapse area histomorphometry characteristics. METHODS: A technique involving microvascular perfusion of the FH in vitro to reconstruct the vessels in the FH at different stages of nontraumatic ONFH (40 cases). In addition, we also examined the histomorphometry characteristics in the collapse area during ONFH at different stages using the hard tissue section technique. To investigate the blood supply changes in the FH on pathological involved in the FH collapse process. RESULTS: The results showed that in all FHs, the collapse area always involved the margin of the necrotic lesion of the lateral column. Histologically, the fracture occurred between the thickened and necrotic trabeculae at the junction. We found that the collapse started at the lateral column of the FH in the necrotic lesion and that the lateral column was ischemic, which caused the FH to begin to collapse. CONCLUSIONS: Based on the above findings, the relationship between associations of the blood circulation to the collapse showed that if a portion of the blood supply of the lateral column (the superior retinacular artery) was preserved, the prognosis of the natural progression of the diseases was improved, the collapse rate was low and collapse occurred later. The blood circulation of artery in the lateral column was good, and the FH maintained an intact shape even if the internal region was ischemic. Therefore, we can predict the collapse of the FH by measuring the blood flow in the lateral area of the FH, thus providing guidance for the selection of FH-preserving clinical therapy in young and middle-aged patients. CLINICAL RELEVANCE: This work provides a proof of how to predict the collapse of the FH by measuring the blood flow, providing guidance for FH-preserving clinical therapy in young and middle-aged patients.

The 2021 Association Research Circulation Osseous Classification for Early-Stage Osteonecrosis of the Femoral Head to Computed Tomography-Based Study.

BACKGROUND: The Association Research Circulation Osseous developed a novel classification for early-stage (precollapse) osteonecrosis of the femoral head (ONFH). We hypothesized that the novel classification is more reliable and valid when compared to previous 3 classifications: Steinberg, modified Kerboul, and Japanese Investigation Committee classifications. METHODS: In the novel classification, necrotic lesions were classified into 3 types: type 1 is a small lesion, where the lateral necrotic margin is medial to the femoral head apex; type 2 is a medium-sized lesion, with the lateral necrotic margin being between the femoral head apex and the lateral acetabular edge; and type 3 is a large lesion, which extends outside the lateral acetabular edge. In a derivation cohort of 40 early-stage osteonecrotic hips based on computed tomography imaging, reliabilities were evaluated using kappa coefficients, and validities to predict future femoral head collapse by chi-squared tests and receiver operating characteristic curve analyses. The predictability for future collapse was also evaluated in a validation cohort of 104 early-stage ONFH. RESULTS: In the derivation cohort, interobserver reliability (k = 0.545) and intraobserver agreement (63%-100%) of the novel method were higher than the other 3 classifications. The novel classification system was best able to predict future collapse (P < .05) and had the best discrimination between non-progressors and progressors in both the derivation cohort (area under the curve = 0.692 [0.522-0.863], P < .05) and the validation cohort (area under the curve = 0.742 [0.644-0.841], P = 2.46 × 10-5). CONCLUSION: This novel classification is a highly reliable and valid method of those examined. Association Research Circulation Osseous recommends using this method as a unified classification for early-stage ONFH. LEVEL OF EVIDENCE: Level III, diagnostic study.

In vivo biocompatibility evaluation of Zn-0.05Mg-(0, 0.5, 1wt%)Ag implants in New Zealand rabbits.

Bio-absorbable Zn alloys have been attractive replacements for the traditionally permanent implants due to their reasonable mechanical strength and elongation, degradation rate, and biocompatibility. The hybridization addition of Mg and Ag elements could greatly improve the mechanical properties and antibacterial ability of Zn, respectively. In the present paper, in vivo biocompatibility for the Zn-0.05Mg-(0, 0.5, 1 wt%) Ag implants in New Zealand rabbit was qualitatively evaluated during the implantation periods of 4, 12, and 24 weeks. The blood serum biochemical parameters and in vivo integrity of the implants in the live rabbits were monitored by using clinical chemistry analyzing and X-ray radiographic imaging techniques during the implantation process, respectively. There is no great difference in the serum biochemical indicator between the implanted rabbits and the control group. Especially the levels of serum Zn and serum Mg normalize after implantation of 24 weeks. The interfacial adherence between the implants and newly formed bones, and the histopathological morphology of heart, liver, and kidney were observed morphologically under the microscope. The new bones formed and grew surrounding the implants after 12 weeks' post-operation, which were well joined with the original cortical bones after post-implantation of 24 weeks. The heart, liver and kidney were not negatively influenced as evidenced from the serum biochemical indicators and morphologies of the tissues. Zn-0.05Mg-(0, 0.5, 1 wt%) Ag alloys are proved to be in vivo biocompatible and potential candidates for the biodegradable medical implants.

Magnesium and vitamin C supplementation attenuates steroid-associated osteonecrosis in a rat model.

Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested in vitro. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. In vitro study showed promoting osteoblast differentiation effect of VC, and anti-inflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON.

The 2019 Revised Version of Association Research Circulation Osseous Staging System of Osteonecrosis of the Femoral Head.

BACKGROUND: The Association Research Circulation Osseous (ARCO) presents the 2019 revised staging system of osteonecrosis of the femoral head (ONFH) based on the 1994 ARCO classification. METHODS: In October 2018, ARCO established a task force to revise the staging system of ONFH. The task force involved 29 experts who used a web-based survey for international collaboration. Content validity ratios for each answer were calculated to identify the levels of agreement. For the rating queries, a consensus was defined when more than 70% of the panel members scored a 4 or 5 rating on a 5-point scale. RESULTS: Response rates were 93.1%-100%, and through the 4-round Delphi study, the 1994 ARCO classification for ONFH was successfully revised. The final consensus resulted in the following 4-staged system: stage I-X-ray is normal, but either magnetic resonance imaging or bone scan is positive; stage II-X-ray is abnormal (subtle signs of osteosclerosis, focal osteoporosis, or cystic change in the femoral head) but without any evidence of subchondral fracture, fracture in the necrotic portion, or flattening of the femoral head; stage III-fracture in the subchondral or necrotic zone as seen on X-ray or computed tomography scans. This stage is further divided into stage IIIA (early, femoral head depression ≤2 mm) and stage IIIB (late, femoral head depression >2 mm); and stage IV-X-ray evidence of osteoarthritis with accompanying joint space narrowing, acetabular changes, and/or joint destruction. This revised staging system does not incorporate the previous subclassification or quantitation parameters, but the panels agreed on the future development of a separate grading system for predicting disease progression. CONCLUSION: A staging system has been developed to revise the 1994 ARCO classification for ONFH by an expert panel-based Delphi survey. ARCO approved and recommends this revised system as a universal staging of ONFH.

Biocompatible Porous Tantalum Metal Plates in the Treatment of Tibial Fracture.

Fractures of the tibia represent a common class of injuries in orthopedics. The blood supply to the tibia is poor due to the small subcutaneous muscle tissues inside. Consequently, the tibia is prone to delayed fracture healing and nonunion of the fracture after surgery. In this case, we used porous tantalum metal plate to treat nonunion of a tibial fracture and achieved satisfactory therapeutic effects. For the first time in the field, we used 3D printing technology to fabricate porous tantalum metal plates for the treatment of tibial fractures. The resulting porous tantalum metal exhibited excellent mechanical and biological properties, and improved the therapeutic effects for the treatment of a tibial fracture nonunion. Porous tantalum metal plates have great application potential as a new implant material for internal fixation.

Micro Perfusion and Quantitative Analysis of the Femoral Head Intraosseous Artery.

The present study investigates the feasibility of micro perfusion of femoral head specimens from femoral neck fracture patients by the inferior retinacular arteries and performing intraosseous artery quantitative analysis of the femoral head. Twelve femoral neck fracture patients who had undergone conventional hip replacement surgery were included in this study. Femoral head specimen arteries were first dissected and exposed and then perfused by the inferior retinacular arteries and all the femoral heads underwent micro-CT scanning. After micro-CT scanning, a digital 3-D model was reconstructed to quantify the femoral head intraosseous arteries for comparison with a normal femoral head. The artery length density, artery volume density, and artery length/volume ratio were calculated separately and compared with normal femoral head parameters. Micro-CT scanning displayed the epiphyseal arterial network structure and their fine vascular branches in all 12 femoral neck fractures. Blood was supplied from the inferior retinacular artery to the epiphyseal arterial network then to all the fine blood vessels within the femoral head. No statistical differences were observed in femoral heads' intraosseous artery length densities or volume densities between the normal and femoral neck fracture specimens, while the artery length/volume ratio showed a statistical difference, and the ratio increased from 19 to 46. Micro perfusion of the femoral head by the inferior retinacular arteries is possible and can present the epiphyseal network and their fine arterial branches in pathologic conditions to provide a morphological basis for the study of femoral head disease.

Uncontacted tire explosion causing trauma to bilateral lower extremities: A case report.

It is uncommon for tire explosion related injuries on the lower extremity. The bilateral lower extremities were injured by tire explosion when the patient was seated in a bus. She sustained an open fracture with partial bone loss in the right calcaneus (a comminuted fracture in the right ankle joint) and a closed comminuted fracture in the left tibia and fibula. This damage was caused by uncontacted tire explosion, thanks to a thick floor between the exploded tire and the patient's feet. This type of injury on lower extremity caused by uncontacted tire explosion was uncommon.

Prevalence of Developmental Dysplasia of the Hip in Chinese Adults: A Cross-sectional Survey.

BACKGROUND: The prevalence of developmental dysplasia of the hip (DDH) is unknown in China. We aimed to determine the prevalence of DDH in Chinese adults. METHODS: In this study, we performed a cross-sectional survey of a nationally representative sample of Chinese adults. All participants underwent questionnaire investigation, physical examination, and X-ray examination. Factors associated with DDH were analyzed with logistic regression. RESULTS: We invited 29,180 individuals aged 18 years and over to participate, randomly selected from 18 primary sampling units (street districts in urban areas and townships in rural areas). The survey and examination were completed in 25,767 people (10,296 men and 15,471 women). DDH was diagnosed in 391 people, yielding an overall DDH prevalence of 1.52%. Based on this information, we estimate the number of individuals with DDH in China to be approximately 16.05 million. DDH prevalence increased with age (odds ratio = 1.53 [1.03-2.27], P = 0.036), was significantly higher among women than men (2.07% vs. 0.75%, P< 0.001), and was higher among rural residents than urban residents (1.75% vs. 1.29%, P< 0.001). Economic development was independently associated with the presence of DDH. There was no evidence of an association between body mass index alone, education, or current smoking or drinking and risk of DDH (P > 0.05). CONCLUSIONS: DDH has become an important public health problem. Special attention should be paid to residents with DDH. Screening for DDH should be performed in China.

Efficacy of N-Acetylcysteine in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

There are a number of conflicting reports describing the clinical outcomes of using N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis. We have, therefore, performed a meta-analysis to evaluate the efficacy of N-acetylcysteine, compared with control, for the treatment of idiopathic pulmonary fibrosis.Original controlled clinical trials evaluating the efficacy of N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis were included in the analysis. Searches for relevant articles were carried out in July 2014 by 2 independent researchers using PubMed, Embase, Cochrane Central, and Google Scholar. Change in forced vital capacity, change in percentage of predicted vital capacity, change in percentage of predicted carbon monoxide diffusing capacity, changes in 6 minutes walking test distance, rate of adverse events, and rate of death were expressed as outcomes using RevMan 5.0.1.Five trials, with a total of 564 patients, were included in this meta-analysis. The meta-analysis showed that the control group had significant decreases in percentage of predicted vital capacity (standardized mean difference [SMD] = 0.37; 95% confidence interval [CI]: 0.13 to -0.62; P = 0.003) and 6 minutes walking test distance (SMD = 0.25; 95% CI: 0.02-0.48; P = 0.04). There were no statistically significant differences in forced vital capacity (SMD = 0.07; 95% CI: -0.13-0.27; P = 0.52), percentage of predicted carbon monoxide diffusing capacity (SMD = 0.12; 95% CI: -0.06-0.30; P = 0.18), rates of adverse events (odd ratio = 4.50; 95% CI: 0.19-106.41; P = 0.35), or death rates (odd ratio = 1.79; 95% CI: 0.3-5.12; P = 0.28) between the N-acetylcysteine group and the control group.N-Acetylcysteine was found to have a significant effect only on decreases in percentage of predicted vital capacity and 6 minutes walking test distance. N-acetylcysteine showed no beneficial effect on changes in forced vital capacity, changes in predicted carbon monoxide diffusing capacity, rates of adverse events, or death rates.

Vascular endothelial growth factor/bone morphogenetic protein-2 bone marrow combined modification of the mesenchymal stem cells to repair the avascular necrosis of the femoral head.

Vascular endothelial cell growth factor (VEGF) combined with bone morphogenetic protein (BMP) was used to repair avascular necrosis of the femoral head, which can maintain the osteogenic phenotype of seed cells, and effectively secrete VEGF and BMP-2, and effectively promote blood vessel regeneration and contribute to formation and revascularization of tissue engineered bone tissues. To observe the therapeutic effect on the treatment of avascular necrosis of the femoral head by using bone marrow mesenchymal stem cells (BMSCs) modified by VEGF-165 and BMP-2 in vitro. The models were avascular necrosis of femoral head of rabbits on right leg. There groups were single core decompression group, core decompression + BMSCs group, core decompression + VEGF-165/BMP-2 transfect BMSCs group. Necrotic bone was cleared out under arthroscope. Arthroscopic observation demonstrated that necrotic bone was cleared out in each group, and fresh blood flowed out. Histomorphology determination showed that blood vessel number and new bone area in the repair region were significantly greater at various time points following transplantation in the core decompression + VEGF-165/BMP-2 transfect BMSCs group compared with single core decompression group and core decompression + BMSCs group (P < 0.05). These suggested that VEGF-165/BMP-2 gene transfection strengthened osteogenic effects of BMSCs, elevated number and quality of new bones and accelerated the repair of osteonecrosis of the femoral head.

Prevalence of Nontraumatic Osteonecrosis of the Femoral Head and its Associated Risk Factors in the Chinese Population: Results from a Nationally Representative Survey.

BACKGROUND: Nontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. METHODS: A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. RESULTS: NONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, χ2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, χ 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. CONCLUSIONS: Our findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.

The association between VEGF -634C/G polymorphisms and osteonecrosis of femoral head: a meta-analysis.

The polymorphism of the vascular endothelial growth factor (VEGF) -634C/G has been correlated with susceptibility to osteonecrosis of the femoral head (ONFH). The aim of this study was to derive a more precise estimation of the relationship between the VEGF -634C/G polymorphism and ONFH by performing a meta-analysis. We searched articles indexed in Pubmed, OVID and Web of Science published up to January 2015 that met our predefined criteria. The strength of the association between VEGF -634C/G polymorphism and ONFH risk was assessed by an odds ratio (OR) with the corresponding 95% CI. Three eligible studies involving 692 cases and 875 controls were identified. Overall, pooled analysis indicated a significant association between VEGF -634C/G polymorphism and ONFH risk (for C vs. G: OR=1.141, 95% CI 1.055-1.235, P=0.001; for CC vs. GG: OR=1.345, 95% CI 1.124-1.610, P=0.001; for CG vs. GG: OR=1.106, 95% CI 1.018-1.202, P=0.017; for CG+CC vs. GG: OR=1.104, 95% CI 1.035-1.177, P=0.003; for CC vs. GG+ CG: OR=1.294, 95% CI 1.051-1.593, P=0.015). No evidence of publication bias was observed. In conclusion, this meta-analysis suggested that polymorphism of VEGF -634C/G was a risk factor for ONFH. This finding needs further confirmation by trans-regional multicenter study with large sample in different ethnic populations, such as Caucasian and Austroloid.

Inhibition of UDP-Glucuronosyltransferases (UGTs) Activity by constituents of Schisandra chinensis.

Structure-activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine-Diphosphate) UDP-glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 µM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 µM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki ) to be 0.7 µM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb-drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9-mediated metabolism. In conclusion, in silico-in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis.

Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits.

Vascular hyperpermeability and highly upregulated bone resorption in the destructive repair progress of steroid-associated osteonecrosis (SAON) are associated with a high expression of VEGF and high Src activity (Src is encoded by the cellular sarcoma [c-src] gene). This study was designed to prove our hypothesis that blocking the VEGF-Src signaling pathway by specific Src siRNA is able to prevent destructive repair in a SAON rabbit model. Destructive repair in SAON was induced in rabbits. At 2, 4, and 6 weeks after SAON induction, VEGF, anti-VEGF, Src siRNA, Src siRNA+VEGF, control siRNA, and saline were introduced via intramedullary injection into proximal femora for each group, respectively. Vascularization and permeability were quantified by dynamic contrast-enhanced (DCE) MRI. At week 6 after SAON induction, proximal femurs were dissected for micro-computed tomography (µCT)-based trabecular architecture with finite element analysis (FEA), µCT-based angiography, and histological analysis. Histological evaluation revealed that VEGF enhanced destructive repair, whereas anti-VEGF prevented destructive repair and Src siRNA and Src siRNA+VEGF prevented destructive repair and enhanced reparative osteogenesis. Findings of angiography and histomorphometry were consistent with those determined by DCE MRI. Src siRNA inhibited VEGF-mediated vascular hyperpermeability but preserved VEGF-induced neovascularization. Bone resorption was enhanced in the VEGF group and inhibited in the anti-VEGF, Src siRNA, Src siRNA+VEGF groups as determined by both 3D µCT and 2D histomorphometry. FEA showed higher estimated failure load in the Src siRNA and Src siRNA+VEGF groups when compared to the vehicle control group. Blockage of VEGF-Src signaling pathway by specific Src siRNA was able to prevent steroid-associated destructive repair while improving reconstructive repair in SAON, which might become a novel therapeutic strategy.

Core decompression treatment of early-stage osteonecrosis of femoral head resulted from venous stasis or artery blood supply insufficiency.

BACKGROUND: The objective of this study was to explore the therapeutic effect of core decompression on different hemodynamics changes associated with osteonecrosis of the femoral head (ONFH). METHODS: A total of 67 patients with 76 hips suffering from ONFH (Arco stage I-IIC) received core decompression surgical procedure. Radiographic, magnetic resonance imaging, and digital subtraction angiography examinations were performed before operation. Radiographic and magnetic resonance imaging follow-ups were also performed after 12, 24, and 60 mo of operation. Clinical follow-ups were performed using the Harris Hip Score (HHS) for an average period of 5 y postoperation. RESULTS: The mean follow-up time ranged from 2-8 y with an average of 5 y. Two hips were lost during follow-up. Successful clinical efficacy (HHS ≥80) was achieved in 91.9% (68/74) of the hips. Six hips had conversion to total hip arthroplasty (THA), one hip had venous stasis, and five hips had both vein stasis and artery blood supply insufficiency. The mean HHS for the patients who did not have conversion to THA improved from 65 ± 3.5 to 89 ± 3.6 (mean ± standard deviation). Twenty-six stage I hips (100%), 22 of 23 stage IIA hips (95.7%), 13 of 15 stage IIB hips (86.7%), and 8 of 10 stage IIC hips (80%) had successful outcomes with no surgical complications. Kaplan-Meier survival analysis showed that 8-y survival rate was significantly different between stage I and stage IIC (THA as an end point; P < 0.001). CONCLUSIONS: In patients with early-stage ONFH resulted from only venous stasis, core decompression led to a significant improvement in HHS and 8-y survival rate. However, the long-term efficacy for ONFH associated with artery blood supply insufficiency was not encouraging. Therefore, preoperative digital subtraction angiography is necessary before performing core decompression.

Steroid-associated osteonecrosis: Epidemiology, pathophysiology, animal model, prevention, and potential treatments (an overview).

Steroid-associated osteonecrosis (SAON) is a common orthopaedic problem caused by administration of corticosteroids prescribed for many nonorthopaedic medical conditions. We summarised different pathophysiologies of SAON which have adverse effects on multiple systems such as bone marrow stem cells (BMSCs) pool, bone matrix, cell apoptosis, lipid metabolism, and angiogenesis. Different animal models were introduced to mimic the pathophysiology of SAON and for testing the efficacy of both prevention and treatment effects of various chemical drugs, biological, and physical therapies. According to the classification of SAON, several prevention and treatment methods are applied at the different stages of SAON. For the current period, Chinese herbs may also have the potential to prevent the occurrence of SAON. In the future, genetic analysis might also be helpful to effectively predict the development of ON and provide information for personalised prevention and treatment of patients with SAON.