On the way to the azygos vein: a road of return rather than ruined.

BACKGROUND: The malposition of central venous catheters (CVCs) may lead to vascular damage, perforation, and even mediastinal injury. The malposition of CVC from the right subclavian vein into the azygos vein is extremely rare. Here, we report a patient with CVC malposition into the azygos vein via the right subclavian vein. We conduct a comprehensive review of the anatomical structure of the azygos vein and the manifestations associated with azygos vein malposition. Additionally, we explore the resolution of repositioning the catheter into the superior vena cava by carefully withdrawing a specific length of the catheter. CASE PRESENTATION: A 79-year-old female presented to our department with symptoms of complete intestinal obstruction. A double-lumen CVC was inserted via the right subclavian vein to facilitate total parenteral nutrition. Due to the slow onset of sedative medications during surgery, the anesthetist erroneously believed that the CVC had penetrated the superior vena cava, leading to the premature removal of the CVC. Postoperative contrast-enhanced computed tomography of the chest confirmed that the central venous catheter had not penetrated the superior vena cava but malpositioned into the azygos vein. The patient was discharged 15 days after surgery without any complications. CONCLUSIONS: CVC malposition into the azygos vein is extremely rare. Clinical practitioners should be vigilant regarding this form of catheter misplacement. Ensuring the accurate positioning of the CVC before each infusion is crucial. Utilizing chest X-rays in both frontal and lateral views, as well as chest computed tomography, can aid in confirming the presence of catheter misplacement.

ACETYL-COA PRODUCTION BY OCTANOIC ACID ALLEVIATES ACUTE COMPARTMENT SYNDROME-INDUCED SKELETAL MUSCLE INJURY THROUGH REGULATING MITOPHAGY.

ABSTRACT: Background: Treatment of acute compartment syndrome (ACS)-induced skeletal muscle injury remains a challenge. Previous studies have shown that octanoic acid is a promising treatment for ACS owing to its potential ability to regulate metabolic/epigenetic pathways in ischemic injury. The present study was designed to investigate the efficacy and underlying mechanism of octanoic acid in ACS-induced skeletal muscle injury. Methods: In this study, we established a saline infusion ACS rat model. Subsequently, we assessed the protective effects of sodium octanoate (NaO, sodium salt of octanoic acid) on ACS-induced skeletal muscle injury. Afterward, the level of acetyl-coenzyme A and histone acetylation in the skeletal muscle tissue were quantified. Moreover, we investigated the activation of the AMP-activated protein kinas pathway and the occurrence of mitophagy in the skeletal muscle tissue. Lastly, we scrutinized the expression of proteins associated with mitochondrial dynamics in the skeletal muscle tissue. Results: The administration of NaO attenuated muscle inflammation, alleviating oxidative stress and muscle edema. Moreover, NaO treatment enhanced muscle blood perfusion, leading to the inhibition of apoptosis-related skeletal muscle cell death after ACS. In addition, NaO demonstrated the ability to halt skeletal muscle fibrosis and enhance the functional recovery of muscle post-ACS. Further analysis indicates that NaO treatment increases the acetyl-CoA level in muscle and the process of histone acetylation by acetyl-CoA. Lastly, we found NaO treatment exerts a stimulatory impact on the activation of the AMPK pathway, thus promoting mitophagy and improving mitochondrial dynamics. Conclusion: Our findings indicate that octanoic acid may ameliorate skeletal muscle injury induced by ACS. Its protective effects may be attributed to the promotion of acetyl-CoA synthesis and histone acetylation within the muscular tissue, as well as its activation of the AMPK-related mitophagy pathway.

Sodium octanoate alleviates cardiac and cerebral injury after traumatic cardiac arrest in a porcine model.

INTRODUCTION: Traumatic cardiac arrest (TCA) is a severe condition with a high mortality rate, and patients who survive from TCA face a poor prognosis due to post-resuscitation injury, including cardiac and cerebral injury, which remains a serious challenge. Sodium octanoate has shown protective effects against various diseases. The present study aims to investigate sodium octanoate's protective effects against cardiac and cerebral injury after TCA in a porcine model. METHODS: The study included a total of 22 male domestic pigs divided into three groups: Sham group (n = 7), TCA group (n = 7), and sodium octanoate (SO) group (n = 8). Hemorrhage was initiated via the right femoral artery by a blood pump at a rate of 2 ml·kg-1·min-1 to establish TCA model. The Sham group underwent only endotracheal intubation and arteriovenous catheterization, without experiencing the blood loss/cardiac arrest/resuscitation model. At 5 min after resuscitation, the SO group received a continuous sodium octanoate infusion while the TCA group received the same volume of saline. General indicators were monitored, and blood samples were collected at baseline and at different time points after resuscitation. At 24 h after resuscitation, pigs were sacrificed, and heart and brain were obtained for cell apoptosis detection, iron deposition staining, oxidative stress detection, and the expression of ferroptosis-related proteins (ACSL4 and GPX4). RESULTS: Sodium octanoate significantly improved mean arterial pressure, cardiac output and ejection fraction induced by TCA. Serum biomarkers of cardiac and cerebral injury were found to increase at all time points after resuscitation, while sodium octanoate significantly reduced their levels. The apoptosis rates of cardiomyocytes and cerebral cortex cells in the SO group were significantly lower than in the TCA group, along with a reduced area of iron deposition staining. The sodium octanoate also reduced oxidative stress and down-regulated ferroptosis which was indicated by protein level alteration of ACSL4 and GPX4. CONCLUSION: Our study's findings suggest that early infusion of sodium octanoate significantly alleviates post-resuscitation cardiac and cerebral injury in a porcine model of TCA, possibly through inhibition of cell apoptosis and GPX4-mediated ferroptosis. Therefore, sodium octanoate could be a potential therapeutic strategy for patients with TCA.

MFG-E8 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells through GSK3ß/ß-catenin signaling pathway.

Fracture nonunion and bone defects are challenging for orthopedic surgeons. Milk fat globule-epidermal growth factor 8 (MFG-E8), a glycoprotein possibly secreted by macrophages in a fracture hematoma, participates in bone development. However, the role of MFG-E8 in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. We investigated the osteogenic effect of MFG-E8 in vitro and in vivo. The CCK-8 assay was used to assess the effect of recombinant human MFG-E8 (rhMFG-E8) on the viability of hBMSCs. Osteogenesis was investigated using RT-PCR, Western blotting, and immunofluorescence. Alkaline phosphatase (ALP) and Alizarin red staining were used to evaluate ALP activity and mineralization, respectively. An enzyme-linked immunosorbent assay was conducted to evaluate the secretory MFG-E8 concentration. Knockdown and overexpression of MFG-E8 in hBMSCs were established via siRNA and lentivirus vector transfection, respectively. Exogenous rhMFG-E8 was used to verify the in vivo therapeutic effect in a tibia bone defect model based on radiographic analysis and histological evaluation. Endogenous and secretory MFG-E8 levels increased significantly during the early osteogenic differentiation of hBMSCs. Knockdown of MFG-E8 inhibited the osteogenic differentiation of hBMSCs. Overexpression of MFG-E8 and rhMFG-E8 protein increased the expression of osteogenesis-related genes and proteins and enhanced calcium deposition. The active ß-catenin to total ß-catenin ratio and the p-GSK3ß protein level were increased by MFG-E8. The MFG-E8-induced enhanced osteogenic differentiation of hBMSCs was partially attenuated by a GSK3ß/ß-catenin signaling inhibitor. Recombinant MFG-E8 accelerated bone healing in a rat tibial-defect model. In conclusion, MFG-E8 promotes the osteogenic differentiation of hBMSCs by regulating the GSK3ß/ß-catenin signaling pathway and so, is a potential therapeutic target.

Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy.

Mec1 is a DNA damage sensor, which performs an essential role in the DNA damage response pathway and glucose starvation-induced autophagy. However, the functions of Mec1 in autophagy remain unclear. In response to glucose starvation, Mec1 forms puncta, which are recruited to mitochondria through the adaptor protein Ggc1. Here, we show that Mec1 puncta also contact the phagophore assembly site (PAS) via direct binding with Atg13. Functional analysis of the Atg13-Mec1 interaction revealed two previously unrecognized protein regions, the Mec1-Binding Region (MBR) on Atg13 and the Atg13-Binding Region (ABR) on Mec1, which mediate their mutual association under glucose starvation conditions. Disruption of the MBR or ABR impairs the recruitment of Mec1 puncta and Atg13 to the PAS, consequently blocking glucose starvation-induced autophagy. Additionally, the MBR and ABR regions are also crucial for DNA damage-induced autophagy. We thus propose that Mec1 regulates glucose starvation-induced autophagy by controlling Atg13 recruitment to the PAS.

Broadband Insulator-Based Dynamic Diode with Ultrafast Hot Carriers Process.

The excitation, rebound, and transport process of hot carriers (HCs) inside dynamic diode (DD) based on insulators has been rarely explored due to the original stereotyped in which it was thought that the insulators are nonconductive. However, the carrier dynamics of DD is totally different from the static diode, which may bring a subverting insight of insulators. Herein, we discovered insulators could be conductive under the framework of DD; the HC process inside the rebounding procedure caused by the disappearance and reestablishment of the built-in electric field at the interface of insulator/semiconductor heterostructure is the main generation mechanism. This type of DD can response fast up to 1 µs to mechanical excitation with an output of ~10 V, showing a wide band frequency response under different input frequencies from 0 to 40 kHz. It can work under extreme environments; various applications like underwater communication network, self-powered sensor/detector in the sea environment, and life health monitoring can be achieved.

Clinical effectiveness of a pneumatic compression device combined with low-molecular-weight heparin for the prevention of deep vein thrombosis in trauma patients: A single-center retrospective cohort study.

BACKGROUND: To investigate the clinical effectiveness of a pneumatic compression device (PCD) combined with low-molecular-weight heparin (LMWH) for the prevention and treatment of deep vein thrombosis (DVT) in trauma patients. METHODS: This study retrospectively analyzed 286 patients with mild craniocerebral injury and clavicular fractures admitted to our department from January 2016 to February 2020. Patients treated with only LMWH served as the control group, and patients treated with a PCD combined with LMWH as the observation group. The incidence of DVT, postoperative changes in the visual analogue scale (VAS) score, and coagulation function were observed and compared between the two groups. Excluding the influence of other single factors, binary logistic regression analysis was used to evaluate the use of a PCD in the patient's postoperative coagulation function. RESULTS: After excluding 34 patients who did not meet the inclusion criteria, 252 patients were were included. The incidence of DVT in the observation group was significantly lower than that in the control group (5.6% vs. 15.1%, χ2=4.605, P<0.05). The postoperative VAS scores of the two groups were lower than those before surgery (P<0.05). The coagulation function of the observation group was significantly higher than that of the control group, with a better combined anticoagulant effect (P<0.05). There were no significant differences between the two groups in preoperative or postoperative Glasgow Coma Scale scores, intraoperative blood loss, postoperative infection rate, or length of hospital stay (P>0.05). According to logistic regression analysis, the postoperative risk of DVT in patients who received LMWH alone was 1.764 times that of patients who received LMWH+PCD (P<0.05). The area under the receiver operating characteristic (AUROC) curve of partial thromboplastin time (APTT) and platelet (PLT) were greater than 0.5, indicating that they were the influence indicators of adding PCD to prevent DVT. Excluding the influence of other variables, LMWH+PCD effectively improved the coagulation function of patients. CONCLUSIONS: Compared with LMWH alone, LMWH+PCD could improve blood rheology and coagulation function in patients with traumatic brain injury and clavicular fracture, reduce the incidence of DVT, shorten the length of hospital stay, and improve the clinical effectiveness of treatment.

Low-dose IL-34 has no effect on osteoclastogenesis but promotes osteogenesis of hBMSCs partly via activation of the PI3K/AKT and ERK signaling pathways.

BACKGROUND: Inflammatory microenvironment is significant to the differentiation and function of mesenchymal stem cells (MSCs). It evidentially influences the osteoblastogenesis of MSCs. IL-34, a newly discovered cytokine, playing a key role in metabolism. However, the research on its functional role in the osteogenesis of MSCs was rarely reported. Here, we described the regulatory effects of low-dose IL-34 on both osteoblastogenesis and osteoclastogenesis. METHODS: We performed the osteogenic effects of hBMSCs by exogenous and overexpressed IL-34 in vitro, so were the osteoclastogenesis effects of mBMMs by extracellular IL-34. CCK-8 was used to assess the effect of IL-34 on the viability of hBMSCs and mBMMs. ALP, ARS, and TRAP staining was used to evaluate ALP activity, mineral deposition, and osteoclastogenesis, respectively. qRT-PCR and Western blotting analysis were performed to detect the expression of target genes and proteins. ELISA was used to evaluate the concentrations of IL-34. In vivo, a rat tibial osteotomy model and an OVX model were established. Radiographic analysis and histological evaluation were performed to confirm the therapeutic effects of IL-34 in fracture healing and osteoporosis. Statistical differences were evaluated by two-tailed Student's t test, one-way ANOVA with Bonferroni's post hoc test, and two-way ANOVA with Bonferroni multiple comparisons post hoc test in the comparison of 2 groups, more than 2 groups, and different time points of treated groups, respectively. RESULTS: Promoted osteoblastogenesis of hBMSCs was observed after treated by exogenous or overexpressed IL-34 in vitro, confirmed by increased mineral deposits and ALP activity. Furthermore, exogenous or overexpressed IL-34 enhanced the expression of p-AKT and p-ERK. The specific AKT and ERK signaling pathway inhibitors suppressed the enhancement of osteoblastogenesis induced by IL-34. In a rat tibial osteotomy model, imaging and histological analyses testified the local injection of exogenous IL-34 improved bone healing. However, the additional IL-34 has no influence on both osteoclastogenesis of mBMMs in vitro and osteoporosis of OVX model of rat in vivo. CONCLUSIONS: Collectively, our study demonstrate that low-dose IL-34 regulates osteogenesis of hBMSCs partly via the PIK/AKT and ERK signaling pathway and enhances fracture healing, with neither promoting nor preventing osteoclastogenesis in vitro and osteoporosis in vivo.

Metabolomic Analysis Reveals That the Mechanism of Astaxanthin Improves the Osteogenic Differentiation Potential in Bone Marrow Mesenchymal Stem Cells.

At present, little research has been done on the metabolic phenotype of the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. In this study, the effect of astaxanthin on improving osteogenic differentiation potential of mesenchymal stem cells was studied by metabolomics. Results showed that L-methionine, L-tyrosine, and 2-hydroxycinnamic acid were upregulated in MSCs treated with astaxanthin, while L-lysine, L-pipecolic acid, L-histidine, L-arginine, D-fructose, and L-aspartic acid were downregulated in samples treated with astaxanthin. In addition, astaxanthin exhibited a significant dose-dependent relationship with these markers. Metabolic pathway enrichment analysis revealed that AST mainly regulated phenylalanine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; and pantothenate and CoA biosynthesis during the process of osteogenic differentiation of MSCs. Furthermore, the staining results showed that astaxanthin could actively promote the osteogenic differentiation of mesenchymal stem cells. These findings clearly indicate that astaxanthin plays an important role in inducing osteogenic differentiation of mesenchymal stem cells. In addition, the changed metabolites can be used to monitor the differentiation process.

Intra-Articular Steroid Injection for Patients with Hip Osteoarthritis: A Systematic Review and Meta-Analysis.

PURPOSE: The aim of this current review was to confirm the efficacy of intra-articular steroid therapy (IAST) for patients with hip osteoarthritis (OA) and discuss the duration and influential factors of IAST. METHODS: Online databases (Medline, EMBASE, and Web of Science) were searched from inception to May 2019. Both randomized controlled trials (RCTs) and noncontrolled trials assessing the efficacy of hip IAST on pain were included. Common demographics data were extracted using a standardized form. Quality was assessed on the basis of Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. RESULTS: 12 trials met the inclusion criteria. According to data from individual trials, IAST had significant efficacy on hip OA in both immediate and delay pain reduction, which persisted up to 12 weeks after IAST. The influences of the baseline severity of hip OA or synovitis and injection dose or volume on the clinical outcome of IAST were still controversial. The IAST appeared to be well tolerant by most of the participants. CONCLUSION: IAST was proved to be an efficacious therapy in both immediate and delay pain reduction for hip OA patients within 12 weeks. The longer follow-up data of efficacy and safety and potentially influential factors are still unclear and needed further confirmation.

Atg11 is required for initiation of glucose starvation-induced autophagy.

How energy deprivation induces macroautophagy/autophagy is not fully understood. Here, we show that Atg11, a receptor protein for cargo recognition in selective autophagy, is required for the initiation of glucose starvation-induced autophagy. Upon glucose starvation, Atg11 facilitates the interaction between Snf1 and Atg1, thus is required for Snf1-dependent Atg1 activation. Phagophore assembly site (PAS) formation requires Atg11 via its control of the association of Atg17 with Atg29-Atg31. The binding of Atg11 with Atg9 is crucial for recruiting Atg9 vesicles to the PAS and, thus, glucose starvation-induced autophagy. We propose Atg11 as a key initiation factor controlling multiple key steps in energy deprivation-induced autophagy. Abbreviations: AMPK: AMP-activated protein kinase; Ams1: α-mannosidase; Ape1: aminopeptidase I; Cvt: cytoplasm-to-vacuole targeting; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; GFP: green fluorescent protein; MBP: myelin basic protein; MMS: methanesulfonate; PAS: phagophore assembly site; PNBM: p-nitrobenzyl mesylate; SD-G: glucose starvation medium; SD-N: nitrogen starvation medium; ULK1, unc-51 like autophagy activating kinase 1; WT: wild type.

Immunomodulatory properties of graphene oxide for osteogenesis and angiogenesis.

BACKGROUND: The osteo-immunomodulatory properties of biomaterials play an important role in the outcomes of bone regeneration. Graphene oxide (GO) has been widely applied in many research fields due to its unique properties. However, the immunomodulatory properties of GO as a biomaterial for bone tissue engineering are still unclear. MATERIALS AND METHODS: In this study, we evaluated the Inflammatory response of RAW264.7 cells influenced by GO. Then the osteogenic differentiation of BMSCs, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) by stimulation with GO/RAW 264.7-conditioned culture medium were accessed. We also further investi gated the possible mechanisms underlying the osteo- and angio-immunomodulatory effects of GO. RESULTS: Our results showed that GO stimulates the secretion of oncostatin M, tumor necrosis factor alpha and other factors through the nuclear factor-κB pathway. GO/RAW264.7-conditioned medium promoted the osteogenic differentiation of BMSCs, stimulated upregulation of the HUVECs of vascular-related receptors, and promoted their tube formation in vitro. CONCLUSION: In conclusion, our research shows that GO, as a biomaterial, can induce the formation of a beneficial osteo-immunomodulatory environment and is a promising biomaterial for bone tissue engineering.

Comparison of core decompression and conservative treatment for avascular necrosis of femoral head at early stage: a meta-analysis.

The purpose of the current meta-analysis was to compare the efficacy of core decompression (CD) and conservative treatment (CT) for saving femoral heads in patients with avascular necrosis of femoral head (ANFH). Four RCTs and two CCTs involving 323 hips with 24- to 48-months follow-up were included in this review. Our results suggested CD had a trend of favorable results in contrast to other CT (OR 3.28; 95% CI 0.77-14.02; P = 0.11) but saved much less hips compared to biophysical treatments [odds ratio (OR) 0.37; 95% CI 0.18-0.74; P = 0.005]. In the stratified survival rate analysis by ANFH stage, interestingly, CD group got a significantly higher successful rate of hip joint conservation than other CT group in both stage I and stage II-III (stage I: OR 4.43; 95% CI 1.34-14.65; P = 0.01; stage II-III: OR 6.75; 95% CI 2.18-20.90; P = 0.0009). In the biophysical stimulation subgroup, however, an even higher frequency of survived hips were observed compared to CD group at stage II-III (CD vs. biophysical stimulation: OR 0.34; 95% CI 0.17-0.67; P = 0.002). In conclusion, performing CD for ANFH is effective for preventing femoral collapse within a short-term follow-up, but an even higher successful rate were expected by biophysical stimulations. Nevertheless, the short-term follow-up, the small sample size of the current meta-analysis only provide limited quality of evidence, which required confirmation from further large-scale, well-designed RCT with longer follow-up.

Intrathoracic dislocation of the humeral head accompanied by polytrauma: How to treat it?

High-energy trauma to the shoulder is associated with multiple injuries and is often difficult to evaluate. One of these complex traumas is the displacement of the humeral head into the thoracic cavity. This study aimed to report a patient who presented after falling three floors. Initially, the patient underwent chest drainage and thoracoscopy to remove the displaced humeral head and, subsequently, underwent delayed artificial humeral head replacement. Hemodynamic stability, systematic evaluation, removal of the humeral head, and individual shoulder reconstruction are recommended for these patients.

Effects of antimicrobial peptides on Staphylococcus aureus growth and biofilm formation in vitro following isolation from implant-associated infections.

To prevent biomaterial-associated infections, antibiotic agents are recommended for various medical conditions requiring biomaterial implants, but resistance often appears after the introduction of antibiotics into clinical use. Therefore, new strategies for the prevention or treatment for biomaterial-associated infections are required. The purpose of this study was to evaluate the effects of antimicrobial peptides on growth and biofilm formation of Staphylococcus aureus isolated from implant-associated infections. A total of 20 patients with culture-proven staphylococcal infection associated with stable orthopedic implants were selected as the experimental group. S. aureus were isolated from tissue biopsies for identification, the isolated strains were mixed with Tet213 incubated at 37°C and viable bactrial number of S. aureus was counted. For the biofilm formation, the broad spectrum AMP Tet213 was selected and loaded onto the Ti coating first. At the same time Ti coated with Tet213 were mixed with S. aureus in vitro to form biofilm. After 30 min, 2 h, 4 h, 6 h, 8 h, the population of S. aureus in the biofilm was counted. Tet213 showed significant antibacterial effect on 16 strains (P < 0.05, Table 1). The inhibition rate reached above 80% among 12 strains of the clinically isolated strain. In biofilm experiments, counts of the NO. 1, 2, 3, 4 strains in biofilms decreased significantly after 2 h (P < 0.05), while there was no obvious difference in counts of NO. 5 strain (P > 0.05). The broad spectrum AMP Tet213 could strongly reduce the growth and biofilm formation of S. aureus in vitro, and the use of this might be an important new approach to target implant-associated infections.

Use of a tourniquet in total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: A tourniquet is commonly used in total knee arthroplasty (TKA). However, the effectiveness and safety of tourniquets are debated. We performed this study to investigate whether patients benefit from the use of tourniquets in TKA. METHODS: The literature search was conducted using PubMed, Cochrane Library, MEDLINE, Embase, and other medical databases. After a literature search, 26 randomized controlled trials involving 1,450 knees were analyzed. RESULTS: Tourniquet use significantly decreased intraoperative blood loss, transfusion rate, and operation time but not postoperative blood loss, measurable total blood loss, calculated total blood loss, transfusion volume, incidence of pulmonary embolism, or duration of hospital stay. It also slowed down joint functional recovery in the short term and increased the incidence of deep vein thrombosis and other minor wound complications. CONCLUSIONS: Data from this meta-analysis indicate that patients may benefit from the use of a tourniquet in TKA; however, it use is accompanied by disadvantages and complications. Because of the very low-evidence quality and lower grading of recommendations, assessment, development, and evaluation recommendation strength, no guidelines can be developed based on current evidence.

Efficacy of alendronate for preventing collapse of femoral head in adult patients with nontraumatic osteonecrosis.

The purpose of the current review was to determine the efficacy of alendronate for preventing collapse of femoral head in adult patients with nontraumatic avascular osteonecrosis of femoral head (ANFH). Five randomized controlled trials (RCTs) involving 305 hips were included in this review, of which 3 studies investigated alendronate versus control/placebo and the other 2 studies compared the combination of alendronate and extracorporeal shockwave therapy (ESWT) with ESWT alone. Our results suggested that even the patients with extensive necrosis encountered much less collapse in the alendronate group than control group. In these RCTs, their data also indicated a positive short- and middle-term efficacy of alendronate treatment in joint function improvement and hip pain diminishment. With the presence of the outlier study, only insignificant overall efficacy of alendronate could be observed with substantial heterogeneities. In addition, we did not find any additive benefits of alendronate in combination with ESWT for preventing collapse compared to ESWT alone. In conclusion, there is still lack of strong evidence for supporting application of alendronate in adult patients with nontraumatic ANFH, which justified that large scale, randomized, and double-blind studies should be developed to demonstrate the confirmed efficacies, detailed indication, and optimized strategy of alendronate treatment.

Protective effects of biochanin A on articular cartilage: in vitro and in vivo studies.

BACKGROUND: Increased production of matrix metalloproteinases (MMPs) is closely related to the progression of osteoarthritis (OA). The present study was performed to investigate the potential value of biochanin A in inhibition of MMP expression in both rabbit chondrocytes and an animal model of OA. METHODS: MTT assay was performed to assess chondrocyte survival in monolayers. The mRNA and protein expression of MMPs (including MMP-1, MMP-3, and MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in interleukin-1 < beta > (IL-1ß)-induced rabbit chondrocytes were determined by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The involvement of the NF-kappaB (NF-κB) pathway activated by IL-1ß was determined by western blotting. The in vivo effects of biochanin A were evaluated by intra-articular injection in an experimental OA rabbit model induced by anterior cruciate ligament transection (ACLT). RESULTS: Biochanin A downregulated the expression of MMPs and upregulated TIMP-1 at both the mRNA and protein levels in IL-1ß-induced chondrocytes in a dose-dependent manner. In addition, IL-1ß-induced activation of NF-κB was attenuated by biochanin A, as determined by western blotting. Moreover, biochanin A decreased cartilage degradation as determined by both morphological and histological analyses in vivo. CONCLUSIONS: Taken together, these findings suggest that biochanin A may be a useful agent in the treatment and prevention of OA.