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Calf deep vein thrombosis (DVT) is common in patients with hip fractures. However, studies on whether calf DVT has an impact on the prognosis are limited. This retrospective cohort study explored the association between calf DVT and 30-day and 90-day all-cause mortality in older patients with hip fractures. A total of 564 consecutive patients who underwent ultrasound examination were identified from our hip fracture database and categorized into patients with calf DVT (axial DVT, muscular DVT) and no DVT. Of these, 86 patients (15.2%) had ultrasound-confirmed calf DVT, including 66 patients with muscular DVT, and 20 patients with axial DVT. The 30-day and 90-day all-cause mortality were 2.5% and 6.0%, respectively. Multivariate Cox analysis showed that calf DVT was significantly associated with an increased risk of 30-day mortality (hazard ratio [HR] 3.21, 95% confidence interval [CI] 1.05 to 9.84, p = 0.04), but this risk relationship did not persist at 90-day follow-up (HR 1.59, 95% CI 0.69 to 3.71, p = 0.28). When calf DVT was further categorized, muscular DVT remained an independent risk factor for 30-day mortality (HR 3.95, 95% CI 1.18 to 13.15, p = 0.03), whereas this relationship was not found in axial DVT (HR 1.79, 95% CI 0.21 to 15.02, p = 0.59). In conclusion, calf DVT, especially muscular calf DVT but not axial DVT, is independently associated with an increased risk of 30-day mortality in older patients with hip fracture, but this risk relationship did not persist at 90-day follow-up.

Zhonglun Zhu,1,&ast; Zhicong Wang,1,2,&ast; Yuxuan Wu,1,&ast; Xi Chen,1 Hailong Liu,1 Jianjun Zhang,1 Mozhen Liu,2 Yuehong Liu1 1Department of Orthopedics, People’s Hospital of Deyang City, Deyang, People’s Republic of China; 2Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuehong Liu, Department of Orthopedics, People’s Hospital of Deyang City, Deyang, People’s Republic of China, Email doctorliuyuehong@163.comObjective: Widowed people have increased mortality than married people of the same age, a phenomenon known as the widowhood effect. This study aimed to investigate whether this effect exists in older patients with hip fracture.Methods: Using our own hip fracture database, a total of 1101 hip fracture patients were consecutively included from January 2014 to December 2021. Marital status was stratified as married (n = 793) and widowed (n = 308). Patients survival status was obtained from medical records or telephone follow-ups, and the outcomes were all-cause mortality at 30 days, 1 year and at latest follow-up. Univariate and multivariate Cox proportional hazard models were used to assess the association between marital status and mortality, and subgroup analyses according to sex were also conducted.Results: Compared with married patients, widowed patients were more likely to be older, female and intertrochanteric fracture, and were less likely to be urban area, smoking, drinking, and surgical treatment (P < 0.05). After a median follow-up of 37.1 months, the 30-day mortality was 4.3% (n = 47), 1-year mortality was 19.3% (n = 178), and total mortality was 34.2% (n = 376). Multivariate Cox analysis showed that widowed marital status remained an independent risk factor for 1-year mortality (HR = 1.437, 95% CI: 1.054– 1.959, P = 0.022), and total mortality (HR = 1.296, 95% CI: 1.038– 1.618, P = 0.022), whereas this association was not found in 30-day mortality (HR = 1.200, 95% CI: 0.607– 2.376, P = 0.599). Moreover, subgroup analyses also found that the widowhood effect on mortality was present in both male and female.Conclusion: Widowed marital status seems to be an independent risk factor for long-term mortality in older patients with hip fracture.Keywords: widowhood, mortality, hip fracture, older adults

Background: Osteoporosis, characterized by bone loss, usually occurs with the increased bone resorption and decreased bone formation. H2O2-induced MC3T3-E1 cells are commonly used for the study of osteoblastic activities, which play a crucial role in bone formation. Objective: This study aimed to investigate the effects of Phosphocreatine (PCr) on the osteoblastic activities in H2O2-induced MC3T3-E1 cells and elaborate on the possible molecular mechanism. Methods: The Osteoprotegerin (OPG)/Receptor Activator of NF-κB Ligand (RANKL) ratio and osteogenic markers were detected to investigate the effects of PCr on osteoblastic activities, and the osteoblastic apoptosis was detected using Hochest staining. Moreover, oxidative stress, Adenosine Triphosphate (ATP) generation and the expression of Sirtuin 1 (SIRT1), Forkhead Box O 1 (FOXO1) and Peroxisome Proliferator-Activated Receptor Γ Coactivator-1α (PGC-1α) were also examined to uncover the possible molecular mechanism in H2O2-induced MC3T3-E1 cells. Result: The results showed that PCr promoted the osteoblastic differentiation by increasing the expression levels of osteogenic markers of Alkaline Phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as increased the OPG/RANKL ratio and suppressed the osteoblastic apoptosis in H2O2-induced MC3T3-E1 cells. Moreover, treatment with PCr suppressed reactive oxygen species (ROS) over-generation and promoted the ATP production as well as increased the PGC-1α, FOXO1 and SIRT1 protein expression levels in H2O2-induced MC3T3-E1 cells. Conclusion: PCr treatment could promote osteoblastic activities via suppressing oxidative stress and increasing the ATP generation in H2O2-induced MC3T3-E1 cells. In addition, the positive effects of PCr on osteoblasts might be regulated by SIRT1/FOXO1/ PGC-1α signaling pathway.

Isopsoralen (IPRN), which comes from the fruit of Psoralea corylifolia, has been identified as a kind of phytoestrogen and has been proven to be effective for the treatment of osteoporosis (OP). However, the mechanisms underlying IPRN's anti-OP effects, especially the anti-postmenopausal osteoporosis (PMOP) effects, remain indistinct. Thus, this study aimed to investigate the effects and mechanisms of IPRN's anti-PMOP activity. In this study, the bioinformatics results predicted that IPRN could resist PMOP by targeting EGFR, AKT1, SRC, CCND1, ESR1 (ER-α), AR, PGR, BRCA1, PTGS2, and IGF1R. An ovariectomized (OVX) mice model and a H

The conventional surgical method of percutaneous pedicle screw fixation (PPSF) mainly uses X-ray fluoroscopy guidance to target the vertebral pedicle for screw placement. This study aimed to explore the feasibility of establishing a personalized drill guide template for PPSF based on a three-dimensional (3D) printing technique and to evaluate the accuracy and safety of the method for assisting screw insertion in cadaveric specimens. The T3-L3 trunk cadaveric specimens from six adults were subject to a computed tomography (CT) scan in the prone position. A three-dimensional model containing the back skin contour was reconstructed. A bilateral ideal pedicle screw in the T6-L1 segment was designed. Then, the reverse templates were designed. The two templates were fused and printed into an individualized guide template. PPSF was performed under the assistance of the guide template, and the CT scan was taken postoperatively to access the screw position. Ninety-six pedicle screws were successfully placed on the bilateral vertebral body of the T6-L1 segment with the assistance of a guide template. The guide plate was not loosened or displaced when operated by a single hand, and the operation time was 24.6 ± 7.9 s. The axial CT images after puncture indicated that in 96 puncture needles, 90 needles were grade I and 6 were grade II, with a puncture accuracy rate of 98.6%. In conclusion, an individualized PPSF navigation template was developed using Mimics software and 3D printing prototyping, which improved the accuracy of PPSF in cadaveric specimens.

Surgical site infection (SSI) in spine surgery remains a significant cause of morbidity and prolonged hospitalization. We intended to document our experience in our center and to highlight possible factors influencing SSI in posterior lumbar fusion surgery.Between June 2015 and March 2017, 448 consecutive patients with lumbar degenerative disease who underwent classic open transforaminal lumbar interbody fusion were enrolled in the study. We divided the patients into the SSI group and the non-SSI group and compared their patient-specific and procedure-specific factors. Univariate and multiple logistic regression analyses were performed to determine risk factors.There was a significant difference between groups in age (P = 0.001), body mass index (P0.001), subcutaneous fat thickness (P0.001), preoperative American Society of Anesthesiologists (ASA) score (P0.001), postoperative hemoglobin (P = 0.003), preoperative serum albumin (P0.001), operative time (P0.001), operated levels (P0.001), postoperative drainage (P = 0.004), time of draining (P0.001) and late-presenting dural tear (P = 0.008). Logistic regression analysis of these differences showed that thicker subcutaneous fat thickness, higher preoperative ASA score, lower preoperative serum albumin, and longer time of draining were significantly related to SSI (P0.05).The risk factors for SSI after lumbar fusion surgery are multifactorial. These data should provide a step toward the development of quality improvement measures aimed at reducing complications in high-risk patients. These factors may prove useful for patient counseling and for surgical planning.

Background: Isopsoralen, which comes from the fruit of the traditional Chinese medicine Psoralea corylifolia, has been identified as a kind of phytoestrogen and has been proved to be effective for the treatment of osteoporosis. However, the mechanism underlying ispsoralen’s anti-osteoporotic effects remains unknown. The purpose of this study was to study the effects and mechanisms of isopsoralen’s anti-osteoporosis activity by bioinformatics in combination with in vitro and in vivo experiments. Materials and methods: The targets and biological mechanisms of isopsoralen’s anti-osteoporotic effects were predicted by bioinformatics. Then an ovariectomized (OVX) mice model and a H2O2-induced bone marrow mesenchyml stem cell (BMSCs) model were used to detect the effects of isopsoralen on postmenopausal osteoporosis and to verify the predicted targets. Results: The results predicted that IPRN could protect against osteoporosis through several targets including EGFR, AKT1, SRC, CCND1, ESR1 (ER-α), AR, PGR, BRCA1, PTGS2, and IGF1R. In vivo and in vitro studies confirmed that isopsoralen could inhibit the bone loss induced by OVX in mice and promote the osteogenic differentiation of BMSCs damaged by H2O2 by inhibiting oxidative stress and apoptosis. Moreover, isopsoralen could significantly produce the above effects through upregulating estrogen receptors. These findings suggested that isopsoralen might be a therapeutic agent for postmenopausal osteoporosis prevention by acting as an estrogen replacement agent and a natural antioxidant. Conclusion: This study provided a comprehensive functional analysis of isopsoralen on the treatment of osteoporosis and provided a potential drug for the treatment of postmenopausal osteoporosis. Funding Information: This work was supported in part by grants from the National Natural Science Foundation of China [82073851] and Important Science Fund of Science and Technology Bureau of Liaoning Province [2020JH2/10300056]. Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: All animal studies complied the Guidelines for the Care and Use of Laboratory Animals of the National Institutes of Health and all experimental protocols in the current study were approved by the institutional animal care committee of Dalian Medical University (Dalian, China; Certificate of Conformity: No. SCXK 2018-0007).

Osteoporosis, characterized by bone loss, usually occurs with the increased bone resorption and decreased bone formation. HThis study aimed to investigate the effects of Phosphocreatine (PCr) on the osteoblastic activities in HThe Osteoprotegerin (OPG)/Receptor Activator of NF-κB Ligand (RANKL) ratio and osteogenic markers were detected to investigate the effects of PCr on osteoblastic activities, and the osteoblastic apoptosis was detected using Hochest staining. Moreover, oxidative stress, Adenosine Triphosphate (ATP) generation and the expression of Sirtuin 1 (SIRT1), Forkhead Box O 1 (FOXO1) and Peroxisome Proliferator-Activated Receptor Γ Coactivator-1α (PGC-1α) were also examined to uncover the possible molecular mechanism in HThe results showed that PCr promoted the osteoblastic differentiation by increasing the expression levels of osteogenic markers of Alkaline Phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as increased the OPG/RANKL ratio and suppressed the osteoblastic apoptosis in HPCr treatment could promote osteoblastic activities via suppressing oxidative stress and increasing the ATP generation in H

Retrospective clinical series.To investigate the clinical features and the risk factors for recurrent lumbar disc herniation (rLDH) in China.rLDH is a common cause of poor outcomes after lumbar microdiscectomy surgery. Risk factors for rLDH are increasingly being investigated. However, results in these previous studies were not always consistent.Between June 2005 and July 2012, 321 consecutive patients with single-level LDH, who underwent surgery, were enrolled in this study. We divided the patients into the recurrent group (R group) and the nonrecurrent group (N group) and compared their clinical parameters and preoperative radiologic parameters. The relationships between the variables and rLDH were evaluated by univariate analysis and multiple logistic regression analysis.There was significant difference between groups in sex (P = 0.003), age (P = 0.003), current smoking (P = 0.004), body mass index (BMI) (P = 0.04), occupational lifting (P 0.001), trauma history (P = 0.04), procedures (P = 0.04), herniation type (P = 0.006), disc height index (DUI) (P = 0.04), facet orientation (FO) (P = 0.04), facet tropism (FT) (P = 0.04), and sagittal range of motion (from) (P = 0.04). By putting these differences in logistic regression analysis, it showed that being male, young age, current smoking, higher BMI, herniation type (transligamentous extrusion), surgical procedures (bilateral laminectomy or total laminectomy), heavy works, undergoing a traumatic event, a large from, a high DUI, a large FT, and a small FO significantly related with rLDH.Based on our data, sex, age, current smoking, BMI, occupational lifting, trauma, surgical procedures, herniation type, DUI, FO, FT, and from showed a significant correlation with the incidence of rLDH. Patients with these risk factors should be paid more attention for prevention of recurrence after primary surgery.3.

Glucocorticoid-induced osteoporosis (GIO) is a secondary osteoporosis with extensive use of glucocorticoids (GCs). GCs can increase bone fragility and fracture via inhibiting osteoblastic proliferation and differentiation. Luteolin (LUT), a kind of plant flavonoid, has been reported to exhibit the antioxidant activity, but the effects of LUT on GIO still remain unclear. This study aimed to investigate the effects of LUT on GIO both in vivo and in vitro and elaborate the potential molecular mechanisms. LUT increased the superoxide dismutase activity, glutathione level and decreased reactive oxygen species (ROS) level and lactate dehydrogenase release in GIO. Meanwhile, LUT decreased caspase-3, caspase-9, and Bax protein expressions and increased Bcl-2 protein expression in GIO. LUT increased the ratio of osteoprotegerin (OPG)/receptor activator of nuclear factor-κB Ligand (RANKL) messenger RNA (mRNA) expression and mRNA expression levels of osteogenic markers, including runt-related transcription factor 2, osterix, collagen type I, and osteocalcin. LUT also enhanced the extracellular signal-regulated kinases (ERK) phosphorylation, glycogen synthase kinase 3β (GSK-3β) phosphorylation, mRNA expression levels of lipoprotein-receptor-related protein 5 (Lrp-5) and β-catenin. Further study revealed that Lrp-5 small interfering RNA (siRNA )and ERK-siRNA reduced the effects of LUT on GSK-3β phosphorylation, alkaline phosphatase (ALP) activity and the ratio of OPG/RANKL mRNA expression. Moreover, ERK-siRNA decreased Lrp-5 mRNA expression in vitro. These results indicated that LUT promoted proliferation by attenuating oxidative stress and promoted osteoblastic differentiation by regulating the ERK/Lrp-5/GSK-3β pathway in GIO. This study may bring to light the possible mechanisms involved in the action of LUT in GIO treatment, and benefit for further research on GIO.

Retrospective kinematic analysis of treated level, adjacent levels, and overall cervical spine after single-level dynamic cervical implant (DCI) stabilization versus anterior cervical discectomy and fusion (ACDF). Between June 2009 and March 2013, 70 consecutive patients with a symptomatic single-level cervical degenerative disk disease (DDD) were enrolled in this study and divided into DCI (n = 35) group and ACDF (n = 35) group. All cases were followed up for more than 5 years. The study compared perioperative parameters; clinical outcomes; and radiological parameters. Kinematic analysis included range of motion (ROM) of treated level and adjacent level, overall ROM (C2–C7), and changes in adjacent disk spaces. There were no significant differences between the DCI group and ACDF group in terms of improvement in the SF-36, VAS, NDI, and JOA scores. DCI stabilization resulted in better ROM of C2–C7 and the treated level than ACDF did. The ROM of treated level decreased significantly at 24 months after surgery and last follow-up in the DCI group, and the C2–C7 ROM showed different degrees of reduction after the 24 months after surgery. Radiological evidence of adjacent segment degeneration (ASD) at last follow-up was observed in 4/22 patients (18.2%) in the DCI group and 5/23 patients (21.7%) in the ACDF group which was not a significant difference between groups (p > 0.05). DCI stabilization for the treatment of cervical DDD cannot preserve the normal kinematics of the cervical spine for a long time, especially the treated level. DCI stabilization cannot decrease the risk of ASD compared with ACDF. These slides can be retrieved under Electronic Supplementary Material.

Alpha-lipoic acid (ALA), a naturally occurring compound and dietary supplement, has been established as a potent antioxidant that is a strong scavenger of free radicals. Recently, accumulating evidences has indicated the relationship between oxidative stress and osteoporosis (OP). Some studies have investigated the possible beneficial effects of ALA on OP both in vivo and in vitro; however, the precise mechanism(s) underlying the bone-protective action of ALA remains unclear. Considering this, we focused on the anti-oxidative capacity of ALA to exert bone-protective effects in vitro and in vivo. In the present study, the effects of ALA on osteoblastic formation in H2O2-treated MC3T3-E1 pre-osteoblasts and ovariectomy (OVX)-induced bone loss in rats were investigated. The results showed that ALA promoted osteoblast differentiation, mineralization and maturation and inhibited osteoblast apoptosis, thus increasing the OPG/receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) ratio and leading to enhanced bone formation in vitro and inhibited bone loss in vivo. Further study revealed that ALA exerted its bone-protective effects by inhibiting reactive oxygen species (ROS) generation by down-regulating Nox4 gene expression and protein synthesis and attenuating the transcriptional activation of NF-κB. In addition, ALA might exert its bone-protective effects by activating the Wnt/Lrp5/β-catenin signaling pathway. Taken together, the present study indicated that ALA promoted osteoblastic formation in H2O2-treated MC3T3-E1 cells and prevented OVX-induced bone loss in rats by regulating Nox4/ROS/NF-κB and Wnt/Lrp5/β-catenin signaling pathways, which provided possible mechanisms of bone-protective effects in regulating osteoblastic formation and preventing bone loss. Taken together, the results suggest that ALA may be a candidate for clinical OP treatment. J. Cell. Physiol. 230: 2184–2201, 2015. © 2015 Wiley Periodicals, Inc.

Recently, accumulating evidence has indicated that glucocorticoid-induced osteoporosis (GIOP) is closely related to oxidative stress and apoptosis. Alpha-lipoic acid (LA), a naturally endogenous anti-oxidant, possesses anti-oxidative and anti-apoptosis activities, implicating LA as a therapeutic agent for the treatment of GIOP. In this study, the osteogenesis-promoting effects of LA against GIOP were investigated and the mechanisms were further probed. Here, the results showed that LA inhibited oxidative stress, suppressed apoptosis and improved osteopenia by promoting the expression of osteogenesis markers, including ALP, COL-I, OCN, BMP-2, RUNX2 and OSX. Further study revealed that the osteogenesis-promoting effects of LA likely occur via the regulation of the NOX4, NF-kappaB, JNK and PI3K/AKT pathways. The present study indicated that LA may prevent GIOP and promote osteogenesis and might be a candidate for the treatment of GIOP.

High-speed counter-current chromatography (HSCCC) coupled with ultraviolet (UV) detection or evaporative light-scattering detection was successfully applied for preparative separation of five bioactive compounds from Agrimonia pilosa Ledeb. In preliminary process, D101 macroporous resin was used to separate the crude extract of the plant and four fractions (20, 40, 50, and 60% aqueous ethanol elutions) were produced. Then, these fractions were directly subjected to HSCCC purification. Five chemicals including taxifolin-3-glucoside (6.4 mg), quercetin-3-rhamnoside (13.0 mg), tiliroside (14.7 mg), agrimonolide (21.4 mg), and tormentic acid (29.8 mg) with the purities of 94.24, 95.37, 97.42, 95.29, and 96.34% were separated from each 200 mg prepared fraction. The purities were analyzed by high-performance liquid chromatography, and the chemical structures of the products were identified by UV detection, mass spectrometry, nuclear magnetic resonance, and the standards. This paper used a simple method to separate five bioactive compounds from A. pilosa Ledeb, and it could provide a new idea for the purification of bioactive compounds from other medicinal plants.

RATIONALE Foreign bodies in the vasculature usually cause numerous problems for clinical physicians. Physician experience with diagnosing and treating non-iatrogenic foreign body migration in the venous system is insufficient. PATIENT CONCERNS Here, we reported a 41-year-old male who had a foreign body in his left forearm following a work-related injury. DIAGNOSES X-ray films indicated a 3-mm high-density shadow in the superficial soft tissue of the left forearm. During the operation, the foreign body was imaged by a C-arm fluoroscope to provide a more accurate location. INTERVENTIONS The foreign body was removed completely following a microsuture of the cephalic vein. OUTCOMES The procedure was uneventful, and the patient remained asymptomatic after 6 months of clinical follow-up. LESSONS This case indicated that the foreign body in the superficial tissue needed to be accurately diagnosed and located. X-ray and C-arm fluoroscope imaging should be combined with the patient's medical history to ensure sufficient preoperative preparation.

Icariin, a traditional Chinese medicine, has previously been demonstrated to promote chondrogenesis of bone marrow mesenchymal stem cells (BMSCs) in traditional 2D cell culture. The present study investigated whether icariin has the potential to promote stable chondrogenic differentiation of BMSCs without hypertrophy in a 3D microenvironment. BMSCs were cultivated in a self‑assembling peptide nanofiber hydrogel scaffold in chondrogenic medium for 3 weeks. Icariin was added to the medium throughout the culture period at concentrations of 1x10‑6 M. Chondrogenic differentiation markers, including collagen II and SRY‑type high mobility group box 9 (SOX9) were detected by immunofluorescence, reverse transcription‑quantitative polymerase chain reaction and toluidine blue staining. Hypertrophic differentiation was further assessed by detecting collagen X and collagen I gene expression levels and alkaline phosphatase activity. The results demonstrated that icariin significantly enhanced cartilage extracellular matrix synthesis and gene expression levels of collagen II and SOX9, and additionally promoted more chondrocyte‑like rounded morphology in BMSCs. Furthermore, chondrogenic medium led to hypertrophic differentiation via upregulation of collagen X and collagen I gene expression levels and alkaline phosphatase activity, which was not potentiated by icariin. In conclusion, these results suggested that icariin treatment may promote chondrogenic differentiation of BMSCs, and inhibit the side effect of growth factor activity, thus preventing further hypertrophic differentiation. Therefore, icariin may be a potential compound for cartilage tissue engineering.

Background Dioscin, a typical steroid saponin, is isolated from Dioscorea nipponica Makino and Dioscorea zingiberensis Wright. It has estrogenic activity and many studies have also reported that dioscorea plants have an effect in preventing and treating osteoporosis. However, the molecular mechanisms underlying their effect on osteoporosis treatment are poorly understood. Therefore, the present study aims to investigate the mechanism (s) by which dioscin promotes osteoblastic proliferation and differentiation in mouse pre-osteoblast like MC3T3-E1 cells and human osteoblast-like MG-63 cells. Results We found that dioscin (0.25 μg/ml, 0.5 μg/ml, and 1.0 μg/ml) promoted MC3T3-E1 cells and MG-63 cells proliferation and differentiation dose dependently. Western blot analysis results showed that estrogen receptor α (ER-α), estrogen receptor β (ER-β), β-catenin and Bcl-2 protein expression increased after MC3T3-E1 cells were treated with dioscin. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that dioscin could increase the ratio of osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) and up-regulate the level of Lrp5 and β-catenin. And by RNA interference analysis, we proved that the effect of dioscin increasing the ratio of OPG/RANKL was dependent on Lrp5 pathway. In addition, we also found that these effects of dioscin were abolished by ICI 182, 780 (100 nM), an antagonist of ER, indicating that an ER signaling pathway was also involved. We also found that dioscin (0.25 μg/ml, 0.5 μg/ml, and 1.0 μg/ml) induced MG-63 cells proliferation and differentiation in a dose-dependent manner. Western blot analysis results indicated that ER-α, ER-β and β-catenin protein expression increased after MG-63 cells were treated with dioscin. Conclusions The current study is the first to reveal that dioscin can promote osteoblasts proliferation and differentiation via Lrp5 and ER pathway.

In a recent meta-analysis by Laudy et al ,1 the authors used a fixed-effects model when there was significant heterogeneity for Western Ontario and McMaster Universities Osteoarthritis (WOMAC) knee pain (refer to figure 11 of the article, χ2=17.12, I2=94%, p

High-speed counter-current chromatography (HSCCC) coupled with ultraviolet (UV) detection or evaporative light-scattering detection was successfully applied for preparative separation of five bioactive compounds from Agrimonia pilosa Ledeb. In preliminary process, D101 macroporous resin was used to separate the crude extract of the plant and four fractions (20, 40, 50, and 60% aqueous ethanol elutions) were produced. Then, these fractions were directly subjected to HSCCC purification. Five chemicals including taxifolin-3-glucoside (6.4 mg), quercetin-3-rhamnoside (13.0 mg), tiliroside (14.7 mg), agrimonolide (21.4 mg), and tormentic acid (29.8 mg) with the purities of 94.24, 95.37, 97.42, 95.29, and 96.34% were separated from each 200 mg prepared fraction. The purities were analyzed by high-performance liquid chromatography, and the chemical structures of the products were identified by UV detection, mass spectrometry, nuclear magnetic resonance, and the standards. This paper used a simple method to separate five bioactive compounds from A. pilosa Ledeb, and it could provide a new idea for the purification of bioactive compounds from other medicinal plants.

Objective Increased enzymatic activity of matrix metalloproteinases (MMPs) may promote the progression of rheumatoid arthritis (RA). We undertook this study to investigate the expression and localization of human macrophage elastase (MMP-12) in synovial tissue from RA patients and to compare MMP-12 levels in the synovial tissue and synovial fluid of RA patients with the corresponding levels in patients with osteoarthritis (OA). Methods We obtained synovial tissues from 23 RA patients and 29 OA patients and analyzed MMP-12 expression using immunohistochemistry, Western and Northern blotting analyses, and zymography. Furthermore, we quantified MMP-12 levels in synovial fluid by Western blotting and zymography. Results Northern blotting analysis demonstrated that RA synovial tissue contained higher levels of MMP-12 messenger RNA than did OA synovial tissue. Western blotting revealed that MMP-12 proteins were consistently and markedly increased in RA synovial tissue compared with OA synovial tissue. A greater amount of immunoreactive proteins corresponding to catalytic forms of MMP-12 was present in RA synovial tissue and synovial fluid, and the MMP-12 proteins exhibited caseinolytic activity in vitro. Immunohistochemical staining showed that the major cells expressing MMP-12 were synovial lining cells, many of which were inflammatory macrophages. Conclusion These results establish a possible mechanism by which macrophage-derived MMP-12 may play an important role in the destructive process in RA. Inhibition of MMP-12 may be a potential modality for the treatment of RA.