Huiwu Li

Magnesium and the Risk of Cardiovascular Events: A Meta-Analysis of Prospective Cohort Studies

Background Prospective studies that have examined the association between dietary magnesium intake and serum magnesium concentrations and the risk of cardiovascular disease (CVD) events have reported conflicting findings. We undertook a meta-analysis to evaluate the association between dietary magnesium intake and serum magnesium concentrations and the risk of total CVD events. Methodology/Principal Findings We performed systematic searches on MEDLINE, EMBASE, and OVID up to February 1, 2012 without limits. Categorical, linear, and nonlinear, dose-response, heterogeneity, publication bias, subgroup, and meta-regression analysis were performed. The analysis included 532,979 participants from 19 studies (11 studies on dietary magnesium intake, 6 studies on serum magnesium concentrations, and 2 studies on both) with 19,926 CVD events. The pooled relative risks of total CVD events for the highest vs. lowest category of dietary magnesium intake and serum magnesium concentrations were 0.85 (95% confidence interval 0.78 to 0.92) and 0.77 (0.66 to 0.87), respectively. In linear dose-response analysis, only serum magnesium concentrations ranging from 1.44 to 1.8 mEq/L were significantly associated with total CVD events risk (0.91, 0.85 to 0.97) per 0.1 mEq/L (Pnonlinearity = 0.465). However, significant inverse associations emerged in nonlinear models for dietary magnesium intake (Pnonlinearity = 0.024). The greatest risk reduction occurred when intake increased from 150 to 400 mg/d. There was no evidence of publication bias. Conclusions/Significance There is a statistically significant nonlinear inverse association between dietary magnesium intake and total CVD events risk. Serum magnesium concentrations are linearly and inversely associated with the risk of total CVD events.

The promotion of cartilage defect repair using adenovirus mediated Sox9 gene transfer of rabbit bone marrow mesenchymal stem cells

Although Sox9 is essential for chondrogenic differentiation and matrix production, its application in cartilage tissue engineering has been rarely reported. In this study, the chondrogenic effect of Sox9 on bone marrow mesenchymal stem cells (BMSCs) in vitro and its application in articular cartilage repair in vivo were evaluated. Rabbit BMSCs were transduced with adenoviral vector containing Sox9. Toluidine blue, safranin O staining and real-time PCR were performed to check chondrogenic differentiation. The results showed that Sox9 could induce chondrogenesis of BMSCs both in monolayer and on PGA scaffold effectively. The rabbit model with full-thickness cartilage defects was established and then repaired by PGA scaffold and rabbit BMSCs with or without Sox9 transduction. HE, safranin O staining and immunohistochemistry were used to assess the repair of defects by the complex. Better repair, including more newly-formed cartilage tissue and hyaline cartilage-specific extracellular matrix and greater expression of several chondrogenesis marker genes were observed in PGA scaffold and BMSCs with Sox9 transduction, compared to that without transduction. Our findings defined the important role of Sox9 in the repair of cartilage defects in vivo and provided evidence that Sox9 had the potential and advantage in the application of tissue engineering.

Inhibition of the Wnt-β-catenin and Notch signaling pathways sensitizes osteosarcoma cells to chemotherapy

Osteosarcoma (OS) is one of the most common malignant bone tumors in early adolescence. Multi-drug chemotherapy has greatly increased the five year survival rate from 20% to 70%. However, the rate has been staggering for 30 years and the prognosis is particularly poor for patients with recurrence and metastasis. Our study aimed to investigate the role of Wnt-β-catenin, Notch and Hedgehog pathway in OS development because all these pathways are involved in skeletal development, tumorigenesis and chemoresistance. Our results showed that the major components in Wnt-β-catenin pathway, e.g. Wnt3a, β-catenin and Lef1, were consistently upregulated in human osteosarcoma cell line Saos2 cells compared to human fetal osteoblasts (hFOB), whereas the changes in the expression levels of Notch and Hh signaling molecules were not consistent. Knocking down β-catenin increased the Saos2 sensitivity to methotrexate (MTX) induced cell death. Consistently, the expression level of β-catenin protein correlated with the invasiveness of OS, as evidenced by more intensive β-catenin immunoreactivity in higher grade OS samples. Chemical inhibition of the Wnt-β-catenin signaling enhanced MTX mediated death of Saos2 cells. A synergistic effect with MTX was observed when both inhibitors for Wnt-β-catenin and Notch pathways were simultaneously used, while the addition of the Hh inhibitor did not further improve the efficacy. Our findings provide some novel insight to OS pathogenesis and lay a foundation for future application of Wnt-β-catenin and Notch inhibitors together with the currently used chemotherapeutic drugs to improve the outcome of OS treatment.

Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo.

Osteoclasts play a pivotal role in diseases such as osteoporosis, rheumatoid arthritis and tumour bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast‐related diseases. Here, we examined changes in osteoclastogenesis and LPS‐induced osteolysis in response to andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata.

Meta-Analysis of Sonication Fluid Samples from Prosthetic Components for Diagnosis of Infection after Total Joint Arthroplasty

ABSTRACT This meta-analysis included 12 studies that evaluated sonication fluid cultures (SFC) for the diagnosis of prosthetic joint infection (PJI). The pooled sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.74 to 0.84) and 0.95 (CI, 0.90 to 0.98), respectively. Subgroup analyses showed that a 14-day anaerobic culture may improve sensitivity, the use of centrifugation or vortexing may improve specificity, and the use of 400 to 500 ml of Ringers solution for containers may improve sensitivity and specificity. The best SFC cutoff was ≥5 CFU. In conclusion, SFC has high sensitivity and very high specificity for diagnosing PJI.

Continuous cyclic mechanical tension inhibited Runx2 expression in mesenchymal stem cells through RhoA-ERK1/2 pathway

Tensile load is known to regulate the osteogenesis of mesenchymal stem cells (MSCs) and osteogenic progenitors; therefore it is widely used in clinical treatment and tissue engineering. Meanwhile, in vitro, both published studies and our lab data demonstrate that the application of intermittent tensile loading which stimulates cells several minutes or hours each day for several days has promoted the osteogenic differentiation of MSCs. Whereas, for clinic trails, it is important to know accurately how and how long mechanical tension should be applied. Hence, it is necessary to investigate different kinds of mechanical tension on osteogenesis of MSCs. Until now, during the osteogenesis, there has been no research on the effect of continuous cyclic mechanical tension (CCMT) which provides continuous stimulation throughout the study period. We firstly figure out CCMT inhibiting the expression of osteogenic genes such as key transcription factor Runx2. It is known that RhoA regulates cell differentiation in response to mechanical stimuli. MAPK signaling acts as a downstream effector of RhoA. So, we ask in MSCs, if CCMT regulates the osteogenic master gene Runx2 through RhoA‐ERK1/2 pathway. And then, we find out there is a decrease in RhoA activity after CCMT stimulation. Pre‐treatment of CCMT‐loaded MSCs with LPA, a RhoA activator, restores ALP activity and significantly rescues Runx2 expression, while pre‐treatment with C3 toxin, a RhoA inhibitor, further decreases the activity of ALP and down‐regulates the expression of Runx2. Following results indicate that the inhibition of Runx2 expression after CCMT stimulation is mediated by RhoA‐ERK1/2 pathway. J. Cell. Physiol. 226: 2159–2169, 2011.

PCR-Based Diagnosis of Prosthetic Joint Infection

ABSTRACT We performed a meta-analysis to evaluate use of PCR assays for diagnosis of prosthetic joint infection (PJI). The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.77 to 0.92) and 0.91 (CI, 0.81 to 0.96), respectively. Subgroup analyses showed that use of tissue samples may improve sensitivity, and quantitative PCR and sonication of prostheses fluid may improve specificity. The results showed that PCR is reliable and accurate for detection of PJI.

Risk Factors for Periprosthetic Joint Infection after Total Hip Arthroplasty and Total Knee Arthroplasty in Chinese Patients

Purpose The purpose of this hospital-based case–control study was to evaluate the risk factors for periprosthetic joint infection (PJI) of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in Chinese patients. Method From January 2000 to December 2012, 45 patients undergoing THA and TKA who developed PJI were recruited for case subjects; controls were 252 without PJI, matched by year of index for surgery and type of surgery. Conditional logistic regressions were run to compute odds ratios (ORs) and 95% confidence intervals (CIs). Results Demographic factors and comorbid conditions associated with an increased adjusted risk of PJI (in decreasing order of significance) were diabetes (OR = 5.47, 95% CI: 1.77–16.97; p = 0.003), age (65–75 vs. 45–65 years) (OR = 3.36, 95% CI: 1.30–8.69; p = 0.013), BMI (≥28 vs. 18.5–28 kg/m2) (OR = 2.77, 95% CI: 1.20–6.40; p = 0.017), place of residence (rural) (OR = 2.63, 95% CI: 1.13–6.10; p = 0.025) and alcohol abuse (OR = 2.95, 95% CI: 1.06–8.23; p = 0.039). Conclusion Patients with diabetes, older age, BMI of ≥28 kg/m2 and alcohol abuse or living in rural areas, had increased PJI risk. Additional systematic large-scale studies are needed to verify these results.

Association Between Physical Activity and Risk of Fracture

Prospective studies that have examined the association between physical activity and fracture risks have reported conflicting findings. We performed a meta‐analysis to evaluate this association. We searched MEDLINE (1966 to February 1, 2013), EMBASE (1980 to February 1, 2013), and OVID (1950 to February 1, 2013) for prospective cohort studies with no restrictions. Categorical, heterogeneity, publication bias, and subgroup analyses were performed. There were 22 cohort studies with 1,235,768 participants and 14,843 fractures, including 8874 hip, 690 wrist, and 927 vertebral fractures. The pooled relative risk (RR) of total fractures for the highest versus lowest category of physical activity was 0.71 (95% confidence interval [CI], 0.63–0.80). The analysis of fracture subtypes showed a statistically significant inverse relationship between a higher category of physical activity and risk of hip and wrist fracture. The risk of hip or wrist fracture was 39% and 28% lower, respectively, among individuals with the highest category of physical activity than among those with the lowest category (95% CI, 0.54–0.69 and 0.49–0.96, respectively). The association between physical activity and vertebral fracture risk was not statistically related (RR, 0.87; 95% CI, 0.72–1.03). There was no evidence of publication bias. There was a statistically significant inverse association between physical activity and total fracture risk, especially for hip and wrist fractures. Additional subject‐level meta‐analyses are required for a more reliable assessment of subgroups and types of physical activity.

Preoperative Aspiration Culture for Preoperative Diagnosis of Infection in Total Hip or Knee Arthroplasty

ABSTRACT This meta-analysis evaluated preoperative aspiration culture for diagnosing prosthetic joint infection (PJI) in total hip arthroplasty (THA) and total knee arthroplasty (TKA). The pooled sensitivity and specificity were 0.72 (95% confidence interval, 0.65 to 0.78) and 0.95 (0.93 to 0.97), respectively. Subgroup analyses revealed nonsignificant worse diagnostic performance for THA than for TKA (sensitivity, 0.70 versus 0.78; specificity, 0.94 versus 0.96). Preoperative aspiration culture has moderate to high sensitivity and very high specificity for diagnosing PJI.