Mei Wei

To determine the concentration of quercetin in mouse plasma by HPLC-DAD in different time after oral administration with Gualou Xiebai decoction and Gualou decoction, and to explore the influence of the compatibility of Gualou and Xiebai on pharmacokinetics of quercetin in Gualou. The plasma sample was simply deproteinized with acetonitrile, extracted three times by aceticether, evaporated to dryness with a gentle N2 stream, dissolved with methanol and determined by HPLC. The pharmacokinetic parameters were separately calculated and compared with data processing software DAS 2. 0 and SPSS 11. 5 software. After oral administration with Gualou Xiebai decoction and Gualou decoction, the pharmacokinetics of quercetin in mouse plasma accorded with the two-compartment model, and t1/2α, t1/2β, AUC0-t, AUC0-∞, Cmax, tmax, Ka, K10, K12, K21, CL/F and V1/F all had significant differences(P <0. 05 or P <0. 01). Xiebai in Gualou Xiebai decoction has a remarkable effect on pharmacokinetic character of quercetin in Gualou, it can promote the absorption and distribution and reduce the elimination of quercetin, in vivo, as well as increase the bioavailability of quercetin.

Stem cell-based tissue engineering for large bone defect healing has attracted enormous attention in regenerative medicine. However, sufficient osseointegration of the grafts combined with exogenous stem cells still remains a major challenge. Here, we developed a material approach to modulate the integration of the grafts to the host tissue when exogenous bone marrow stromal cells (BMSCs) were used as donor cells. Distinctive osseointegration of bone grafts was observed as we varied the content of hydroxyapatite (HA) in the tissue scaffolds implanted in a mouse femur model. More than 80% of new bone was formed in the first two weeks of implantation in high HA content scaffolds but host integration was poor, while only less than 5% of the new bone was formed during this time period in the No HA group but the host integration was good. Cell origin analysis leveraging the GFP reporter indicates new bone in the HA containing groups was mainly derived from donor BMSCs. In comparison, both host and donor cells were found on the new bone surface in the No HA groups which led to seamless bridging between host tissue and the scaffold. Most importantly, host integration during bone formation is closely dictated by the content of HA present in the scaffolds. Taken together, we demonstrate a material approach to modulate the osseointegration of bone grafts in the context of an exogenous stem cell-based bone healing strategy which might lead to fully functional bone tissue regeneration.

Parathyroid hormone (PTH) is a well-known therapeutic agent for osteoporosis treatment, however, the inconvenience of daily administration and side effect from systematic administration severely limits its application in clinic. PTH has been incorporated into a biomimetic calcium phosphate (CaP) coating via a co-precipitation method in a modified simulated body fluid. The aim of the current study is to evaluate the osseointegration response of PTH incorporated CaP coating on titanium implants. Implants with different doses of PTH were inserted into tibiae of mice and evaluated by X-ray, micro-CT, histology and back-scattered scanning electron microscopy. Improved osseointegration of the implants loaded with PTH was observed compared to CaP coating only after 28 days of implantation in mouse tibiae. Micro-CT analysis showed better bone integration around the implant incorporated with PTH. Bone area and bone contact evaluations have demonstrated that peri-implant bone regeneration is highly dependent on the dosage of PTH incorporated. The higher the PTH content, the more bone formed surrounding the implant. Therefore, our results suggest that biomimetic CaP coating could be a useful a carrier for PTH local delivery, which results in improved bone-to-implant integration.

To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA). Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed. In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P<0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P<0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P<0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD. The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.

To investigate the current status of tumor necrosis factor (TNF) inhibitors application in rheumatoid arthritis (RA) patients in China and to analyze the related factors. A retrospective survey was conducted in 21 hospitals from different parts of China. The patients with RA were randomly enrolled. Data of their social backgrounds, clinical conditions, usage and adverse effects of TNF inhibitors were collected. The costs of TNF inhibitors and the indirect costs of the disease were calculated. A multivariate Logistic regression analysis was performed to analyze the factors related to TNF inhibitors application. In the study, 1 095 RA patients from July 2009 to November 2010 were enrolled, of whom 112 had received TNF inhibitors, representing 10.2% of the total patients. The patients who received etanercept and infliximab were 7.4% (86/1 095) of the patients and 2.4% (26/1 095), respectively. There were 0.5% of the patients (5/1 095) who had received both of the TNF inhibitors. The patients who had accepted etanercept and treatment duration for less than 3 months and 3-6 months accounted for 38.5% and 25.0% respectively, while those treated with Infliximab were 38.1%. Their health assessment questionnaire (HAQ) scores were 1.1, 0.5 and 0.1, corresponding to treatment duration of infliximab for less than 3, 3-6 and 6-9 months and those were 1.3, 1.0, 0.3 corresponding to treatment duration of etanercept, respectively. Infliximab costs were RMB 24 525.0, 69 300.0 and 96 800.0 Yuan and etanercept costs were RMB 7 394.8, 9 158.6, 54 910.9 Yuan, respectively. Indirect costs for RA patients who accepted infliximab for less than 3, 3-6 and 6-9 months were RMB 365.6, 0 and 158.9 Yuan and those who accepted etanercept were RMB 2 158.4, 288.5 and 180.1 Yuan, respectively. Allergy and infection were the main side-effects of etanercept and both happened in 3.5% of all the patients. Liver damage happened in 2.3% of all the patients, while allergy and infection happened in 6.5% of all the patients who accepted infliximab. Logistic regression analysis showed that patients with higher education experience increased the odds of entering the TNF inhibitors group (OR: 1.292, 95%CI: 1.132-1.473, P=0.000). About one-tenth of RA patients in China have accepted TNF inhibitors. Higher education experience is the key factor for using TNF inhibitors.

To investigate the medication status of rheumatoid arthritis (RA) patients and to analyze the clinical use of sulphasalazine (SSZ) and the adverse effect. A total of 1 096 outpatients and inpatients diagnosed with RA were investigated in 21 hospitals all over China from July 2009 to December 2010, including gender, age of onset, clinical manifestations, as well as the clinical characteristics and medication status of 160 RA patients who received SSZ therapy. In the group of 160 patients who received SSZ, the male-to-female ratio was 1:7, The average age at onset was (46.1±15.0) years, while the average course was (9.9±7.8) years. The average dose of sulphasalazine was (1.87±0.52) g/d for a mean duration of (26.3± 14.6) months. Only 17% (27/160) of the patients received SSZ monotherapy. Methotrexate (63.1%), leflunomide (36.2%) and hydroxychloroquine (18.1%) were most commonly used combination drugs. And 36.2% (58/160) of the patients used the two-drug combination of methotrexate plus sulphasalazine .In this group, 41.9% (67/160) once used SSZ but withdrew for adverse events and other reasons, while 17.5% (28/160) withdrew for adverse events, of which the most common were gastrointestinal (8.8%), skin (3.8%) and liver toxicity (3.1%). Sulphaszlazine is not a common choice in the RA therapeutics in China, and the average dose of SSZ is lower than the standard dose of 2 to 3 g/d . The adverse events of SSZ are common; however, there are few severe adverse events or threat to life,SSZ is relatively safe in clinical practice.

Scaffold architecture has exhibited significant impact on bone tissue regeneration; however, few studies have tried to address the relationship between scaffold architecture and structural organization of newly generated bones. The aim of this study was to investigate the effect of scaffold architecture on the structural organization of a newly formed bone using a two-hole mouse calvarial defect model. Evaluation of bone formation indicated although the new bone was formed in both types of scaffolds, their structure was closely related to the microstructure of scaffolds. Both micro-CT and histology data have shown that, morphologically, cortical-like bone was formed in the lamellar scaffold (LS) group while trabecular-like bone was found in the cellular scaffold (CS) group. This finding expands the understanding of the role of scaffold architecture during bone regeneration. Moreover, early stage bone formation was observed in defects filled with LS regardless of donor cell types at day 14 while no bone formation was found in the CS group. In addition, when calvarial osteoprogenitor cells (OPCs) and bone marrow stromal cells (BMSCs) were used as the donor cells respectively, it was found that BMSCs not only induced better host integration by recruiting more host cell infiltration, but also better supported bone marrow and vascularization reconstruction in the defects. These results collectively suggest that the scaffold structure design strongly dictates the structural organization of the new bone which may eventually influence the bone healing outcome.