MTHFR C677T polymorphism, homocysteine, burden, and location of AMI and ACI.

OBJECTIVE: We aimed to investigate the relationship between homocysteine levels and MTHFR C677T polymorphisms and acute ischemic vascular events and focused on the differential effects of the MTHFR C677T polymorphisms on the burden and location of AMI and ACI. PATIENTS AND METHODS: 102 acute cerebral infarction (ACI) and acute myocardial infarction (AMI) patients who were admitted to the First Hospital of Jilin University in northeast China as the patient group, 83 healthy people who were hospitalized during the same period served as a control group. MTHFR C677T genotypes were identified via Polymerase Chain Reaction (PCR)-Fluorescent Probe Method. RESULTS: Patient group had higher serum homocysteine levels (p=0.013), lower serum folic acid (p<0.001), and Vit B12 levels (p=0.004) compared to the control group. Homocysteine levels in the patient group with the TT genotypes of the MTHFR C677T polymorphisms were higher than those with the CC and CT genotypes (p<0.05). Folic acid levels in the patients with TT genotypes were lower than those with the CC genotypes (p<0.05), but not in the control group (p>0.05). There were negative and significant associations between serum homocysteine levels and serum vitamin B12 levels in the control group (r=-0.234, p=0.033), but not between serum homocysteine levels and serum folic acid levels (r=-0.103, p=0.355). Conversely, there was a negative and significant association between serum homocysteine levels and serum folic acid levels in the patients' group (r=-0.257, p=0.01), but not between serum homocysteine levels and serum vitamin B12 levels (r=-0.185, p=0.64). No statistically significant differences in MTHFR C677T genotype and C/T alleles distribution were investigated between the patient and control group (p>0.05). The MTHFR C677T polymorphism did not differentially affect the burden and location of AMI and ACI. CONCLUSIONS: Homocysteine played a common role in atherosclerosis-related acute ischemic vascular events. These correlations were modified by MTHFR C677T polymorphisms and influenced by folic acid levels. The MTHFR C677T polymorphisms were not directly related to acute ischemic vascular events, nor did they differentially affect the burden and location of AMI and ACI.

Different subsets of haematopoietic cells and immune cells in bone marrow between young and older donors.

Young donors are reported to be associated with better transplant outcomes than older donors in allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the mechanism is still unclear. The current study compared the different subsets of haematopoietic stem cells (HSCs) and their progenitors as well as immune cells in bone marrow (BM) between young and older donors. The frequencies of HSCs, multipotent progenitors (MPPs) and myeloid progenitors, including common myeloid progenitors (CMPs) and megakaryocyte-erythroid progenitors (MEPs), were decreased, whereas those of lymphoid progenitors, including multi-potent lymphoid progenitors (MLPs) and common lymphoid progenitors (CLPs), were increased in the BM of young donors compared with in that of older donors. Lower reactive oxygen species (ROS) levels were observed in BM HSCs and six progenitor lines in young donors. Furthermore, young donors demonstrated higher frequencies of naive T cells and immune suppressor cells, such as alternative macrophages (M2) and lower frequencies of memory T cells and immune effectors, including T helper-1 and T cytotoxic-1 cells, in BM than older donors. Multivariate analysis demonstrated that donor age was independently correlated with BM HSC frequency. Although further validation is required, our results suggest that the differences in the frequency and immune differentiation potential of HSCs in BM between young donors and older donors may partly explain the different outcomes of allo-HSCT.

Effect of bone marrow mesenchymal stem cells on perforator skin flap survival area in rats.

Trans-territory perforator flaps are commonly used to reconstruct large defects of the soft tissues. The distal portion of the flap often becomes necrotic, however, as a result of the jeopardised vasculature of choke zone II. The trophic and vascular regenerative properties of bone marrow mesenchymal stem cells (BMSC) seemed to be a promising approach to prevent flaps becoming ischaemic. The purpose of our study is to evaluate the effects of BMSC on the survival of the three-territory perforator flap. The flap model was created based on the deep circumflex iliac vessel in rats. Eighteen rats were distributed, at random, into three groups. Immediately after the flaps were placed, groups were respectively given a single panniculus carnosus injection at choke zone II of either 1×105 (BMSCslow), 1×106 (BMSCshig) BMSC, or phosphate-buffered saline (PBS). On postoperative day seven, we assessed the gross view of the flap and survival. We also evaluated microvessels by histological examination and angiogenesis-related gene expression by quantitative real-time polymerase chain reaction. After high dosage of BMSC, the flap survival rate, diameter and density of microvessels, vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) levels were significantly higher in the BMSC treatment group than the control group. We therefore confirmed the positive effects of BMSC on the survival of multi-territory perforator flaps.

LncRNA ANRIL regulates cell proliferation and migration via sponging miR-339-5p and regulating FRS2 expression in atherosclerosis.

OBJECTIVE: Atherosclerosis (AS), with high risk of stroke or cerebrovascular disease, is one of the most common causes of death worldwide. Increasing evidence shows that long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) is related to atherothrombotic stroke susceptibility and contributes to AS progression. However, the underlying mechanism was not explained yet. PATIENTS AND METHODS: Human aorta vascular smooth muscle cells (HA-VSMCs) and human umbilical vein endothelial cells (HUVECs) were treated with oxidized Low Density Lipoprotein (ox-LDL) and considered as AS cell models. Quantitative reverse transcriptase PCR (qRT-PCR) and Western blotting were employed to investigate the mRNA and protein expression level, respectively. Microscopic examination through fluorescent in situ hybridization (FISH) was used to determine the location of ANRIL. Cell proliferation and migration assays were demonstrated to evaluate the functional role of ANRIL in AS. Potential target of ANRIL was determined using Luciferase reporter assay and RNA immunoprecipitation (RIP). RESULTS: ANRIL was upregulated and miR-399-5p was down-regulated in both human atherosclerotic plaques and ox-LDL-induced cells. ANRIL was located in cytoplasm and promoted cell proliferation and migration by sponging miR-399-5p. Further analysis identified fibroblast growth factor receptor substrate 2 (FRS2) as a direct target of miR-399-5p. Finally, RAS/RAF/ERK signal pathway was proved to be involved in the regulation of ANRIL on the progression of AS. CONCLUSIONS: These results revealed the underlying mechanism that ANRIL promoted AS progression by sponging miR-399-5p and regulating RAS/RAF/ERK signal pathway, suggesting that ANRIL might be a potential target for the therapeutic strategy of AS.

MiR-373 promotes the osteogenic differentiation of BMSCs from the estrogen deficiency induced osteoporosis.

OBJECTIVE: This study aimed to investigate the expression of miR-373 in osteoporosis patients and rat models induced by estrogen deficiency and to detect whether miR-373 can regulate the ability of osteogenic differentiation of bone marrow mesenchymal stem cells in the osteoporosis microenvironment caused by estrogen deficiency. PATIENTS AND METHODS: Bone tissues and blood samples were collected from 20 osteoporotic patients and 20 controls. PCR analysis was used to detect the expression of miR-373 in bone tissue and serum from postmenopausal osteoporotic patients and normal patients. 120 SD rats were purchased and randomly divided into sham operation group and OVX group. Rat models of sham-operated and bilateral oophorectomy mice models were constructed. The expression of miR-373 in bone tissue, cells, and serum of the mice was tested. Then, bone marrow mesenchymal stem cells from sham-operated rats and bilaterally ovariectomized rats were isolated and cultured. After 10 days of osteogenic induction, alkaline phosphatase staining and alizarin red staining were performed to test the osteogenic differentiation ability of bone marrow mesenchymal stem cells, and whether miR-373 affects this ability. RESULTS: PCR results showed that the expression of miR-373 in the bone tissue and the serum of patients with postmenopausal osteoporosis was significantly reduced. The expression of miR-373 was markedly decreased in the bone tissue, cells, and serum from the rats of bilateral ovariectomy group. Alkaline phosphatase staining and alizarin red staining showed that miR-373 could promote the differentiation of bone marrow mesenchymal stem cells into osteoblasts and reverse the decreased osteogenic differentiation of bone marrow mesenchymal stem cells caused by osteoporosis. CONCLUSIONS: The expression of miR-373 is decreased in osteoporotic patients and rat models caused by estrogen deficiency, and it can promote the differentiation of bone marrow mesenchymal stem cells into the osteogenic direction. This work provides a new direction and experimental basis for clinical diagnosis and treatment of osteoporosis.

Melatonin protects methotrexate-induced testicular injury in rats.

OBJECTIVE: Melatonin possesses anti-inflammation and anti-oxidant potentials. However, whether NF-E2 related factor 2 (Nrf2) pathway and nuclear factor-kappaB (NF-κB) pathway are involved in the protective effect of melatonin are unknown. We aim to explore the regulatory effect of melatonin on methotrexate-induced testicular injury. MATERIALS AND METHODS: Sprague Dawley (SD) rats were randomly assigned in sham group, methotrexate group and melatonin group, with 8 rats in each group. Testis tissues were collected 10 days after animal procedures. Pathological lesions and cell apoptosis in testis tissues were evaluated using HE (hematoxylin and eosin) staining and TUNEL assay, respectively. Oxidative stress in rat testis was accessed using relative commercial kits. Western blot was performed to detect protein expressions of relative genes in Nrf2 pathway and NF-κB pathway in rat testis tissues. RESULTS: Activities of SOD, GSH, CAT and T-AOC in testis homogenate in melatonin group were remarkably higher than those of methotrexate group (p < 0.05). On the contrary, levels of MDA, ROS and inflammatory factors (TNF-α, IL-1ß, IL-6 and KC-GRO) were markedly decreased after melatonin treatment. Besides, melatonin group showed alleviated pathological lesions and cell apoptosis in testis. Western blot results demonstrated that melatonin treatment upregulated expressions of Nrf2, GSR, GCLm, HO-1 and NQO-1 in testis. However, protein expressions of NF-κB, TNF-α, VCAM-1, ICAM-1 and MCP-1 were downregulated. CONCLUSIONS: Melatonin protects methotrexate-induced testicular damage in rats by improving antioxidant capacity and inhibiting inflammatory response via Nrf2 and NF-κB pathways.

Comparison of pharmacodynamic effects of ticagrelor vs prasugrel in type 2 diabetes mellitus patients with coronary heart disease.

WHAT IS KNOWN AND OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of thrombotic complications. Studies have indicated that patients with T2DM have impaired clopidogrel-induced antiplatelet effect. Ticagrelor and prasugrel are two latest generation P2Y12 inhibitors with advantageous platelet inhibitory profiles. However, the pharmacodynamic differences between the two drugs in patients with T2DM remain poorly explored. METHODS: This study, involving 140 patients with T2DM following percutaneous coronary intervention (PCI), evaluated the efficacy of aspirin upon concomitant use of prasugrel (10 mg/d) or ticagrelor (90 mg/d). Platelet reactivity was assessed by value of ADP-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at baseline, 7 and 30 days after randomized P2Y12 inhibitor treatment. RESULTS: The study showed a decreased platelet reactivity after use of P2Y12 inhibitors (both P < .001). On the basis of comparison between regimens, apart from the prasugrel group having a significantly higher LTA value at the 30-day time point (P = .043), there existed no significant differences in platelet reactivity at separate time points (all P > .05). As for intragroup measurements, when compared with 7-day and 30-day time points, similar platelet reactivity was documented in the ticagrelor group (both P > .05), but LTA tests showed a significant increase with time (days 7-30) in the prasugrel group (P = .050). WHAT IS NEW AND CONCLUSION: Although ticagrelor and prasugrel have similar platelet inhibitory effects in patients with T2DM, if a P2Y12 inhibitor is necessitated in patients with T2DM, ticagrelor might exert a more stable antiplatelet effect with 30-day short-term treatment.

Association between osteocalcin and glucose metabolism: a meta-analysis.

UNLABELLED: This meta-analysis aimed to investigate the associations between osteocalcin (Ocn) and fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c). It was revealed that both total Ocn and undercarboxylated Ocn (unOcn) were negatively related with FPG and HbA1c, and the association of unOcn with FPG was more pronounced in men. INTRODUCTION: The aim of this study was to investigate the strength of associations between Ocn and FPG and HbA1c using a meta-analysis approach. METHODS: A search was carried out using the databases of PubMed, ISI Web of Science, and the Cochrane library from 2007 to 2014 to identify related studies. A pooled effect size with 95 % confidence intervals (CI) was derived. RESULTS: The meta-analysis included 39 studies involving 23,381 participants. The overall correlation was -0.16 (95 % CI, -0.19 to -0.14) between total Ocn (tOcn) and FPG and -0.15 (95 % CI, -0.20 to -0.11) between undercarboxylated Ocn (unOcn) and FPG. In the analysis of the association between Ocn and HbA1c, the pooled correlation was -0.16 (95 % CI, -0.18 to -0.14) for tOcn and -0.16 (95 % CI, -0.23 to -0.08) for unOcn. The magnitude of the correlation between unOcn and FPG is significantly higher in men than in women (r = -0.18, 95 % CI, -0.21 to -0.14; r = -0.09, 95 % CI, -0. 13 to -0.05, respectively; P for interaction < 0.05). Similar trend was also found between unOcn and HbA1c but without significance (for men, r = -0.19, 95 % CI, -0.24 to -0.14; for women, r = -0.09, 95 % CI, -0.22 to 0.04, respectively; P for interaction > 0.05). No indication of significant publication bias was found in any method. CONCLUSIONS: This meta-analysis demonstrated that both unOcn and tOcn were similarly and negatively correlated with FPG and HbA1c in humans. The negative correlations between unOcn and glucose metabolism appear to be more pronounced in men than in women.

Meta-analysis of the cytotoxic T-lymphocyte antigen 4 gene +6230G/A polymorphism and cancer risk

OBJECTIVES: Cytotoxic T-lymphocyte antigen-4 (CTLA4, CD152) is one of the most fundamental immunosuppressive cytokines that inhibits T-cell activation and terminates the T-cell response by blocking signals stimulated via CD28. A number of studies have assessed the association between CTLA-4 +6230G/A polymorphism and cancer risk. However, the results remain controversial. METHODS: In the present study, we performed a meta-analysis to derive a more precise estimation of the relationship. A comprehensive literature search was performed using the PubMed database for relevant articles published (updated to November 21, 2013). Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the association. RESULTS: A total of 13 articles with 14 studies were selected for this meta-analysis, including 4,489 cases and 4,715 controls. Combined analysis revealed no associations between CTLA-4 +6230G/A polymorphism and cancer risk. However, in stratified analysis by cancer type, we found that CTLA-4 +6230G/A polymorphism was associated with the risk of breast cancer (AA vs. AG + GG: OR = 0.77, 95 % CI 0.60-0.97, P = 0.03; AA vs. GG: OR = 0.66, 95 % CI 0.46-0.95, P = 0.02) and cervical cancer (AA vs. AG + GG: OR = 0.56, 95 % CI 0.42-0.75, P < 0.01). Additionally, in subgroup analysis based on ethnicity, significant association was also found between the CTLA-4 +6230G/A polymorphism and cancer risk in the Asian population (AA vs. AG + GG: OR = 0.71, 95 % CI 0.59-0.84, P < 0.01). CONCLUSION: This meta-analysis indicates that CTLA-4 +6230G/A polymorphism may be associated with a decreased risk of breast cancer and cervical cancer in Chinese population (AU)

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Meta-analysis of the cytotoxic T-lymphocyte antigen 4 gene +6230G/A polymorphism and cancer risk.

OBJECTIVES: Cytotoxic T-lymphocyte antigen-4 (CTLA4, CD152) is one of the most fundamental immunosuppressive cytokines that inhibits T-cell activation and terminates the T-cell response by blocking signals stimulated via CD28. A number of studies have assessed the association between CTLA-4 +6230G/A polymorphism and cancer risk. However, the results remain controversial. METHODS: In the present study, we performed a meta-analysis to derive a more precise estimation of the relationship. A comprehensive literature search was performed using the PubMed database for relevant articles published (updated to November 21, 2013). Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the association. RESULTS: A total of 13 articles with 14 studies were selected for this meta-analysis, including 4,489 cases and 4,715 controls. Combined analysis revealed no associations between CTLA-4 +6230G/A polymorphism and cancer risk. However, in stratified analysis by cancer type, we found that CTLA-4 +6230G/A polymorphism was associated with the risk of breast cancer (AA vs. AG + GG: OR = 0.77, 95 % CI 0.60-0.97, P = 0.03; AA vs. GG: OR = 0.66, 95 % CI 0.46-0.95, P = 0.02) and cervical cancer (AA vs. AG + GG: OR = 0.56, 95 % CI 0.42-0.75, P < 0.01). Additionally, in subgroup analysis based on ethnicity, significant association was also found between the CTLA-4 +6230G/A polymorphism and cancer risk in the Asian population (AA vs. AG + GG: OR = 0.71, 95 % CI 0.59-0.84, P < 0.01). CONCLUSION: This meta-analysis indicates that CTLA-4 +6230G/A polymorphism may be associated with a decreased risk of breast cancer and cervical cancer in Chinese population.

Pharmacokinetics of florfenicol in crucian carp (Carassius auratus cuvieri) after a single intramuscular or oral administration.

The pharmacokinetics of florfenicol (FF) was studied in plasma after a single dose (40 mg/kg) of intramuscular (i.m.) or oral gavage (p.o.) administration to crucian carp (Carassius auratus cuvieri) in freshwater at 25 °C. Ten fish per sampling point were examined after treatment. The data were fitted to two-compartment open models follow both routes of administration. The estimates of total body clearance (CL(b) ), volume of distribution (V(d) /F), and absorption half-life (T(1/2(ka)) ) were 0.067 L/h/kg and 0.145 L/h/kg, 2.21 L/kg and 1.04 L/kg, 2.75 and 1.54/h following i.m. and p.o. administration, respectively. After i.m. injection, the elimination half-life (T(1/2(ß)) ) was calculated to be 38.2h, the maximum plasma concentration (C(max) ) to be 16.82 µg/mL, the time to peak plasma FF concentration (T(max) ) to be 1.50 h, and the area under the plasma concentration-time curve (AUC) to be 597.4 µg/mL·h. Following p.o. administration, the corresponding estimates were 2.17 h, 29.32 µg/mL, 1.61 h, and 276.1 µg/mL·h.

Application of chromatography technology in the separation of active components from nature derived drugs.

Chromatography technology has been widely applied in various aspects of the pharmacy research on traditional Chinese medicine (TCM). This paper reviews literatures, published in the past decades, on the separation of active component from TCM using chromatography technology. Ultra-performance liquid chromatography (UPLC), high-speed counter-current chromatography (HSCCC), rapid resolution liquid chromatography (RRLC), supercritical fluid chromatography (SFC), affinity chromatography (AC), and bio-chromatography (BC) are introduced in detail. Compared to high performance of high-performance liquid chromatography (HPLC), analysis time and solvent loss are significantly reduced by UPLC with increase in resolution and sensitivity. Some ingredients from nature derived drugs can be separated more completely by HSCCC, which has remarkable characteristics such as low cost, simple operation and no pollution. Trace components from complex systems can be selectively and efficiently separated and purified by AC, This feature makes it effective in isolation and identification of active components of Chinese herbs. Interference of some impurities could be excluded by BC. Active ingredients that are difficult to be separated by normal method can be acquired by SFC. Currently, application of novel chromatography techniques in TCM is still in the exploratory stage and many problems, such as preparation of stationary phase and detection, need to be solved.

Overexpression of AIB1 negatively affects survival of surgically resected non-small-cell lung cancer patients.

BACKGROUND: The amplified in breast cancer 1 (AIB1) gene has been considered to play an oncogenic role in human cancers, but its clinical/prognostic significance in non-small-cell lung cancer (NSCLC) is still unclear. PATIENTS AND METHODS: The methods of immunohistochemistry and FISH were utilized to examine protein expression and amplification of AIB1 in 230 informative surgically resected NSCLCs and in 30 samples of normal lung tissues. RESULTS: Overexpression and amplification of AIB1 were found in 48.3% and 8.2% of NSCLCs, respectively. AIB1 overexpression was associated with AIB1 gene amplification and cell proliferation but not related to estrogen receptor (ER)-alpha, ER-beta, progesterone receptor or androgen receptor status. A positive correlation between AIB1 overexpression and an ascending pathologic node stage in lung adenocarcinoma (ADC) was observed (P = 0.043). Univariate survival analysis demonstrated a significant association of AIB1 overexpression with shortened patient survival, especially for those with stage III disease (P < 0.001). Importantly, AIB1 expression was evaluated as the most significant predictor for survival in multivariate analysis (hazards ratio = 2.069, P < 0.001). CONCLUSION: Overexpression of AIB1 might provide a selective advantage for lymph node metastasis of lung ADC and serve as a useful biomarker for poor prognosis for NSCLC patients.

Phase I and biodistribution study of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene and ganciclovir administration in patients with head and neck cancer and other malignant tumors.

In this study, we investigated the safety and efficacy in cancer patients of a single intra-tumor injection of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene (AdV/TK) followed by systemic administration of ganciclovir (GCV). In 18 patients with malignant tumors refractory to standard treatment, AdV/TK was injected on day 1 with dose escalation from 2.5 x 10(11) to 1 x 10(12) virus particles (VP), and GCV (5 mg kg(-1)) was delivered intravenously every 12 h from days 2 to 15. The most common treatment-related toxicities were transient fever (10/18) and local injection site reaction (10/18), and most adverse events were WHO grade I/II. Anti-adenovirus antibody levels increased continuously during treatment, but anti-HSV antibody levels remained stable. One patient had a PR at the injection site but PD was found in the primary site (lung cancer), one patient with fibrosarcoma of the neck had an MR, five patients had SD, and 10 patients had PD. In conclusion, AdV/TK followed by GCV can be administered safely to Chinese cancer patients, and achieved a local response with few environmental effects. Because the response was localized, single regional tumor relapse, especially after radiation, may be an indication for this suicide gene therapy.

Comparison between cells and cancer stem-like cells isolated from glioblastoma and astrocytoma on expression of anti-apoptotic and multidrug resistance-associated protein genes.

This study is to explore and compare the features of the cells and cancer stem-like cells (CSCs) isolated from both glioblastoma and astrocytoma on expression of anti-apoptotic and multidrug resistance-associated protein (MRP) genes. As a result, the mRNA expression of livin, livinalpha and MRP1 was up-regulated in human CSCs from 2 times to 85 times, but the gene expression of MRP3 was down-regulated from 0.09 times to 0.5 times. After just differentiation the mRNA expression of livin, livinalpha and MRP3 was up-regulated from 9 times to 64 times, but the mRNA expression of MRP1 was down-regulated from 0.01 times to 0.03 times. It is a rare report that glioma stem-like cells can be induced successfully from a grade 2-3 astrocytoma tissue. The properties of glioblastoma and astrocytoma stem-like cells on anti-apoptotic and MRP genes are: anti-apoptotic gene livin and survivin are elevated in CSCs but are the most increased in just differentiated CSCs; MRP1 gene is significantly increased and MRP3 is decreased in CSCs, but when differentiating the MRP3 gene starts a remarkable increase in CSCs; the expression of anti-apoptotic and MRP genes shows no differences between the CSCs isolated from glioblastoma and astrocytoma tissues.

Relationships between insulin-like growth factor-I (IGF-I) and OPG, RANKL, bone mineral density in healthy Chinese women.

UNLABELLED: Serum IGF-I level was negatively correlated with OPG and OPG/RANKL ratio, but positively correlated with RANKL. Serum OPG level in the highest quintile of IGF-I was significantly lower than that in the lowest. We conclude that the effect of IGF-I on bone remodeling may be mediated by the OPG/RANKL system. INTRODUCTION: Insulin-like growth factor I (IGF-I) is an important factor in coupling bone remodeling, activating both formation and resorption. Compared with the many studies on the role of IGF-I in bone formation, the information regarding its effects on bone resorption is limited and conflicting. The balance of the two peptides produced by osteoblasts, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL), is critical for the bone resorption process. Our study was designed to analyze the relationships of serum concentrations of IGF-I with OPG, RANKL, OPG/RANKL ratio as well as BMDs in healthy Chinese women. METHODS: BMDs at lumbar spine and proximal femur in 504 pre- and postmenopausal women were measured by DXA. Serum levels of IGF-I, OPG and RANKL were also measured. Pearson's correlation and partial correlation analysis, ANOVA, covariance analysis and stepwise multiple regression analysis were used as appropriate. RESULTS: Age was negatively correlated with serum levels of IGF-I (r = -0.702, p < 0.001). IGF-I was negatively correlated with OPG and OPG/RANKL ratio, but positively correlated with RANKL. The relationship between IGF-I and BMDs disappeared after adjustment for age. In postmenopausal women, IGF-I was lower in women with osteoporosis than in those with normal BMD (p = 0.056), but no differences were found among OPG, RANKL and OPG/RANKL ratio. Serum levels of OPG in the highest quintile of IGF-I were significantly lower than those in the lowest quintile of IGF-I, while no difference was found in RANKL. In the multiple regression analysis model, serum levels of IGF-I were the main determinants of the bone mass in Chinese women. CONCLUSIONS: In conclusion, the relationship between decreasing IGF-I and BMDs in healthy Chinese women influenced by age, whereas the effect of IGF-I on bone remodeling (bone resorption) may be mediated by the OPG/RANKL system.