Association of TIMP4 gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern China

Background In clinical treatment, the use of steroid hormones is an important etiological factor of non-traumatic osteonecrosis of the femoral head (ONFH) risk. As an endogenous inhibitor of matrix metalloproteinases (MMPs) in the extracellular matrix, the expression of tissue inhibitors of metalloprotease-4 (TIMP4) plays an essential role in cartilage and bone tissue damage and remodeling, vasculitis formation, intravascular thrombosis, and lipid metabolism. Methods This study aimed to detect the association between TIMP4 polymorphism and steroid-induced ONFH. We genotyped seven single-nucleotide polymorphisms (SNPs) in TIMP4 genes and analyzed the association with steroid-induced ONFH from 286 steroid-induced ONFH patients and 309 normal individuals. Results We performed allelic model analysis and found that the minor alleles of five SNPs (rs99365, rs308952, rs3817004, rs2279750, and rs3755724) were associated with decreased steroid-induced ONFH (p = 0.02, p = 0.03, p = 0.04, p = 0.01, p = 0.04, respectively). rs2279750 showed a significant association with decreased risk of steroid-induced ONFH in the Dominant and Log-additive models (p = 0.042, p = 0.028, respectively), and rs9935, rs30892, and rs3817004 were associated with decreased risk in the Log-additive model (p = 0.038, p = 0.044, p = 0.042, respectively). In further stratification analysis, TIMP4 gene variants showed a significant association with steroid-induced ONFH in gender under the genotypes. Haplotype analysis also revealed that “TCAGAC” and “CCGGAA” sequences have protective effect on steroid-induced ONFH. Conclusion Our results indicate that five TIMP4 SNPs (rs99365, rs308952, rs3817004 rs2279750, and rs3755724) are significantly associated with decreased risk of steroid-induced ONFH in the population of northern China

Use of maternal health services among women in the ethnic rural areas of western China

Abstract Background The use of maternal health services can markedly promote the maternal health and safety, but there has been a low utilization rate in the ethnic rural areas of western China. Furthermore, the correlated factors have not been well studied. This study aims to assess factors related to the use of maternal health services among women in these areas. Methods A cross-sectional study of 68 villages in China’s western Sichuan province was conducted in September 2014. All qualifying women from each sample village were involved. A structured questionnaire was administrated in households through face-to-face interviews by trained enumerators to obtain information of use of maternal health services and related factors. Structural equation modeling (SEM) was used to evaluate the direct and indirect relationships between use of maternal health services and correlated factors. Results A total of 760 women from 68 villages were enrolled. The proportion of antenatal care (ANC), hospital delivery and postpartum visits were 68.94, 48.29 and 28.42% respectively. The SEM analysis demonstrated that social economic status (SES) (β= − 0.75, β< 0.01), ANC (β=0.13, β< 0.01), and time from home to the nearest hospital (β= − 0.09, β< 0.05), were positively correlated to hospital delivery and postpartum care visits, while maternal care knowledge and perceived quality of hospital care did not have direct correlation. For ANC, SES (β= − 0.36, β< 0.01), time from home to the nearest hospital (β= − 0.13, β< 0.05), knowledge on maternal care (β=0.12, β< 0.01) and perceived quality of hospital care (β=0.10, β< 0.01) were all directly correlated factors. Treating ANC as an intermediate variable showed the indirect relationship that perceived quality of hospital care (β=0.01, β< 0.01) and maternal care knowledge (β=0.02, β< 0.01) had with hospital delivery and postpartum care rates. Conclusions Use of maternal health services is low among women in ethnic rural areas. ANC has important direct and intermediate effects on subsequent use of hospital delivery and postpartum care. Improving ANC behavior should be a priority of maternal health care reforms. Given the long travel times for these women, reforms must also prioritize breaking down practical barriers that prevent this population from accessing care

MMP2 and MMP10 Polymorphisms Are Related to Steroid-Induced Osteonecrosis of the Femoral Head among Chinese Han Population

Background. Steroid-induced osteonecrosis of the femoral head is a relatively serious condition which seriously reduces patient quality of life. However, the pathogenesis of steroid-induced ONFH is still unclear. In recent years, more scholars have found that the pathogenesis of steroid-induced ONFH is related to susceptibility factors such as MMPs/TIMPs system. The main purpose of this study is to investigate the correlation between MMP2 and MMP10 gene polymorphisms and steroid-induced ONFH in Chinese Han population. Methods. Six SNPs in MMP2 and two SNPs in MMP10 were genotyped using Agena MassARRAY RS1000 system from 286 patients of steroid-induced ONFH and in 309 healthy controls. The association between MMP2 and MMP10 polymorphisms and steroid-induced ONFH risk were estimated by the Chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. The relative risk was estimated by odd ratios (ORs) and 95% confidence intervals (CIs). Result. We found that the minor TG allele of rs470154 in MMP10 was associated with an increased risk of steroid-induced ONFH (OR = 1.45, 95% CI, 1.03 – 2.05, p = 0.032). In the genetic model analysis, we found that rs2241146 in MMP2 gene and rs470154 in MMP10 gene showed a statistically significant association with increased risk of steroid-induced ONFH. The six SNPs (rs470154, rs243866, rs243864, rs865094, rs11646643, and rs2241146) showed a statistically significant association with different clinical phenotypes. Conclusion. Our results verify that genetic polymorphisms of MMP2 and MMP10 contribute to steroid-induced ONFH susceptibility in the population of Chinese Han population, and our study provides new insights into the role that MMP2 and MMP10 plays in the mechanism of ONFH

Analysis of the potential biological mechanisms of Danyu Gukang Pill against osteonecrosis of the femoral head based on network pharmacology

Abstract Background Osteonecrosis of the femoral head (ONFH) is still a challenge for orthopedists worldwide and can lead to disability if patients are not treated effectively. Danyu Gukang Pill (DGP), a traditional Chinese medicine (TCM) formulation, is recognized to be effective against ONFH. Nevertheless, its molecular mechanisms remain to be clarified. Methods The active ingredients of DGP were collected from the online databases according to oral bioavailability (OB) and drug-likeness (DL). The potential targets of DGP were retrieved from the TCMSP database, while the potential targets of ONFH were obtained from the GeneCards and NCBI databases. The functions and signaling pathways of the common targets of DGP and ONFH were enriched by GO and KEGG analyses. Subsequently, molecular docking and in vitro cell experiments were performed to further validate our findings. Results In total, 244 active ingredients of DGP and their corresponding 317 targets were obtained, and 40 ONFH-related targets were predicted. Afterwards, 19 common targets of DGP and ONFH were obtained and used as potential targets for the treatment of ONFH. Finally, combined with network pharmacology analysis, molecular docking and in vitro cell experiments, our study first demonstrated that the treatment effect of DGP on ONFH might be closely related to the two targets, HIF1A (HIF-1α) and VEGFA, and the HIF-1 signaling pathway. Conclusions This study is the first to investigate the molecular mechanisms of DGP in the treatment of ONFH based on network pharmacology. The results showed that DGP might up-regulate the expression of HIF-1α and VEGFA by participating in the HIF-1 signaling pathway, thus playing an anti-ONFH role

Polypyrrole-assisted oxygen electrocatalysis on perovskite oxides

Nitrogen-containing electrocatalysts, such as metal-nitrogen-carbon (M-N-C) composites and nitrogen-doped carbons, are known to exhibit high activities for an oxygen reduction reaction (ORR). Moreover, even if the mechanism by which nitrogen improves the activities is not completely understood, a strong electronic interaction between nitrogen and active sites has been found in these composites. Herein, we demonstrate a case in which nitrogen improves the electroactivity, but in the absence of a strong interaction with other components. The overpotentials of the ORR and oxygen evolution reaction (OER) on perovskite oxide catalysts were significantly reduced simply by mixing the catalyst particles with polypyrrole/carbon composites (pPy/C). Any strong interactions between pPy (a nitrogen-containing compound) and active sites of the catalysts are not confirmed. A scenario based on the sequential task allocation between pPy and oxide catalysts for the ORR was proposed: (1) molecular oxygen is incorporated into pPy as a form of superoxide (pPy(+)O(2)(-)), (2) the superoxide is transferred to the active sites of perovskite catalysts, and (3) the superoxide is completely reduced along the 4e ORR process.clos