Dongyang Chen

Association of the D repeat polymorphism in the ASPN gene with developmental dysplasia of the hip: a case-control study in Han Chinese

IntroductionDevelopmental dysplasia of the hip (DDH) is a common skeletal disease, which is characterized by abnormal seating of the femoral head in the acetabulum. Genetic factors play a considerable role in the etiology of DDH. Asporin (ASPN) is an ECM protein which can bind to TGF-β1 and sequentially inhibit TGF-β/Smad signaling. A functional aspartic acid (D) repeat polymorphism of ASPN was first described as an osteoarthritis-associated polymorphism. As TGF-β is well known as an important regulator in the development of skeletal components, ASPN may also be involved in the etiology of DDH. Our objective is to evaluate whether the D repeat polymorphism of ASPN is associated with DDH in Han Chinese.MethodsThe D repeat polymorphism was genotyped in 370 DDH patients and 445 control subjects, and the allelic association of the D repeat was examined.ResultsFrom D11 to D18, eight alleles were identified. D13 allele is the most common allele both in control and DDH groups, the frequencies are 67.3% and 58.1% respectively. In the DDH group, a significantly higher frequency of the D14 allele and significantly lower frequency of D13 was observed. The association of D14 and D13 was found in both females and males after stratification by gender. There was no significant difference in any other alleles we examined.ConclusionsOur results show an obvious association between the D repeat polymorphism of ASPN and DDH. It indicates that ASPN is an important regulator in the etiology of DDH.

Incidence of Symptomatic and Asymptomatic Venous Thromboembolism After Elective Knee Arthroscopic Surgery: A Retrospective Study With Routinely Applied Venography

PURPOSE The purpose of this study was to assess the incidence of total venous thromboembolism (VTE) after knee arthroscopy with routinely applied venography. METHODS We reviewed 537 consecutive patients undergoing arthroscopic knee surgery from March 2012 to July 2013. The surgical procedure was categorized as simple anterior cruciate ligament reconstruction (ACLR), posterior cruciate ligament reconstruction (PCLR), or reconstruction of both cruciate ligaments. All patients having arthroscopy in our institution were routinely examined with venography on the third postoperative day. Clinical signs of DVT were checked and recorded before venography. RESULTS Eighty (14.9%) of 537 patients were diagnosed with VTE by venography. Of the 80 detected cases of VTE, only 20 (3.7%) patients presented with clinical signs of DVT, indicating that there were 60 (11.2%) asymptomatic cases. No patient died or presented with a clinically suspected pulmonary embolism (PE). Sex, body mass index (BMI), operative time, and duration of tourniquet application were not significant risk factors for DVT. Patient age (P < .0001) is a strongly significant risk factor for deep venous thrombosis (DVT). Compared with patients who underwent simple arthroscopic procedures, complex procedures-the reconstruction of 1 (P < .005) or both knee cruciate ligaments (P < .0005)-led to a significantly higher postoperative incidence of DVT. CONCLUSIONS The total incidence of VTE diagnosed with venography after arthroscopic knee surgery was 14.9%, of which only 3.7% of cases were symptomatic, indicating 11.2% cases of silent VTE. Advanced age and complex arthroscopic surgery are strongly associated with VTE. LEVEL OF EVIDENCE Level IV, prognostic case series.

A panel of microRNAs as a new biomarkers for the detection of deep vein thrombosis

Abstract Deep vein thrombosis is one of the common complications of orthopedic surgery, and pulmonary embolism which is one of its lethal complications can lead to mortality. Numerous efforts have been made to identify reliable and predictive biomarkers to detect the early signs of deep vein thrombosis. These studies have, however, not delivered any more informative candidates than the D-dimer that have been available. Cell-free microRNAs are present in a range of body fluids and have recently been shown to be useful biomarkers in many diseases. Therefore, the purpose of present study was to identify potential microRNA biomarkers of deep vein thrombosis that are present in serum. Serum samples were taken from 18 deep vein thrombosis patients and 20 age- and sex-matched controls. TaqMan microRNA array was used for an initial screening. Real-time PCR assay was implemented to confirm the concentrations of candidate microRNAs. We found that the serum levels of miR-582, miR-195 and miR-532 of deep vein thrombosis patients were higher than those of controls. miR-582 yielded an AUC (the areas under the ROC curve) of 0.959, and the other two microRNAs yielded an AUC of 1.000 in discriminating deep vein thrombosis from controls. These data hint that serum miR-582, miR-195 and miR-532 might have potential to be a novel noninvasive biomarkers for detection of DVT. And this is the first study suggesting that serum microNRAs might be used as biomarkers for deep vein thrombosis.

Association of the aspartic acid-repeat polymorphism in the asporin gene with age at onset of knee osteoarthritis in Han Chinese Population

AbstractRecent genetic studies for osteoarthritis (OA) have been focused on ASPN, the gene encoding asporin, where aspartic acid (D)-repeat polymorphisms are associated with OA in several ethnic groups. The purpose of the present study is to further examine the association of the D-repeat polymorphism in a Han Chinese population. The D-repeat polymorphism was genotyped in 354 knee OA patients (257 women and 97 men) who suffered from primary symptomatic knee OA with radiographic confirmation, and the association of the repeat with various clinical parameters was examined. The age at onset (years) in patients with the D14 allele (mean: 51.9, SD: 8.5) was younger than that those without the D14 allele (mean: 54.9, SD: 10.9) (P = 0.023). Survival analysis showed D14 was significantly associated with age at onset of OA (P = 0.004 in the dominant model). The average age at onset of patients with the D13/D13 genotype (mean: 56.1, SD: 11.1) was older than those without the D13/D13 genotype (mean: 53.0, SD: 9.9) (P = 0.013). Our study further highlighted the significance of asporin in OA.

Biomarkers of deep venous thrombosis

Deep venous thrombosis (DVT), which is associated with pulmonary embolism, is a fatal disease because of its high morbidity and mortality in outpatients and inpatients, especially in hospitalized patients. At the same time, lack of subjective clinical symptoms and objective clinical signs makes the diagnosis complicated. Historically, the primarily imaging modalities, including duplex ultrasound, helical CT scans, and venography, establish the diagnosis of DVT. Currently, both imaging modalities and serology are utilized. These plasma molecules are regarded as the biomarkers of DVT including D-dimer, P-selectin, Factor VIII, thrombin generation, inflammatory cytokines, microparticles, fibrin monomer, leukocyte count and so on. This brief review is used to analyze the contribution of the biomarkers to diagnosis and guidance of therapy for DVT.

Deep Venous Thrombosis After Knee Arthroscopy: A Systematic Review and Meta-Analysis

PURPOSE To establish a contemporary literature-based estimate of the incidence of deep venous thrombosis (DVT) after knee arthroscopic surgery. METHODS We performed a systematic review and meta-analysis of the English language literature to assess the efficacy of prophylaxis to prevent DVT after knee arthroscopic surgery. Only randomized controlled trials (RCTs) or prospective studies were considered. Studies were excluded if they were not original prospective studies concerning DVT detected by imaging after knee arthroscopic surgery. We calculated pooled proportions of postoperative DVT and proximal DVT. RESULTS Nine prospective uncontrolled studies and 4 RCTs were retrieved. Within them, the populations given low-molecular-weight heparin (LMWH) to prevent DVT had a 0.1% to 11.9% incidence of DVT, with an overall 36 DVTs identified (4 proximal), averaging 1.8%. One hundred thirty-six DVTs (29 proximal) were indicated in the populations without prophylaxis, and the DVT incidence varied from 1.8% to 41.2%, averaging 6.8%. Of the RCTs, the pooled risk ratio for DVT to develop was 0.180 (range, 0.065 to 0.499) for those who had LMWH as prophylaxis. An absolute risk reduction of 1.2%--from 1.5% to 0.3%--for the development of proximal DVT was observed. CONCLUSIONS Compared with patients who did not receive prophylaxis, the pooled risk ratio for the development of DVT was 0.18 for those who had LMWH prophylaxis. The incidence of proximal DVT is very low after arthroscopic surgery regardless of receiving prophylaxis (4 of 2,184) or not (29 of 1,814). The rate of proximal DVT in total DVT occurrence can be markedly reduced from 21.3% (29 of 136) to 11.1% (4 of 36). LEVEL OF EVIDENCE Level IV. This study is a meta-analysis of RCTs and a systematic review of Level IV studies.

Intravenous release of NO from lipidic microbubbles accelerates deep vein thrombosis resolution in a rat model

OBJECTIVE The experiment was designed to analyze whether and how nitric oxide (NO) microbubbles facilitates deep vein thrombosis (DVT) resolution in a rat model. METHODS AND RESULTS DVT was induced by ligation of the inferior vena cava (IVC) and left common iliac vein (LCIV) in a rat model. The rats were sacrificed at day 2 and day 8 after ligation. NO was wrapped in lipidic microbubbles which were injected (1.6ml/kg) via tail vein twice a day. Thrombi isolated from IVC were measured by weight (g) and weight length ratio (g/cm).The histological analysis of LCIV indicated that platelets and inflammatory cells aggregation were reduced. The expression of vascular cell adhesion molecule-1 (VCAM-1) was quantified by immunohistochemical (IHC) staining and western blot. The coagulation functions including prothrombin time (PT), thrombin time (TT),activated partial thromboplastin time (APTT) and fibrinogen (FIB) were tested as well.Vein walls from IVC were processed by real-time polymerase chain reaction (RT-PCR) for several endothelial genes including matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), thrombomodulin (TM), and endothelial nitric oxide synthase (eNOS). The thrombus weight and the expression of VCAM-1 significantly decreased after NO microbubbles treatment. The expression of these endothelial genes were significantly up-regulated by NO micribubbles. There was no statistical difference among the groups in terms of PT, APTT, and TT. CONCLUSION NO microbubbles significantly facilitate DVT resolution in a rat model. The antithrombotic properties of NO microbubbles may be associated with reduced platelets and inflammatory cells aggregation, enhanced collagen turnover and stimulus to an anticoagulant condition of endothelium.

Lack of association between the CALM1 core promoter polymorphism (-16C/T) and susceptibility to knee osteoarthritis in a Chinese Han population

BackgroundCALM1 gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca2+-binding protein. Several studies have indicated that a deficient CaM function is likely to be involved in the pathogenesis of osteoarthritis (OA). Using a convincing genome-wide association study, a Japanese group has recently demonstrated a genetic association between the CALM1 core promoter polymorphism (-16C/T transition SNP, rs12885713) and OA susceptibility. However, the subsequent association studies failed to provide consistent results in OA patients of differently selected populations. The present study is to evaluate the association of the -16C/T polymorphism with knee OA in a Chinese Han population.MethodsA case-control association study was conducted. The polymorphism was genotyped in 183 patients who had primary symptomatic knee OA with radiographic confirmation and in 210 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects.ResultsNo significant difference was detected in genotype or allele distribution between knee OA and control groups (all P > 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the -16C/T SNP genotype and the clinical variables age, sex, BMI (body mass index) and K/L (Kellgren/Lawrence) score was observed in OA patients.ConclusionThe present study suggests that the CALM1 core promoter polymorphism -16C/T is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.

Association of Single Nucleotide Polymorphisms in Estrogen Receptor Alpha Gene with Susceptibility to Knee Osteoarthritis: A Case-Control Study in a Chinese Han Population

Osteoarthritis (OA) is the most prevalent form of arthritis and its multifactorial nature has been increasingly recognized. Genetic factors play an important role in OA etiology and estrogen receptor alpha (ESR1) gene polymorphisms may be involved. This study tried to explore whether the ESR1 gene single nucleotide polymorphisms (SNPs) were associated with primary knee OA in the Chinese Han population. Two SNPs, rs2234693 and rs9340799, were genotyped in 469 cases and 522 controls. Rs2234693 was associated with knee OA in the dominant genetic model (TT + TC versus CC) (P = 0.025) and a higher T allele frequency existed (P = 0.047) among females. The combined genotype (TT + TC) (P = 0.025) and T allele (P = 0.016) were related with mild knee OA only. For rs9340799, A allele was associated with knee OA in all subjects (P = 0.031) and females (P = 0.046). Statistical differences were detected in the dominant genetic model (AA + AG versus GG) among females (P = 0.030). The combined genotype (AA + AG) (P = 0.036) and A allele (P = 0.039) were merely correlated with mild knee OA. ESR1 gene is considerably associated with knee OA etiology in the Chinese Han population.

Application of an articulating spacer in two-stage revision for severe infection after total knee arthroplasty.

Objective:  To investigate the efficiency and safety of articulating spacer for severe infection after total knee arthroplasty (TKA) in patients with medical comorbidities and local sinus tracts.