The Effect of Common Variants in SLC44A2 on the Contribution to the Risk of Deep Cein Thrombosis after Orthopedic Surgery.

AIM: Deep vein thrombosis (DVT) is a common complication of orthopedic surgery. Multiple lines of evidence indicate that genetic factors play an important role in the development of DVT following orthopedic surgery (DVTFOS). Recent evidence suggested that the solute carrier family 44 member 2 (SLC44A) gene may contribute to the risk of DVT. In this study, we aimed to investigate the associations of SLC44A2 and DVTFOS in Chinese Han individuals. METHODS: In the study, 2,655 subjects, including 689 DVTFOS patients and 1,966 controls, were recruited. Eighteen SNPs were genotyped in the study. Genetic association analyses were performed at both the single marker and haplotype levels. Bioinformatics analyses were conducted to predict the functional consequences of significant SNPs. RESULTS: SNP rs2288904 of SLC44A2 was identified as being significantly associated with DVTFOS (P = 0.0003, OR [95%CI] = 1.28[1.12-1.46]). Allelic analyses showed that the G allele of this SNP significantly elevated the risks of DVTFOS, which was replicated in the genotypic association analyses. Moreover, a two-SNP haplotype, including rs2288904, was found to be strongly correlated with the risk of DVTFOS (P = 4.15×10－11). Widespread effects in the expression quantitative trait loci were identified for rs2288904 in multiple tissues. CONCLUSION: In summary, our results provide further supportive evidence of the association of SLC44A2 with the risk of DVTFOS, which also provide clues for understanding the important roles of the SLC44A2 gene in the pathogenesis of DVTFOS and in the development of preventive strategies.

The effects of common variants in MDM2 and GNRH2 genes on the risk and survival of osteosarcoma in Han populations from Northwest China.

Accumulating evidence has shown that both MDM2 and GNRH2 might be related to Osteosarcoma (OS) susceptibility. The study aimed to evaluate the effects of common variants in MDM2 and GNRH2 genes on the risk and survival of osteosarcoma in Han populations from Northwest China. In the study, we recruited 2292 subjects including 596 OS patients and 1696 healthy controls and genotyped 16 selected tag SNPs (6 from GNRH2 and 10 from MDM2). Genetic association analyses were performed at the genotypic and allelic levels. Survival curves were made for OS patients with different genotypes. Two SNPs, rs1690916 (MDM2, P = 0.0002) and rs3761243 (GNRH2, P = 0.0004), were identified to be significantly associated with OS risk. Moreover, SNP rs3761243 was strongly associated with pathological fracture (P = 2.61 × 10-14), metastasis (P < 2.2 × 10-16), and Enneking stage (P < 2.2 × 10-16) in the OS group. Furthermore, survival curves based on different genotypes of SNP rs3761243 were found to be significantly different (P = 0.0003), suggesting increased risk with more copies of C alleles. Our results provide supportive evidence for genetic associations of MDM2 and GNRH2 genes with susceptibility to OS, and for the positive correlation of SNP rs3761243 in GNRH2 with the survival status of OS patients in Han populations from Northwest China.

Balser Plate Stabilization for Traumatic Sternoclavicular Instabilities or Medial Clavicle Fractures: A Case Series and Literature Review.

OBJECTIVE: This study was performed to observe the effect of internal Balser plate fixation for treating unstable sternoclavicular joints (SCJ) and displaced medial clavicle fractures. METHODS: From April 2009 to September 2016, 17 consecutive patients who underwent open reduction and internal Balser plate fixation for SCJ dislocations or medial clavicle fractures were retrospectively reviewed. There were 11 male and six female patients, with a mean age of 45.6 ± 15.5 years. Standardized treatment procedures consisted of reduction, creating a space posterior dorsal osteal face of the sternal manubrium, an inverted Balser plating, and postoperative immobilization. At follow-up, plain radiographs were assessed for fracture union, implant loosening, degenerative changes, and joint congruity. Clinical evaluation included: completion of the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire; determination of the Constant and Murley score and visual analog scale (VAS) score; and assessment of intraoperative and postoperative complications. RESULTS: All patients were followed up, at a mean follow-up of 20.1 ± 7.9 months, each fracture had a solid union, and each dislocation showed no sign of recurrent dislocation. The mean shoulder forward flexion was 162.9° ± 8.1°. The mean DASH score was 5.2 ± 5.2 points. The mean Constant and Murley joint function score was 93.7 ± 7.9 points, with 15 excellent cases and two good cases. The mean VAS score was 1.1 ± 1.4 points, showing significant improvement compared with the VAS score preoperatively. Postoperative complications included one wound hematoma which was healed after a debridement and one recurrent instability due to hook migration, which underwent revision reconstruction. All patients were satisfied with their treatment outcome at the final follow-up. CONCLUSION: Sternoclavicular joints dislocation or medial clavicle fractures can be treated successfully with Balser plate fixation. This technique permits early functional exercise while preserving the SCJ.

Progranulin modulates cartilage-specific gene expression via sirtuin 1-mediated deacetylation of the transcription factors SOX9 and P65.

Progranulin (PGRN) is an autocrine growth factor that exerts crucial roles within cartilage tissue; however, the molecular mechanisms underlying PGRN-mediated cartilage homeostasis remain elusive. In the present study, we investigated the role of PGRN in regulating chondrocyte homeostasis and its therapeutic potential for managing osteoarthritis (OA). We found that PGRN levels are significantly increased in human cartilage in mild OA and that its expression is decreased in the cartilage in severe OA. In vitro, treatment of primary rat chondrocytes with recombinant PGRN significantly enhanced the levels of collagen type II α 1 chain (COL2A1) and aggrecan, and attenuated TNFα-induced up-regulation of matrix metallopeptidase 13 (MMP13) and ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) in chondrocytes. These effects were abrogated in SIRT1-/- cells, indicating a causative role of SIRT1 in the effects of PGRN on protein expression in chondrocytes. Mechanistically, PGRN increased SIRT1 expression and activity, which reduced the acetylation levels of SRY-box transcription factor (SOX9) and transcription factor P65 (P65) and thereby promoted nuclear translocation of SOX9 and inhibited TNFα-induced P65 nuclear accumulation to maintain chondrocyte homeostasis. In conclusion, our findings reveal a mechanism of action for PGRN that maintains cartilage homeostasis and supports the notion that PGRN up-regulation may be a promising strategy for managing OA.

Evaluation of genetic susceptibility of common variants in SOX9 in patients with congenital talipes equinovarus in the Han Chinese population.

BACKGROUND: Congenital talipes equinovarus (CTEV) is a common birth defect that causes severe deformities of one or both feet. Genetics have been proven to play a key role in the risk of CTEV. Our study aimed to evaluate the genetic susceptibility of common variants in the SOX9 gene to CTEV in a Han Chinese population. METHODS: In this study, we recruited 2,205 study participants, including 692 CTEV patients and 1513 healthy controls. A total of seven selected single-nucleotide polymorphisms (SNPs) within the SOX9 gene were genotyped, and environmental variables, including maternal smoking and alcoholic drinking habits, were assessed. In addition, bioinformatics analyses were performed to explore the potential biological functions of the associated SNPs. RESULTS: The SNP rs73354570 was identified to be significantly associated with the risk of CTEV (OR = 1.53, P = 2.11 × 10-5), and the C allele was associated with an increased risk of CTEV. A dose-dependent pattern could be observed in genotypic analyses. The OR for individuals with AC genotypes was 1.37 (95% CI 1.09-1.71), and the OR for individuals with CC homozygotes was 1.47 (95% CI 1.18-1.82). Further analyses identified that rs73354570 is located within a region of multiple binding proteins, including CEBPB and POLR2A, which suggested that this SNP was also part of genetic motifs that are found within several cell types. CONCLUSION: Our results provide evidence supporting the important role of the SOX9 gene in the contribution to the risk of CTEV.

[Treatment of aseptic ulnar diaphyseal nonunion with locking compression plate and autogenous iliac bone graft].

OBJECTIVE: To investigate the clinical results of locking compression plate combined with autologous iliac bone graft in the treatment of aseptic ulnar nonunion. METHODS: From March 2009 to July 2017, 22 patients with aseptic ulnar diaphyseal nonunion with complete follow-up data were treated with surgery, including 12 males and 10 females, aged from 16 to 58 (39.7±9.9) years old and ranging in course of disease from 10 to 192 (39.4±55.7) months. There were 15 atrophic nonunions, 5 hypertrophic nonunions and 2 synovial pseudo-articular nonunions. After debridement of the nonunion, locking compression plate was used to fix the nonunion and autogenous iliac bone graft was given. Bone healing rate, surgical complications and clinical results were evaluated. RESULTS: All the patients were followed up, and the duration ranged from 13 to 42 months, with a mean of (22.5±8.2) months, and 1 patient did not heal. Visual analogue pain scores ranged from 0 to 3 (0.9±0.9). Pronation of forearm was 47 to 86 (69.0±14.7) degrees, supination was 35 to 85 (63.0±9.4) degrees, wrist flexion was 20 to 80 (51.0±10.2) degrees, wrist flexion was 32 to 88 (71.0±11.7) degrees, elbow flexion contracture was 0 to 25 (9.0±5.6) degrees, further flexion was 105 to 150 (134.0±13.9) degrees, and grip strength was 87% on the opposite side. According to the Anderson scoring system, 8 cases were excellent, 11 were satisfied, 2 were not satisfied, and 1 was failed. CONCLUSIONS: LCP combined with autologous iliac bone graft can effectively treat aseptic ulna diaphyseal nonunion.